Worldwide evidence

ClinicalTrials.gov · 2027 · NCT07803250 · ClinicalTrials.gov

This registered human pilot trial will compare BPC-157 with placebo for tendon healing and functional recovery after rotator cuff repair surgery. It is not yet recruiting, and no results are reported.

Population / model

Rotator Cuff Tear

Citation: University of Arkansas. Impact of BPC-157 on Recovery From Rotator Cuff Repair Surgery. ClinicalTrials.gov 2027.

Sports Medicine · 2026 · PMID 41966639 · BioNex Evolve (PubMed-indexed)

This review examined peptide safety and effectiveness for musculoskeletal injuries and athletic performance, drawing on animal findings and available human evidence. Many unapproved peptides showed favorable tissue repair and metabolic outcomes in animals, but rigorous human safety data were scarce and there was potential for serious harm.

Citation: Mendias CL, Awan TM. Safety and Efficacy of Approved and Unapproved Peptide Therapies for Musculoskeletal Injuries and Athletic Performance.. Sports Medicine 2026.

The American Journal of Sports Medicine · 2026 · PMID 41476424 · BioNex Evolve (PubMed-indexed)

This review examined injectable peptides for orthopaedic injuries and sports medicine using laboratory, animal, and human research. BPC-157, TB-4, and TB-500 showed tissue-repair potential mainly in preclinical studies, while human evidence was limited or lacking. The authors concluded that evidence remains insufficient to support clinical use and that further safety and effectiveness research is needed.

Citation: Mayfield CK, Bolia IK, Feingold CL, Lin EH, Liu JN, Rick Hatch GF. Injectable Peptide Therapy: A Primer for Orthopaedic and Sports Medicine Physicians.. The American Journal of Sports Medicine 2026.

International journal of molecular sciences · 2026 · PMID 41898733 · BioNex Evolve (PubMed-indexed)

This review examined BPC-157 for tissue repair and pain, drawing mainly on animal and laboratory research plus small human pilot studies. Preclinical studies reported improved healing and reduced inflammation, while human studies suggested potential benefit without reported major adverse effects. The authors emphasized that limited human evidence and inconsistent preparation standards require rigorous controlled trials.

Citation: Yuan C, Demers A, Silva-Ortiz V, Hasoon JJ, Lee W, Dave K, Amirdelfan K, Burke HW, Christo PJ, Robinson CL. From Regeneration to Analgesia: The Role of BPC-157 in Tissue Repair and Pain Management. International journal of molecular sciences 2026.

Pharmaceutics · 2026 · PMID 42198317 · BioNex Evolve (PubMed-indexed)

This review examined barriers to developing BPC-157 as a medicine, drawing on animal research and limited human pilot studies. It found that how the peptide behaves in humans remains poorly characterized, and no pharmaceutical-grade formulation has been developed or validated. Available human evidence came from small, uncontrolled studies, with no completed phase II trial.

Citation: Mateescu DM, Gavrilescu DM, Constantinescu FE, Oancea C, Ilie AC, Folescu R, Popa MD, Iurciuc S, Muresan CO, Enache A. BPC-157 as an Investigational Peptide Therapeutic: Biopharmaceutical Challenges, Formulation Strategies, and Translational Development Barriers. Pharmaceutics 2026.

Scientific reports · 2026 · PMID 42204242 · BioNex Evolve (PubMed-indexed)

This animal study tested BPC-157 in male rats with leg muscle injury caused by interrupted and then restored blood flow. BPC-157 reduced markers of oxidative stress, inflammation, and cell death, and improved muscle tissue structure. The findings suggest protective effects, but further research is needed to establish clinical relevance.

Citation: Yıldırım AK, Demirtaş H, Özer A, Arslan M. Protective effects of BPC 157 in rats with experimentally induced lower extremity ischemia-reperfusion injury. Scientific reports 2026.

Pharmaceuticals (Basel, Switzerland) · 2026 · PMID 41901308 · BioNex Evolve (PubMed-indexed)

This review examined BPC-157 as a way to protect blood vessels and address both bleeding and blood clots, relying largely on animal research. In rodents, BPC-157 could counteract both problems without directly affecting the blood-clotting process. The authors emphasized that these preclinical findings need further clinical validation.

Citation: Sikiric P, Barisic I, Udovicic M, Lovric Bencic M, Balenovic D, Strinic D, Posilovic GZ, Uzun S, Vranes H, Krezic I, Lozic M, Stambolija V, Premuzic Mestrovic I, Oreskovic LB, Kalogjera L, Strbe S, Sikiric S, Tomic L, Stupnisek M, Kordic M, Tvrdeic A, Seiwerth S, Boban Blagaic A, Skrtic A. Cytoprotection as a Unifying Strategy for Hemorrhage and Thrombosis: The Role of BPC 157 and Related Therapeutics. Pharmaceuticals (Basel, Switzerland) 2026.

Pharmaceuticals (Basel, Switzerland) · 2026 · PMID 41754849 · BioNex Evolve (PubMed-indexed)

This review examined platelet-rich plasma, growth factors, and BPC-157 for injuries to tendons, ligaments, muscles, and their attachment points. The BPC-157 findings described came from animal studies in rats, which consistently reported improved healing across these tissues and junctions. The authors called for further clinical studies.

Citation: Matek D, Matek I, Japjec M, Matek M, Prenc J, Staresinic B, Staresinic E, Prtoric A, Sikiric S, Beketic Oreskovic L, Oreskovic I, Strbe S, Kordic M, Tvrdeic A, Seiwerth S, Sikiric P, Boban Blagaic A, Skrtic A, Bojanic I, Dobric I, Staresinic M. Tendon, Ligament, and Muscle Injury, Osteotendinous, Myotendinous, and Muscle-to-Bone Junction Therapy Perspectives with Growth Factors and Stable Gastric Pentadecapeptide BPC 157-A Review. Pharmaceuticals (Basel, Switzerland) 2026.

Pharmaceuticals (Basel, Switzerland) · 2026 · PMID 41754776 · BioNex Evolve (PubMed-indexed)

This review explored cell protection as a way to assess heart rhythm medicines, including BPC-157 evidence from rodent experiments and laboratory-grown cells. It reported that BPC-157 counteracted several rhythm disturbances in animals and stabilized electrical properties in cells. The authors stated that limited human evidence needs expansion to test this proposed approach.

Citation: Sikiric P, Barisic I, Udovicic M, Lovric Bencic M, Balenovic D, Strinic D, Zivanovic Posilovic G, Uzun S, Vranes H, Krezic I, Lozic M, Stambolija V, Premuzic Mestrovic I, Beketic Oreskovic L, Oreskovic I, Strbe S, Sikiric S, Tomic L, Kordic M, Tvrdeic A, Seiwerth S, Boban Blagaic A, Skrtic A. Conventional Antiarrhythmics Class I-IV, Late INa Inhibitors, IKs Enhancers, RyR2 Stabilizers, Gap Junction Modulators, Atrial-Selective Antiarrhythmics, and Stable Gastric Pentadecapeptide BPC 157 as Useful Cytoprotective Therapy in Arrhythmias. Pharmaceuticals (Basel, Switzerland) 2026.

Joint diseases and related surgery · 2026 · PMID 42542926 · BioNex Evolve (PubMed-indexed)

This animal study tested BPC-157, TB-500, and their combination after Achilles tendon injury and repair in rats. Both peptides were associated with improved tendon tissue organization, but only TB-500 significantly increased the force tendons could withstand before breaking; BPC-157's overall tissue scores were not significantly improved. Combining the peptides provided no additional benefit.

Citation: Biçer O, Adanir O, Güleryüz Y, Balci EC, Dinçel YM, Yenigün MY, Aydin C, Bayrak BY. Effects of BPC-157 and TB-500 on Achilles tendon healing in rats: A histopathological and biomechanical study.. Joint diseases and related surgery 2026.

ClinicalTrials.gov · 2026 · NCT07437547 · ClinicalTrials.gov

This recruiting human trial is designed to compare investigational BPC-157 with placebo, alongside rehabilitation, in people with an acute partial hamstring tear confirmed by MRI. It will assess return to unrestricted sport and changes in injury size on MRI. No results are provided.

Population / model

Hamstring Muscle Strain; Skeletal Muscle Injury

Citation: Hudson Biotech. A Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial of Pentadecapeptide BPC 157 for Accelerated Repair of Acute Grade II Hamstring Strain Confirmed by MRI. ClinicalTrials.gov 2026.

Journal of the American Academy of Orthopaedic Surgeons. Global research & reviews · 2026 · PMID 41490200 · PubMed

This review examined peptides, including BPC-157, for bone, joint, and muscle injuries, drawing on preclinical research rather than established human trial evidence. It describes effects on tissue repair, inflammation, and recovery pathways. The authors characterize the preclinical findings as promising but emphasize the current lack of clinical trials.

Citation: Rahman OF, Lee SJ, Seeds WA. Therapeutic Peptides in Orthopaedics: Applications, Challenges, and Future Directions.. Journal of the American Academy of Orthopaedic Surgeons. Global research & reviews 2026.

Frontiers in aging · 2026 · PMID 42021992 · PubMed

This review examined human clinical and preclinical evidence on peptides targeting aging-related changes, including BPC-157 for tissue repair. Investigational peptides showed promising preclinical and limited clinical evidence but lacked long-term safety data and systematic validation. The authors conclude that rigorous clinical trials are needed to establish their safety and effectiveness for extending healthy life.

Citation: Mavrych V, Shypilova I, Bolgova O. Therapeutic peptides in gerontology: mechanisms and applications for healthy aging.. Frontiers in aging 2026.

Pharmaceuticals (Basel) · 2025 · PMID 40005999 · BioNex Evolve (PubMed-indexed)

This literature and patent review examined BPC-157's biological effects, possible mechanisms, and potential toxicity, drawing on preclinical models rather than established human benefits. It described beneficial effects in models of tissue injury, inflammatory bowel disease, and brain disorders. The review noted that sufficient, comprehensive clinical studies confirming health benefits in humans are lacking.

Citation: Józwiak M, Bauer M, Kamysz W, Kleczkowska P. Multifunctionality and Possible Medical Application of the BPC 157 Peptide-Literature and Patent Review.. Pharmaceuticals (Basel) 2025.

HSS Journal · 2025 · PMID 40756949 · BioNex Evolve (PubMed-indexed)

This systematic review examined BPC-157 for musculoskeletal injuries, mainly through animal and lab research, with limited human evidence. Preclinical studies reported improved muscle, tendon, ligament, and bone healing outcomes, while some patients in a retrospective knee-pain study reported relief. No clinical safety data were found, and the review noted possible harms from unregulated manufacturing, contamination, or unknown human safety.

Citation: Vasireddi N, Hahamyan H, Salata MJ, Karns M, Calcei JG, Voos JE. Emerging Use of BPC-157 in Orthopaedic Sports Medicine: A Systematic Review.. HSS Journal 2025.

Pharmaceuticals (Basel, Switzerland) · 2025 · PMID 40573323 · BioNex Evolve (PubMed-indexed)

This review discussed animal and laboratory research on BPC 157, tissue healing, blood vessel growth, and nitric oxide signaling. The authors reported protective effects in healing and animal models of Parkinson’s-like and Alzheimer’s-like disorders, alongside anti-tumor effects in animals and laboratory experiments. These findings do not establish benefits in humans.

Citation: Sikiric P, Seiwerth S, Skrtic A, Staresinic M, Strbe S, Vuksic A, Sikiric S, Bekic D, Soldo D, Grizelj B, Novosel L, Beketic Oreskovic L, Oreskovic I, Stupnisek M, Boban Blagaic A, Dobric I. Stable Gastric Pentadecapeptide BPC 157 as a Therapy and Safety Key: A Special Beneficial Pleiotropic Effect Controlling and Modulating Angiogenesis and the NO-System. Pharmaceuticals (Basel, Switzerland) 2025.

Pharmaceuticals (Basel, Switzerland) · 2025 · PMID 41471311 · BioNex Evolve (PubMed-indexed)

This review proposed a framework linking corneal healing, abnormal blood vessel growth, and eye pressure, drawing on preclinical research including rat studies. It reported that BPC-157 normalized elevated eye pressure, preserved corneal transparency during healing, and counteracted abnormal vessel growth. The authors encouraged further research toward human clinical use.

Citation: Masnec S, Kokot A, Kralj T, Zlatar M, Loncaric K, Sablic M, Kalauz M, Beslic I, Oroz K, Mrvelj B, Beketic Oreskovic L, Oreskovic I, Strbe S, Staresinic B, Slivsek G, Boban Blagaic A, Seiwerth S, Skrtic A, Sikiric P. Challenge of Corneal Ulcer Healing: A Novel Conceptual Framework, the "Triad" of Corneal Ulcer Healing/Corneal Neovascularization/Intraocular Pressure, and Avascular Tendon Healing, for Evaluation of Corneal Ulcer Therapy, Therapy of Neovascularization, Glaucoma Therapy, and Pentadecapeptide BPC 157 Efficacy. Pharmaceuticals (Basel, Switzerland) 2025.

Pharmaceuticals (Basel, Switzerland) · 2025 · PMID 40573261 · BioNex Evolve (PubMed-indexed)

This review examines animal studies of drugs for dangerously elevated pressure inside the abdomen and related organ damage. It reports that BPC-157 rapidly activated alternative blood-flow routes and counteracted damage across multiple organs, blood clots, and blood pressure disturbances. These findings concern animal research, not demonstrated benefits in humans.

Citation: Sikiric P, Seiwerth S, Skrtic A, Staresinic M, Strbe S, Vuksic A, Sikiric S, Bekic D, Penovic T, Drazenovic D, Becejac T, Tepes M, Madzar Z, Novosel L, Beketic Oreskovic L, Oreskovic I, Stupnisek M, Boban Blagaic A, Dobric I. Acute Compartment Syndrome and Intra-Abdominal Hypertension, Decompression, Current Pharmacotherapy, and Stable Gastric Pentadecapeptide BPC 157 Solution. Pharmaceuticals (Basel, Switzerland) 2025.

Medicina (Kaunas, Lithuania) · 2025 · PMID 40005408 · BioNex Evolve (PubMed-indexed)

This animal study examined whether BPC-157 protected the liver, kidneys, and lungs in male rats after blood flow to the legs was interrupted and restored. BPC-157 reduced tissue damage in these distant organs and increased antioxidant activity. The authors concluded that it had a significant protective effect in this rat model.

Citation: Demirtaş H, Özer A, Yıldırım AK, Dursun AD, Sezen ŞC, Arslan M. Protective Effects of BPC 157 on Liver, Kidney, and Lung Distant Organ Damage in Rats with Experimental Lower-Extremity Ischemia-Reperfusion Injury. Medicina (Kaunas, Lithuania) 2025.

Current reviews in musculoskeletal medicine · 2025 · PMID 40789979 · BioNex Evolve (PubMed-indexed)

This review assessed BPC-157 for muscle, tendon, and related tissue healing, drawing mainly on animal studies and very limited human research. It reported tissue-repair and protective effects in preclinical studies, while small human pilot studies reported no adverse effects. The authors emphasized that rigorous human trials are lacking and BPC-157 remains investigational.

Citation: McGuire FP, Martinez R, Lenz A, Skinner L, Cushman DM. Regeneration or Risk? A Narrative Review of BPC-157 for Musculoskeletal Healing.. Current reviews in musculoskeletal medicine 2025.

ClinicalTrials.gov · 2025 · NCT07752381 · ClinicalTrials.gov

This human trial record describes a study of BPC-157-containing gummies in physically active adults, examining blood markers of inflammation and self-reported physical performance and muscle and joint recovery. It is marked completed, but no results are provided.

Population / model

Musculoskeletal Inflammation; Exercise-Induced Muscle Damage; Post-Exercise Recovery; Musculoskeletal Pain

Citation: Parlay Wellness. A Clinical Trial to Evaluate the Effects of Peptide Gummies on Markers of Inflammation, Physical Performance, and Recovery. ClinicalTrials.gov 2025.

Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association · 2025 · PMID 39265666 · PubMed

This review discussed injectable peptides, particularly BPC-157, for injury recovery and sports performance. It describes very early research in living organisms, without specifying the species in the abstract, suggesting potential effects on recovery and tissue repair. The authors emphasize that clinical evidence for tendon, muscle, and cartilage injuries is scarce and highlight safety, ethical, and legal concerns.

Citation: DeFoor MT, Dekker TJ. Injectable Therapeutic Peptides-An Adjunct to Regenerative Medicine and Sports Performance?. Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association 2025.

Pharmaceuticals (Basel, Switzerland) · 2024 · PMID 39204186 · BioNex Evolve (PubMed-indexed)

This review examines animal studies of BPC-157 in rats with surgically reconnected digestive tissues and abnormal connections between organs or skin. It reports healing of these connections and improvement in associated disturbances, including inflammation and impaired intestinal function. The findings do not establish effectiveness in humans.

Citation: Bajramagic S, Sever M, Rasic F, Staresinic M, Skrtic A, Beketic Oreskovic L, Oreskovic I, Strbe S, Loga Zec S, Hrabar J, Coric L, Prenc M, Blagaic V, Brcic K, Boban Blagaic A, Seiwerth S, Sikiric P. Stable Gastric Pentadecapeptide BPC 157 and Intestinal Anastomoses Therapy in Rats-A Review. Pharmaceuticals (Basel, Switzerland) 2024.

Pharmaceuticals (Basel, Switzerland) · 2024 · PMID 38675421 · BioNex Evolve (PubMed-indexed)

This review explored possible links between BPC-157’s reported protective effects and nerve-signaling chemicals; the abstract does not specify the study populations. The authors describe evidence that BPC-157 counteracts disturbances in several signaling systems. They acknowledge that direct, conclusive evidence establishing BPC-157 as a neurotransmitter is lacking.

Citation: Sikiric P, Boban Blagaic A, Strbe S, Beketic Oreskovic L, Oreskovic I, Sikiric S, Staresinic M, Sever M, Kokot A, Jurjevic I, Matek D, Coric L, Krezic I, Tvrdeic A, Luetic K, Batelja Vuletic L, Pavic P, Mestrovic T, Sjekavica I, Skrtic A, Seiwerth S. The Stable Gastric Pentadecapeptide BPC 157 Pleiotropic Beneficial Activity and Its Possible Relations with Neurotransmitter Activity. Pharmaceuticals (Basel, Switzerland) 2024.

Journal of physiology and pharmacology : an official journal of the Polish Physiological Society · 2024 · PMID 38583442 · BioNex Evolve (PubMed-indexed)

This animal study tested BPC 157 in rats with surgically created abnormal connections between the small intestine and colon. All treated rats had closure of both openings, no leakage or diarrhea, and less internal scarring and intestinal blockage. Rapid recovery of blood vessels appeared to be important for healing.

Citation: Vukusic D, Zenko Sever A, Sever M, Drmic D, Milavic M, Sikiric S, Rasic D, Krezic I, Gojkovic S, Prtoric A, Bubalo P, Coric L, Dobric I, Boban Blagaic A, Rasic Z, Skrtic A, Seiwerth S, Sikiric P. Duodenocolic fistula healing by pentadecapeptide BPC 157 in rats. A cytoprotection viewpoint. Journal of physiology and pharmacology : an official journal of the Polish Physiological Society 2024.

Pharmaceuticals (Basel, Switzerland) · 2023 · PMID 37513963 · BioNex Evolve (PubMed-indexed)

This review discusses animal studies of BPC-157 in rats with experimentally induced glaucoma and other eye injuries. It reports immediate normalization of elevated eye pressure, preservation of retinal and optic nerve structures, and recovery of pupil function. Benefits were also reported for reduced retinal blood supply and corneal injuries, but human effectiveness was not established.

Citation: Sikiric P, Kokot A, Kralj T, Zlatar M, Masnec S, Lazic R, Loncaric K, Oroz K, Sablic M, Boljesic M, Antunovic M, Sikiric S, Strbe S, Stambolija V, Beketic Oreskovic L, Kavelj I, Novosel L, Zubcic S, Krezic I, Skrtic A, Jurjevic I, Boban Blagaic A, Seiwerth S, Staresinic M. Stable Gastric Pentadecapeptide BPC 157-Possible Novel Therapy of Glaucoma and Other Ocular Conditions. Pharmaceuticals (Basel, Switzerland) 2023.

World journal of gastroenterology · 2023 · PMID 37545637 · BioNex Evolve (PubMed-indexed)

This animal study examined BPC-157 in rats with a perforated stomach and severe blood vessel and organ dysfunction. BPC-157 reduced bleeding, clotting, abnormal blood pressures, and injury across multiple organs while promoting contraction of the stomach defect. The findings were from an acute rat experiment, not a human trial.

Citation: Kalogjera L, Krezic I, Smoday IM, Vranes H, Zizek H, Yago H, Oroz K, Vukovic V, Kavelj I, Novosel L, Zubcic S, Barisic I, Beketic Oreskovic L, Strbe S, Sever M, Sjekavica I, Skrtic A, Boban Blagaic A, Seiwerth S, Sikiric P. Stomach perforation-induced general occlusion/occlusion-like syndrome and stable gastric pentadecapeptide BPC 157 therapy effect. World journal of gastroenterology 2023.

Pharmaceuticals (Basel, Switzerland) · 2023 · PMID 37242459 · BioNex Evolve (PubMed-indexed)

This review explored whether BPC-157 may support communication between the brain and gut, drawing on animal experiments, including rat studies. It described improvements in behavioral models, muscle healing, and heart function, along with reduced brain and other organ injuries. The authors proposed that these effects may reflect interconnected actions across brain, gut, and blood-vessel systems.

Citation: Sikiric P, Gojkovic S, Krezic I, Smoday IM, Kalogjera L, Zizek H, Oroz K, Vranes H, Vukovic V, Labidi M, Strbe S, Baketic Oreskovic L. Stable Gastric Pentadecapeptide BPC 157 May Recover Brain-Gut Axis and Gut-Brain Axis Function.. Pharmaceuticals (Basel, Switzerland) 2023.

Life sciences · 2022 · PMID 36228773 · BioNex Evolve (PubMed-indexed)

This animal and laboratory study tested BPC 157 against radiation-induced liver injury in mice and cultured rat liver cells. BPC 157 reduced liver injury, cell death, and fat accumulation while increasing a protein called KLF4. Reducing KLF4 in the cultured cells abolished protection against cell death and fat accumulation.

Citation: Huang BS, Huang SC, Chen FH, Chang Y, Mei HF, Huang HY, Chen WY, Pang JS. Pentadecapeptide BPC 157 efficiently reduces radiation-induced liver injury and lipid accumulation through Kruppel-like factor 4 upregulation both in vivo and in vitro. Life sciences 2022.

Biomedicines · 2022 · PMID 36359218 · BioNex Evolve (PubMed-indexed)

This review discussed BPC-157 in heart and blood vessel research, including animal studies in rats with blocked vessels. It reported reduced clotting, heart rhythm disturbances, and organ injury, alongside recruitment of alternative blood flow pathways. These findings do not establish effectiveness in humans.

Citation: Sikiric P, Udovicic M, Barisic I, Balenovic D, Zivanovic Posilovic G, Strinic D, Uzun S, Sikiric S, Krezic I, Zizek H, Yago H, Gojkovic S, Smoday IM, Kalogjera L, Vranes H, Sola M, Strbe S, Koprivanac A, Premuzic Mestrovic I, Mestrovic T, Pavic P, Skrtic A, Blagaic AB, Lovric Bencic M, Seiwerth S. Stable Gastric Pentadecapeptide BPC 157 as Useful Cytoprotective Peptide Therapy in the Heart Disturbances, Myocardial Infarction, Heart Failure, Pulmonary Hypertension, Arrhythmias, and Thrombosis Presentation. Biomedicines 2022.

Neural regeneration research · 2022 · PMID 34380875 · BioNex Evolve (PubMed-indexed)

This review summarizes animal research on BPC-157 in rat models of stroke, drug-induced movement and behavioral disturbances, and spinal cord injury. It reports reduced brain damage, improved memory and movement, and improved healing and function after spinal cord compression. These findings concern animal models rather than demonstrated benefits in humans.

Citation: Vukojevic J, Milavić M, Perović D, Ilić S, Čilić AZ, Đuran N, Štrbe S, Zoričić Z, Filipčić I, Brečić P, Seiverth S, Sikirić P. Pentadecapeptide BPC 157 and the central nervous system.. Neural regeneration research 2022.

Biomedicines · 2022 · PMID 36551977 · BioNex Evolve (PubMed-indexed)

This review discusses BPC-157 research on skeletal, smooth, and heart muscle, including animal studies of injuries in rats. It describes recovery of injured muscle–tendon connections and suggests that BPC-157 might help restore impaired muscle, heart, and sphincter function. These findings do not establish benefits in humans.

Citation: Staresinic M, Japjec M, Vranes H, Prtoric A, Zizek H, Krezic I, Gojkovic S, Smoday IM, Oroz K, Staresinic E, Dretar V, Yago H. Stable Gastric Pentadecapeptide BPC 157 and Striated, Smooth, and Heart Muscle.. Biomedicines 2022.

Frontiers in Pharmacology · 2021 · PMID 34267654 · BioNex Evolve (PubMed-indexed)

This review discusses BPC-157 and wound healing, including animal studies of skin and other tissue injuries in rats. It reports healing of skin wounds and abnormal connections between tissues, alongside changes in blood vessels and clot resolution. These animal findings do not establish wound-healing benefits in humans.

Citation: Seiwerth S, Milavic M, Vukojevic J, Gojkovic S, Krezic I, Vuletic LB. Stable Gastric Pentadecapeptide BPC 157 and Wound Healing.. Frontiers in Pharmacology 2021.

Alternative Therapies in Health and Medicine · 2021 · PMID 34324435 · BioNex Evolve (PubMed-indexed)

This small retrospective human study reviewed knee injections of BPC-157, alone or combined with thymosin-beta-4, for different causes of knee pain. Most patients reached by telephone reported pain relief. The study lacked a control group and did not use standardized measures of function or quality of life.

Citation: Lee E, Padgett B. Intra-Articular Injection of BPC 157 for Multiple Types of Knee Pain.. Alternative Therapies in Health and Medicine 2021.

Behavioural brain research · 2021 · PMID 32956773 · BioNex Evolve (PubMed-indexed)

This animal study tested BPC-157 in rats with drug-induced movement disturbances used to model some schizophrenia-like symptoms. BPC-157 counteracted abnormal movement, rigid immobility, and increased responsiveness after repeated methamphetamine exposure. Its effects persisted when nitric oxide signaling was blocked or overstimulated; clinical applications remain to be determined.

Citation: Zemba Cilic A, Zemba M, Cilic M, Balenovic I, Strbe S, Ilic S, Vukojevic J, Zoricic Z, Filipcic I, Kokot A, Drmic D, Blagaic AB, Tvrdeic A, Seiwerth S, Sikiric P. Pentadecapeptide BPC 157 counteracts L-NAME-induced catalepsy. BPC 157, L-NAME, L-arginine, NO-relation, in the suited rat acute and chronic models resembling 'positive-like' symptoms of schizophrenia. Behavioural brain research 2021.

Scientific reports · 2020 · PMID 33051481 · BioNex Evolve (PubMed-indexed)

This animal-tissue and cell laboratory study examined how BPC-157 affects blood vessel relaxation. BPC-157 relaxed isolated rat aortas through a nitric oxide-dependent process involving the vessel lining. The findings suggest that it stimulates nitric oxide production through the Src–Caveolin-1–eNOS signaling pathway.

Citation: Hsieh MJ, Lee CH, Chueh HY, Chang GJ, Huang HY, Lin Y, Pang JS. Modulatory effects of BPC 157 on vasomotor tone and the activation of Src-Caveolin-1-endothelial nitric oxide synthase pathway. Scientific reports 2020.

Brain and behavior · 2020 · PMID 32558293 · BioNex Evolve (PubMed-indexed)

This animal study tested BPC 157 in rats after temporary blockage and restoration of blood flow to the brain. BPC 157 counteracted early and delayed damage in the hippocampus, a memory-related brain region. Treated rats achieved full functional recovery on tests of memory, movement, and coordination.

Citation: Vukojević J, Vrdoljak B, Malekinušić D, Siroglavić M, Milavić M, Kolenc D, Boban Blagaić A, Batelja L, Drmić D, Seiverth S, Sikirić P. The effect of pentadecapeptide BPC 157 on hippocampal ischemia/reperfusion injuries in rats. Brain and behavior 2020.

Drug design, development and therapy · 2020 · PMID 33376304 · BioNex Evolve (PubMed-indexed)

This animal study examined BPC 157 in rats with clopidogrel-induced recurrence of healed stomach ulcers. BPC 157 reduced stomach lining damage and reversed molecular changes linked to inflammation, cell death, and impaired blood vessel growth. Blocking nitric oxide signaling weakened these protective effects.

Citation: Wu H, Wei M, Li N, Lu Q, Shrestha SM, Tan J, Zhang Z, Wu G, Shi R. Clopidogrel-Induced Gastric Injury in Rats is Attenuated by Stable Gastric Pentadecapeptide BPC 157. Drug design, development and therapy 2020.

Current pharmaceutical design · 2020 · PMID 32445447 · BioNex Evolve (PubMed-indexed)

This review discusses BPC-157 and damage to digestive tract cells and tissues caused by nonsteroidal anti-inflammatory drugs (NSAIDs); the abstract does not specify the species studied. It describes potential protective actions against increased gut permeability, or “leaky gut,” following NSAID exposure.

Citation: Park JM, Lee HJ, Sikiric P, Hahm KB. BPC 157 Rescued NSAID-cytotoxicity Via Stabilizing Intestinal Permeability and Enhancing Cytoprotection. Current pharmaceutical design 2020.

Gut and liver · 2020 · PMID 31158953 · BioNex Evolve (PubMed-indexed)

This review discusses BPC-157 in stomach and organ protection and the body's response to stress; the abstract does not specify the study populations or experimental models. It reports protective effects on tissues and blood vessel linings, restored blood flow around blockages, and reduced cancer-related muscle wasting. The authors propose BPC-157 as a possible mediator of these protective responses.

Citation: Sikiric P, Hahm KB, Blagaic AB, Tvrdeic A, Pavlov KH, Petrovic A, Kokot A, Gojkovic S, Krezic I, Drmic D, Rucman R, Seiwerth S. Stable Gastric Pentadecapeptide BPC 157, Robert's Stomach Cytoprotection/Adaptive Cytoprotection/Organoprotection, and Selye's Stress Coping Response: Progress, Achievements, and the Future. Gut and liver 2020.

Current pharmaceutical design · 2020 · PMID 32329684 · BioNex Evolve (PubMed-indexed)

This review focused on animal studies of BPC-157 for healing fistulas, abnormal connections involving the digestive tract, in rats. It reported consistent healing of internal and external fistulas and beneficial effects on surgically joined sections of the digestive tract, including under conditions that impair healing.

Citation: Sikiric P, Drmic D, Sever M, Klicek R, Blagaic AB, Tvrdeic A, Kralj T, Kovac KK, Vukojevic J, Siroglavic M, Gojkovic S, Krezic I. Fistulas Healing. Stable Gastric Pentadecapeptide BPC 157 Therapy.. Current pharmaceutical design 2020.

Cell and Tissue Research · 2019 · PMID 30915550 · BioNex Evolve (PubMed-indexed)

This review examined BPC-157 for tendon, ligament, and skeletal muscle healing, drawing mainly on animal studies in small rodents. The reviewed studies consistently reported positive, rapid healing effects across soft tissue injuries. Effectiveness in humans remains unconfirmed, and the evidence comes from a limited set of research groups.

Citation: Gwyer D, Wragg NM, Wilson SL. Gastric pentadecapeptide body protection compound BPC 157 and its role in accelerating musculoskeletal soft tissue healing.. Cell and Tissue Research 2019.

European journal of pharmacology · 2019 · PMID 30690000 · BioNex Evolve (PubMed-indexed)

This animal study examined BPC 157 in rats whose bile ducts had been surgically blocked. BPC 157 reduced jaundice, liver damage, and inflammation, and prevented or rapidly reduced high pressure in the vein carrying blood to the liver. The authors concluded that it may counteract liver scarring and this pressure increase.

Citation: Sever AZ, Sever M, Vidovic T, Lojo N, Kolenc D, Vuletic LB, Drmic D, Kokot A, Zoricic I, Coric M, Vlainic J, Poljak L, Seiwerth S, Sikiric P. Stable gastric pentadecapeptide BPC 157 in the therapy of the rats with bile duct ligation. European journal of pharmacology 2019.

Oxidative medicine and cellular longevity · 2019 · PMID 31976029 · BioNex Evolve (PubMed-indexed)

This animal study tested BPC-157 in rats receiving aspirin, clopidogrel, or cilostazol, which reduce platelet clumping. BPC-157 counteracted their effects in specific platelet-clumping tests, but did not affect the other measured properties of blood clot formation and breakdown.

Citation: Konosic S, Petricevic M, Ivancan V, Konosic L, Goluza E, Krtalic B, Drmic D, Stupnisek M, Seiwerth S, Sikiric P. Intragastric Application of Aspirin, Clopidogrel, Cilostazol, and BPC 157 in Rats: Platelet Aggregation and Blood Clot. Oxidative medicine and cellular longevity 2019.

European journal of pharmacology · 2019 · PMID 31401154 · BioNex Evolve (PubMed-indexed)

This animal study examined BPC-157 and compounds affecting nitric oxide signaling in rats with cyclophosphamide-induced bladder inflammation and bleeding. BPC-157 markedly reduced bladder tissue damage and swelling and returned an abnormal bladder pressure measurement to normal values. These benefits were also observed when BPC-157 was combined with the other compounds.

Citation: Sucic M, Luetic K, Jandric I, Drmic D, Sever AZ, Vuletic LB, Halle ZB, Strinic D, Kokot A, Seiwerth RS, Zoricic I, Blagaic AB, Seiwerth S, Sikiric P. Therapy of the rat hemorrhagic cystitis induced by cyclophosphamide. Stable gastric pentadecapeptide BPC 157, L-arginine, L-NAME. European journal of pharmacology 2019.

Current pharmaceutical design · 2018 · PMID 29879879 · BioNex Evolve (PubMed-indexed)

This review examines BPC-157 in experimental models of digestive tract injury and blood vessel blockage; the abstract does not specify the species used in these models. It reports activation of vessels toward injuries or around blockages, restoring blood flow and largely reversing the course of injury.

Citation: Sikiric P, Rucman R, Turkovic B, Sever M, Klicek R, Radic B, Drmic D, Stupnisek M, Misic M, Vuletic LB, Pavlov KH, Barisic I, Kokot A, Peklic M, Strbe S, Blagaic AB, Tvrdeic A, Rokotov DS, Vrcic H, Staresinic M, Seiwerth S. Novel Cytoprotective Mediator, Stable Gastric Pentadecapeptide BPC 157. Vascular Recruitment and Gastrointestinal Tract Healing. Current pharmaceutical design 2018.

Journal of veterinary pharmacology and therapeutics · 2018 · PMID 29682749 · BioNex Evolve (PubMed-indexed)

This animal field study tested BPC-157 in honeybee colonies infected with the parasite Nosema ceranae. Colonies receiving BPC-157 showed increased colony strength, gradually decreasing parasite spore counts, and markedly less gut damage. The authors reported significant therapeutic effects in these diseased honeybee colonies.

Citation: Tlak Gajger I, Ribarić J, Smodiš Škerl M, Vlainić J, Sikirić P. Stable gastric pentadecapeptide BPC 157 in honeybee (Apis mellifera) therapy, to control Nosema ceranae invasions in apiary conditions. Journal of veterinary pharmacology and therapeutics 2018.

Journal of physiology and pharmacology : an official journal of the Polish Physiological Society · 2018 · PMID 30279308 · BioNex Evolve (PubMed-indexed)

This animal study examined alcohol-induced digestive tract injury in rats, including effects of BPC 157 and nitric oxide signaling. Alcohol contacting the tongue before being swallowed caused less stomach injury than direct stomach administration. The authors reported that BPC 157 apparently healed the alcohol-induced lesions and restored pressure in the muscular valves around the stomach.

Citation: Becejac T, Cesarec V, Drmic D, Hirsl D, Madzarac G, Djakovic Z, Bunjevac I, A Zenko Sever A, Sepac A, Batelja Vuletic L, Stancic Rokotov D, Seiwerth S, Sikiric P. An endogeous defensive concept, renewed cytoprotection/adaptive cytoprotection: intra(per)-oral/intragastric strong alcohol in rat. Involvement of pentadecapeptide BPC 157 and nitric oxide system. Journal of physiology and pharmacology : an official journal of the Polish Physiological Society 2018.

Current pharmaceutical design · 2018 · PMID 29998800 · PubMed

This review compared BPC-157 with other growth factors in experimental models of digestive tract and musculoskeletal healing, including lab studies. The authors reported that BPC-157 was consistently effective across the reviewed digestive tract injury models and improved tendon, ligament, and bone healing. The abstract does not establish effectiveness in humans.

Citation: Seiwerth S, Rucman R, Turkovic B, Sever M, Klicek R, Radic B, Drmic D, Stupnisek M, Misic M, Vuletic LB, Pavlov KH, Barisic I et al.. BPC 157 and Standard Angiogenic Growth Factors. Gastrointestinal Tract Healing, Lessons from Tendon, Ligament, Muscle and Bone Healing.. Current pharmaceutical design 2018.

Current pharmaceutical design · 2017 · PMID 28228068 · BioNex Evolve (PubMed-indexed)

This review explored BPC-157 and the body's response to stress and injury, discussing animal disease models and clinical reports. It described protective and healing effects in the digestive tract and other tissues, alongside effects involving nerve-signaling and nitric oxide pathways. The authors suggested that BPC-157 may help coordinate the body's adaptive response to stress.

Citation: Sikiric P, Seiwerth S, Rucman R, Drmic D, Stupnisek M, Kokot A, Sever M, Zoricic I, Zoricic Z, Batelja L, Ziger T, Luetic K, Vlainic J, Rasic Z, Bencic ML. Stress in Gastrointestinal Tract and Stable Gastric Pentadecapeptide BPC 157. Finally, do we have a Solution?. Current pharmaceutical design 2017.

Journal of physiology and pharmacology : an official journal of the Polish Physiological Society · 2017 · PMID 28614776 · BioNex Evolve (PubMed-indexed)

This animal study examined BPC-157 and drug-induced loss of pressure in the muscular valves at the stomach’s entrance and exit in rats. The tested drugs lowered pressure in both valves, while BPC-157 minimized the initial decline and restored normal pressure and function.

Citation: Vitaic S, Stupnisek M, Drmic D, Bauk L, Kokot A, Klicek R, Vcev A, Luetic K, Seiwerth S, Sikiric P. Nonsteroidal anti-inflammatory drugs-induced failure of lower esophageal and pyloric sphincter and counteraction of sphincters failure with stable gatric pentadecapeptide BPC 157 in rats. Journal of physiology and pharmacology : an official journal of the Polish Physiological Society 2017.

Life sciences · 2016 · PMID 26872976 · BioNex Evolve (PubMed-indexed)

This animal study tested BPC 157 in rats with surgically created abnormal connections between the rectum and vagina. Treated rats showed healing of both openings, no stool passing through the abnormal connection, and reduced internal scarring and intestinal blockage. Untreated rats showed persistent defects and poor healing.

Citation: Baric M, Sever AZ, Vuletic LB, Rasic Z, Sever M, Drmic D, Pavelic-Turudic T, Sucic M, Vrcic H, Seiwerth S, Sikiric P. Stable gastric pentadecapeptide BPC 157 heals rectovaginal fistula in rats. Life sciences 2016.

Current neuropharmacology · 2016 · PMID 27138887 · BioNex Evolve (PubMed-indexed)

This review explores BPC-157 and brain–gut interactions, including animal research on nerve injury, brain injury, and spinal cord compression in rats. It reports protective effects on nerves and improvements in injury-related problems, suggesting BPC-157 may have potential in central nervous system disorders. The abstract mentions human trials but provides no detailed trial results.

Citation: Sikiric P, Seiwerth S, Rucman R, Kolenc D, Vuletic LB, Drmic D, Grgic T, Strbe S, Zukanovic G, Crvenkovic D, Madzarac G, Rukavina I, Sucic M, Baric M, Starcevic N, Krstonijevic Z, Bencic ML, Filipcic I, Rokotov DS, Vlainic J. Brain-gut Axis and Pentadecapeptide BPC 157: Theoretical and Practical Implications. Current neuropharmacology 2016.

European journal of pharmacology · 2016 · PMID 26698393 · BioNex Evolve (PubMed-indexed)

This animal study examined BPC-157 and nitric oxide signaling in pupil responses in rats and guinea pigs. BPC-157 did not change normal pupils but counteracted atropine-induced pupil widening and modified pupil narrowing caused by other compounds. The authors suggested that its effects may involve nitric oxide and nerve-signaling mechanisms.

Citation: Kokot A, Zlatar M, Stupnisek M, Drmic D, Radic R, Vcev A, Seiwerth S, Sikiric P. NO system dependence of atropine-induced mydriasis and L-NAME- and L-arginine-induced miosis: Reversal by the pentadecapeptide BPC 157 in rats and guinea pigs. European journal of pharmacology 2016.

PloS one · 2016 · PMID 27627764 · BioNex Evolve (PubMed-indexed)

This animal study examined BPC-157 and other compounds in rats after extensive small-intestine removal, including groups exposed to diclofenac and a nitric oxide blocker. BPC-157 completely alleviated the reported problems across the tested surgical groups, including impaired intestinal healing and organ damage. L-arginine alleviated only the additional worsening caused by the nitric oxide blocker.

Citation: Lojo N, Rasic Z, Zenko Sever A, Kolenc D, Vukusic D, Drmic D, Zoricic I, Sever M, Seiwerth S, Sikiric P. Effects of Diclofenac, L-NAME, L-Arginine, and Pentadecapeptide BPC 157 on Gastrointestinal, Liver, and Brain Lesions, Failed Anastomosis, and Intestinal Adaptation Deterioration in 24 Hour-Short-Bowel Rats. PloS one 2016.

European journal of pharmacology · 2016 · PMID 26875638 · PubMed

This animal study tested BPC-157 in male rats with surgically created abnormal connections between the colon and bladder. Compared with controls showing poor healing, BPC-157 improved and eventually healed both defects. Treated rats also showed no stool passing into urine or through the abnormal connection.

Citation: Grgic T, Grgic D, Drmic D, Sever AZ, Petrovic I, Sucic M, Kokot A, Klicek R, Sever M, Seiwerth S, Sikiric P. Stable gastric pentadecapeptide BPC 157 heals rat colovesical fistula.. European journal of pharmacology 2016.

Experimental eye research · 2015 · PMID 25912999 · BioNex Evolve (PubMed-indexed)

This animal study tested BPC-157 eye drops after penetrating corneal injuries in rats. BPC-157 accelerated wound closure and restoration of corneal transparency compared with controls. Treated eyes generally had no new blood vessels, and vessels that did form did not reach the injury.

Citation: Masnec S, Kokot A, Zlatar M, Kalauz M, Kunjko K, Radic B, Klicek R, Drmic D, Lazic R, Brcic L, Radic R, Ivekovic R, Seiwerth S, Sikiric P. Perforating corneal injury in rat and pentadecapeptide BPC 157. Experimental eye research 2015.

Journal of physiology and pharmacology : an official journal of the Polish Physiological Society · 2015 · PMID 26348082 · BioNex Evolve (PubMed-indexed)

This animal study tested BPC-157 and substances affecting nitric oxide signaling in rats with an abnormal passage between the small intestine and skin. BPC-157 counteracted persistent wounds, leakage, digestive valve failure, and deaths, including worsening caused by nitric oxide inhibition. The authors suggest nitric oxide signaling is involved in this healing response.

Citation: Skorjanec S, Kokot A, Drmic D, Radic B, Sever M, Klicek R, Kolenc D, Zenko A, Lovric Bencic M, Belosic Halle Z, Situm A, Zivanovic Posilovic G, Masnec S, Suran J, Aralica G, Seiwerth S, Sikiric P. Duodenocutaneous fistula in rats as a model for "wound healing-therapy" in ulcer healing: the effect of pentadecapeptide BPC 157, L-nitro-arginine methyl ester and L-arginine. Journal of physiology and pharmacology : an official journal of the Polish Physiological Society 2015.

ClinicalTrials.gov · 2015 · NCT02637284 · ClinicalTrials.gov

This early-phase human trial record describes a planned study of PCO-02, containing BPC-157, in healthy volunteers to assess safety and how the peptide moves through the body. Its status is listed as unknown, and no results are provided.

Population / model

Healthy Volunteers

Citation: PharmaCotherapia d.o.o.. Phase I, Pilot Study in Healthy Volunteers, to Assess the Safety and Pharmacokinetics of PCO-02, Which Active Ingredient is BPC-157, a Penta-deca-peptide From Gastric Source. ClinicalTrials.gov 2015.

Current pharmaceutical design · 2014 · PMID 23755725 · BioNex Evolve (PubMed-indexed)

This review examines BPC-157 and nitric oxide signaling in experimental injury and healing models; the abstract does not specify the species studied. It describes improved healing and effects on blood vessel integrity, clotting, and bleeding. Whether these effects translate into improved clinical outcomes remains to be determined.

Citation: Sikiric P, Seiwerth S, Rucman R, Turkovic B, Rokotov DS, Brcic L, Sever M, Klicek R, Radic B, Drmic D, Ilic S, Kolenc D, Aralica G, Stupnisek M, Suran J, Barisic I, Dzidic S, Vrcic H, Sebecic B. Stable gastric pentadecapeptide BPC 157-NO-system relation. Current pharmaceutical design 2014.

Current pharmaceutical design · 2014 · PMID 23782145 · PubMed

This review examined BPC-157's reported effects on blood vessels after injury, including clotting, swelling, and new vessel formation; the abstract does not specify the species studied. The authors concluded that BPC-157 strongly regulates blood vessel responses through several signaling pathways, helping optimize healing. These are review conclusions, not results from a new human trial.

Citation: Seiwerth S, Brcic L, Vuletic LB, Kolenc D, Aralica G, Misic M, Zenko A, Drmic D, Rucman R, Sikiric P. BPC 157 and blood vessels.. Current pharmaceutical design 2014.

European journal of pharmacology · 2014 · PMID 24486708 · PubMed

This animal study tested BPC-157 in rats and mice with severe allergy-like reactions triggered by dextran or egg white. The authors reported that BPC-157 may prevent these reactions and rescue already advanced reactions after exposure. The comparison drugs chloropyramine and cimetidine were only moderately effective when used alone.

Citation: Duplancic B, Stambolija V, Holjevac J, Zemba M, Balenovic I, Drmic D, Suran J, Radic B, Filipovic M, Blagaic AB, Brcic L, Kolenc D et al.. Pentadecapeptide BPC 157 and anaphylactoid reaction in rats and mice after intravenous dextran and white egg administration.. European journal of pharmacology 2014.

Molecules (Basel, Switzerland) · 2014 · PMID 25415472 · PubMed

This lab study tested BPC-157 in tendon repair cells isolated from male rats. BPC-157 increased growth hormone receptor expression, and adding growth hormone increased cell multiplication and activated a related signaling pathway. The authors suggest this receptor increase may strengthen growth hormone's effects on cell growth and contribute to tendon healing.

Citation: Chang CH, Tsai WC, Hsu YH, Pang JH. Pentadecapeptide BPC 157 enhances the growth hormone receptor expression in tendon fibroblasts.. Molecules (Basel, Switzerland) 2014.

Medical science monitor basic research · 2013 · PMID 23478678 · BioNex Evolve (PubMed-indexed)

This animal study tested BPC-157 in female rats with injury-induced stress urinary incontinence. BPC-157 improved the pressure needed to trigger urine leakage and preserved urethral muscle structure, with some treated groups reaching values seen in healthy rats. It did not change leakage pressure in healthy rats.

Citation: Jandric I, Vrcic H, Jandric Balen M, Kolenc D, Brcic L, Radic B, Drmic D, Seiwerth S, Sikiric P. Salutary effect of gastric pentadecapeptide BPC 157 in two different stress urinary incontinence models in female rats. Medical science monitor basic research 2013.

European journal of pharmacology · 2013 · PMID 23220707 · BioNex Evolve (PubMed-indexed)

This animal study tested BPC 157 in rats with abnormal connections between the esophagus and skin, while examining nitric oxide signaling. BPC 157 accelerated healing, reduced leakage, and restored pressure in the muscular valves around the stomach, with almost no esophageal inflammation. No deaths occurred in BPC 157-treated rats during the study.

Citation: Cesarec V, Becejac T, Misic M, Djakovic Z, Olujic D, Drmic D, Brcic L, Rokotov DS, Seiwerth S, Sikiric P. Pentadecapeptide BPC 157 and the esophagocutaneous fistula healing therapy. European journal of pharmacology 2013.

Current pharmaceutical design · 2013 · PMID 22950504 · BioNex Evolve (PubMed-indexed)

This review discusses BPC-157 and NSAID-related damage to the digestive tract, liver, and brain, alongside bleeding and platelet changes; the abstract does not identify the species underlying these findings. It reports protective effects and proposes BPC-157 as a possible NSAID antidote, rather than presenting a new human efficacy trial.

Citation: Sikiric P, Seiwerth S, Rucman R, Turkovic B, Rokotov DS, Brcic L, Sever M, Klicek R, Radic B, Drmic D, Ilic S, Kolenc D, Aralica G, Safic H, Suran J, Rak D, Dzidic S, Vrcic H, Sebecic B. Toxicity by NSAIDs. Counteraction by stable gastric pentadecapeptide BPC 157. Current pharmaceutical design 2013.

Journal of physiology and pharmacology : an official journal of the Polish Physiological Society · 2013 · PMID 24304574 · BioNex Evolve (PubMed-indexed)

This animal study tested BPC-157 in rat models of chemically induced colon inflammation, surgically rejoined colon tissue, and toxin-induced brain injury. BPC-157 improved healing of the inflamed and surgically joined colon. In the brain-injury model, it reduced nerve damage and counteracted coordination problems and impaired forelimb function.

Citation: Klicek R, Kolenc D, Suran J, Drmic D, Brcic L, Aralica G, Sever M, Holjevac J, Radic B, Turudic T, Kokot A, Patrlj L, Rucman R, Seiwerth S, Sikiric P. Stable gastric pentadecapeptide BPC 157 heals cysteamine-colitis and colon-colon-anastomosis and counteracts cuprizone brain injuries and motor disability. Journal of physiology and pharmacology : an official journal of the Polish Physiological Society 2013.

Current medicinal chemistry · 2012 · PMID 22300085 · BioNex Evolve (PubMed-indexed)

This review discussed BPC 157 for ulcerative colitis, drawing on animal research and noting human testing limited to phase II trials. It highlighted animal findings involving intestinal wound healing, short bowel syndrome, and abnormal intestinal connections, alongside reported benefits in human inflammatory bowel disease trials. The authors suggested potential for further research in inflammatory bowel disease.

Citation: Sikiric P, Seiwerth S, Rucman R, Turkovic B, Rokotov DS, Brcic L, Sever M, Klicek R, Radic B, Drmic D, Ilic S, Kolenc D, Stambolija V, Zoricic Z, Vrcic H, Sebecic B. Focus on ulcerative colitis: stable gastric pentadecapeptide BPC 157. Current medicinal chemistry 2012.

Journal of applied physiology (Bethesda, Md. : 1985) · 2011 · PMID 21030672 · BioNex Evolve (PubMed-indexed)

This laboratory study examined BPC-157 in cultured rat Achilles tendon tissue and tendon cells. BPC-157 increased tissue outgrowth, cell movement, and cell survival under oxidative stress, but did not directly increase cell multiplication. The authors suggest activation of the FAK–paxillin signaling pathway likely contributes to these effects.

Citation: Chang CH, Tsai WC, Lin MS, Hsu YH, Pang JH. The promoting effect of pentadecapeptide BPC 157 on tendon healing involves tendon outgrowth, cell survival, and cell migration.. Journal of applied physiology (Bethesda, Md. : 1985) 2011.

European journal of pharmacology · 2011 · PMID 21645505 · BioNex Evolve (PubMed-indexed)

This animal study examined BPC-157 in rats with damage caused by repeated ibuprofen exposure. BPC-157 counteracted the reported adverse effects, including brain dysfunction linked to liver damage, stomach lesions, liver enlargement, and elevated liver blood-test markers. Treated rats showed no behavioral disturbances and maintained normal weight gain.

Citation: Ilic S, Drmic D, Zarkovic K, Kolenc D, Brcic L, Radic B, Djuzel V, Blagaic AB, Romic Z, Dzidic S, Kalogjera L, Seiwerth S, Sikiric P. Ibuprofen hepatic encephalopathy, hepatomegaly, gastric lesion and gastric pentadecapeptide BPC 157 in rats. European journal of pharmacology 2011.

Current pharmaceutical design · 2011 · PMID 21548867 · BioNex Evolve (PubMed-indexed)

This review discusses BPC-157 for digestive tract injuries, describing animal studies in rats and mentioning human inflammatory bowel disease trials. Rat findings included reduced esophageal inflammation, restored sphincter function, and healing of intestinal surgical connections and abnormal openings. The authors suggest BPC-157 may improve gastrointestinal care, but the abstract provides no human efficacy results.

Citation: Sikiric P, Seiwerth S, Rucman R, Turkovic B, Rokotov DS, Brcic L, Sever M, Klicek R, Radic B, Drmic D, Ilic S, Kolenc D, Vrcic H, Sebecic B. Stable gastric pentadecapeptide BPC 157: novel therapy in gastrointestinal tract. Current pharmaceutical design 2011.

Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2010 · PMID 20225319 · BioNex Evolve (PubMed-indexed)

This animal study examined BPC-157 after surgical cutting of a knee ligament in rats. Treated rats showed consistent improvements in ligament function, mechanical strength, visible healing, and microscopic tissue repair.

Citation: Cerovecki T, Bojanic I, Brcic L, Radic B, Vukoja I, Seiwerth S, Sikiric P. Pentadecapeptide BPC 157 (PL 14736) improves ligament healing in the rat. Journal of orthopaedic research : official publication of the Orthopaedic Research Society 2010.

Regulatory peptides · 2010 · PMID 19903499 · BioNex Evolve (PubMed-indexed)

This animal study tested BPC-157 in rats with severed sciatic nerves. BPC-157 markedly improved nerve healing, with faster nerve-fiber regeneration, improved electrical responses, and better walking function.

Citation: Gjurasin M, Miklic P, Zupancic B, Perovic D, Zarkovic K, Brcic L, Kolenc D, Radic B, Seiwerth S, Sikiric P. Peptide therapy with pentadecapeptide BPC 157 in traumatic nerve injury. Regulatory peptides 2010.

Regulatory peptides · 2010 · PMID 19931318 · BioNex Evolve (PubMed-indexed)

This animal study examined BPC-157 given before experimentally induced traumatic brain injury in mice. It reduced brain damage, bleeding, swelling, unconsciousness, and mortality during early follow-up. Benefits depended on injury severity and the timing and regimen of administration.

Citation: Tudor M, Jandric I, Marovic A, Gjurasin M, Perovic D, Radic B, Blagaic AB, Kolenc D, Brcic L, Zarkovic K, Seiwerth S, Sikiric P. Traumatic brain injury in mice and pentadecapeptide BPC 157 effect. Regulatory peptides 2010.

Digestive diseases and sciences · 2009 · PMID 19093208 · BioNex Evolve (PubMed-indexed)

This animal study examined BPC 157 in rats with short bowel syndrome after extensive small intestine removal. Treated rats gained weight rather than showing progressive weight loss, developed larger intestinal absorption structures, and had stronger surgical joins. The authors suggested that BPC 157 could be helpful for short bowel syndrome.

Citation: Sever M, Klicek R, Radic B, Brcic L, Zoricic I, Drmic D, Ivica M, Barisic I, Ilic S, Berkopic L, Blagaic AB, Coric M, Kolenc D, Vrcic H, Anic T, Seiwerth S, Sikiric P. Gastric pentadecapeptide BPC 157 and short bowel syndrome in rats. Digestive diseases and sciences 2009.

Journal of physiology and pharmacology : an official journal of the Polish Physiological Society · 2009 · PMID 20388960 · BioNex Evolve (PubMed-indexed)

This animal study tested BPC 157 in rats after the abdominal aorta was surgically cut and rejoined. Immediate use reduced clot formation and preserved walking ability and muscle strength. When given after impairment had developed, BPC 157 rapidly restored hind-limb function and strength, and no clot was visible at the surgical join.

Citation: Hrelec M, Klicek R, Brcic L, Brcic I, Cvjetko I, Seiwerth S, Sikiric P. Abdominal aorta anastomosis in rats and stable gastric pentadecapeptide BPC 157, prophylaxis and therapy. Journal of physiology and pharmacology : an official journal of the Polish Physiological Society 2009.

Regulatory peptides · 2009 · PMID 19465062 · BioNex Evolve (PubMed-indexed)

This animal study tested BPC-157 in rats with methyldigoxin-induced heart rhythm disturbances. BPC-157 prevented or reduced abnormal rhythms and heart conduction blocks; deaths were prevented, reduced, or delayed depending on the regimen. The authors concluded that these effects occurred mainly through interaction with the nitric oxide signaling system.

Citation: Balenovic D, Bencic ML, Udovicic M, Simonji K, Hanzevacki JS, Barisic I, Kranjcevic S, Prkacin I, Coric V, Brcic L, Coric M, Brcic I, Borovic S, Radic B, Drmic D, Vrcic H, Seiwerth S, Sikiric P. Inhibition of methyldigoxin-induced arrhythmias by pentadecapeptide BPC 157: a relation with NO-system. Regulatory peptides 2009.

Journal of physiology and pharmacology : an official journal of the Polish Physiological Society · 2009 · PMID 20388964 · BioNex Evolve (PubMed-indexed)

This laboratory and animal study examined BPC-157 and blood-vessel formation during muscle and tendon healing. BPC-157 had no direct effect on blood-vessel formation in cell cultures, but treated animals showed better-regulated vessel formation and healing. The findings suggest this effect is linked to increased activity of VEGF, a signal that promotes blood-vessel growth.

Citation: Brcic L, Brcic I, Staresinic M, Novinscak T, Sikiric P, Seiwerth S. Modulatory effect of gastric pentadecapeptide BPC 157 on angiogenesis in muscle and tendon healing. Journal of physiology and pharmacology : an official journal of the Polish Physiological Society 2009.

Journal of physiology and pharmacology : an official journal of the Polish Physiological Society · 2009 · PMID 20388962 · BioNex Evolve (PubMed-indexed)

This animal study examined whether BPC-157 changes morphine’s pain-relieving effects in mice using a hot-plate test. BPC-157 counteracted morphine’s pain relief and the additional enhancement caused by haloperidol, but did not relieve pain on its own. The authors interpreted the findings as indicating involvement of brain dopamine signaling.

Citation: Boban Blagaic A, Turcic P, Blagaic V, Dubovecak M, Jelovac N, Zemba M, Radic B, Becejac T, Stancic Rokotov D, Sikiric P. Gastric pentadecapeptide BPC 157 counteracts morphine-induced analgesia in mice. Journal of physiology and pharmacology : an official journal of the Polish Physiological Society 2009.

Journal of pharmacological sciences · 2008 · PMID 18818478 · PubMed

This animal study examined BPC-157 and nitric oxide signaling in rats with abnormal connections between the colon and skin. BPC-157 accelerated healing of both wounds and promoted closure, improving tissue strength and resistance to leakage. Its benefits remained when nitric oxide production was inhibited or its building material was supplied.

Citation: Klicek R, Sever M, Radic B, Drmic D, Kocman I, Zoricic I, Vuksic T, Ivica M, Barisic I, Ilic S, Berkopic L, Vrcic H et al.. Pentadecapeptide BPC 157, in clinical trials as a therapy for inflammatory bowel disease (PL14736), is effective in the healing of colocutaneous fistulas in rats: role of the nitric oxide-system.. Journal of pharmacological sciences 2008.

European journal of pharmacology · 2005 · PMID 15840402 · BioNex Evolve (PubMed-indexed)

This animal study tested BPC-157 in rats with drug-induced serotonin syndrome. BPC-157 reduced severe syndrome signs, particularly overheating and shaking, and did not itself trigger the syndrome in the tested conditions. The authors suggested that its effects were mainly related to counteracting responses involving serotonin 5-HT2A receptors.

Citation: Boban Blagaic A, Blagaic V, Mirt M, Jelovac N, Dodig G, Rucman R, Petek M, Turkovic B, Anic T, Dubovecak M, Staresinic M, Seiwerth S, Sikiric P. Gastric pentadecapeptide BPC 157 effective against serotonin syndrome in rats. European journal of pharmacology 2005.

Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2003 · PMID 14554208 · PubMed

This animal and lab study tested BPC-157 in rats with severed Achilles tendons and in cultured tendon cells. Rats showed improved tendon strength, function, and tissue repair, with restoration of tendon integrity. In cultured cells, BPC-157 counteracted growth inhibition caused by a damaging compound but did not stimulate growth on its own.

Citation: Staresinic M, Sebecic B, Patrlj L, Jadrijevic S, Suknaic S, Perovic D, Aralica G, Zarkovic N, Borovic S, Srdjak M, Hajdarevic K, Kopljar M et al.. Gastric pentadecapeptide BPC 157 accelerates healing of transected rat Achilles tendon and in vitro stimulates tendocytes growth.. Journal of orthopaedic research : official publication of the Orthopaedic Research Society 2003.

Journal of physiology, Paris · 1997 · PMID 9403790 · PubMed

This animal study tested BPC-157 in rats with skin wounds, surgically joined colon segments, and implanted sponges used to study new blood vessel formation. Researchers assessed repair tissue, collagen, blood vessels, and tissue strength. Significant differences from untreated controls across the experiments supported a healing-promoting effect.

Citation: Seiwerth S, Sikiric P, Grabarevic Z, Zoricic I, Hanzevacki M, Ljubanovic D, Coric V, Konjevoda P, Petek M, Rucman R, Turkovic B, Perovic D et al.. BPC 157's effect on healing.. Journal of physiology, Paris 1997.

The Journal of sports medicine and physical fitness · 2026 · PMID 41880199 · PubMed

This review examined peptide and peptide-like drug use among recreational and professional athletes and bodybuilders. Clinical evidence supporting these uses is limited, and emerging data highlight potential cardiovascular, metabolic, and psychiatric risks. The review also identified mislabeled or contaminated products, unknown use rates, and poorly defined long-term risks as major concerns.

Citation: Coutinho LFD, DE Oliveira Neves LF, Camilo RP. A new era of doping? Use of peptide and peptide-analog drugs in recreational and professional sport and bodybuilding: a critical review.. The Journal of sports medicine and physical fitness 2026.

JBJS reviews · 2026 · PMID 42160466 · PubMed

This review examines human studies and research relevant to clinical use of injectable peptides in sports medicine. Reproducible randomized evidence of improved knee osteoarthritis symptoms was limited to GLP-1 receptor agonists, mainly through weight loss. CJC-1295, ipamorelin, and other experimental peptides had uncertain safety, product quality concerns, and widespread antidoping restrictions.

Citation: Villegas Meza AD, Nocek M, Mitchell BC, Lizarraga M, DeFoor MT, Ruzbarsky JJ, Huard J, Philippon MJ. Injectable Peptides in Sports Medicine: A Structured Narrative Review of Evidence, Safety, and Antidoping Implications.. JBJS reviews 2026.

Frontiers in endocrinology · 2026 · PMID 42395176 · PubMed

This review compared clinical evidence with online self-use practices for peptides affecting growth-hormone pathways, including CJC-1295 and ipamorelin. Human evidence ranged from randomized trials to no human studies, leaving performance and body-composition benefits uncertain. Reported adverse effects included hormonal and blood-sugar disturbances, fluid retention, muscle or joint pain, and injection-site reactions.

Citation: Dominikowski A, Rękoś Z, Olejarz M, Szczepanek-Parulska E, Domin R, RuchaŁa M. The emerging landscape of performance-enhancing peptides modulating GH-IGF1 axis: bridging the gap between clinical evidence and patient self-administration.. Frontiers in endocrinology 2026.

Translational andrology and urology · 2020 · PMID 32257855 · PubMed

This review examined growth hormone-stimulating compounds, including ipamorelin and sermorelin, for body composition and symptoms in men with low testosterone or related metabolic problems. The authors describe potential improvements in body composition through growth hormone and IGF-I stimulation. However, they emphasize that clinical evidence in men with low testosterone remains limited.

Citation: Sinha DK, Balasubramanian A, Tatem AJ, Rivera-Mirabal J, Yu J, Kovac J, Pastuszak AW, Lipshultz LI. Beyond the androgen receptor: the role of growth hormone secretagogues in the modern management of body composition in hypogonadal males.. Translational andrology and urology 2020.

Methods (San Diego, Calif.) · 2012 · PMID 21871962 · PubMed

This laboratory methods report describes purifying prohibited peptide hormones, including CJC-1295, from blood or urine samples before mass spectrometry testing for doping control. The method enabled sensitive detection of urinary peptides at physiologically relevant levels, with antibody-based purification supporting reliable analysis.

Citation: Thomas A, Schänzer W, Delahaut P, Thevis M. Immunoaffinity purification of peptide hormones prior to liquid chromatography-mass spectrometry in doping controls.. Methods (San Diego, Calif.) 2012.

Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society · 2009 · PMID 19231263 · PubMed

This animal study compared growth hormone and ipamorelin in rats experiencing steroid-induced tissue breakdown. Both counteracted nitrogen loss and reduced the liver’s conversion of nitrogen into urea, although ipamorelin was less effective under the tested conditions.

Citation: Aagaard NK, Grøfte T, Greisen J, Malmlöf K, Johansen PB, Grønbaek H, Ørskov H, Tygstrup N, Vilstrup H. Growth hormone and growth hormone secretagogue effects on nitrogen balance and urea synthesis in steroid treated rats.. Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society 2009.

Endocrine · 2001 · PMID 11322495 · PubMed

This animal study examined growth hormone-releasing compounds in rats and whether the digestive tract contributes to their effects. The compounds accumulated in the stomach, and removing the digestive tract significantly reduced the growth hormone response to GHRP-6. The findings suggest that ghrelin may mediate part of the growth hormone-releasing effect of these compounds.

Citation: Ahnfelt-Rønne I, Nowak J, Olsen UB. Do growth hormone-releasing peptides act as ghrelin secretagogues?. Endocrine 2001.

Biochemical and biophysical research communications · 2001 · PMID 11162489 · PubMed

This animal study compared growth hormone with growth hormone-releasing compounds, including ipamorelin, in mice with deficient or normal growth hormone function. The releasing compounds increased body fat, and increased food intake and leptin in mice with normal growth hormone function. The findings indicate that these compounds increase body fat through mechanisms independent of growth hormone that may include increased feeding.

Citation: Lall S, Tung LY, Ohlsson C, Jansson JO, Dickson SL. Growth hormone (GH)-independent stimulation of adiposity by GH secretagogues.. Biochemical and biophysical research communications 2001.

Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society · 1999 · PMID 10629165 · PubMed

This animal study examined ipamorelin in rats receiving the steroid methylprednisolone. The steroid did not reduce the immediate growth-hormone response to ipamorelin. Repeated ipamorelin administration increased IGF-I, a growth-related hormone, and reduced body-weight loss during recovery from surgery.

Citation: Malmlöf K, Johansen PB, Haahr PM, Wilken M, Oxlund H. Methylprednisolone does not inhibit the release of growth hormone after intravenous injection of a novel growth hormone secretagogue in rats.. Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society 1999.

Journal of medicinal chemistry · 1998 · PMID 9733496 · PubMed

This animal and lab study tested compounds developed from ipamorelin using a rat pituitary assay, pigs, and dogs. Researchers made smaller compounds that retained growth hormone-releasing activity in pigs, and most tested compounds showed absorption when given orally to dogs.

Citation: Hansen TK, Ankersen M, Hansen BS, Raun K, Nielsen KK, Lau J, Peschke B, Lundt BF, Thøgersen H, Johansen NL, Madsen K, Andersen PH. Novel orally active growth hormone secretagogues.. Journal of medicinal chemistry 1998.

Molecules (Basel, Switzerland) · 2021 · PMID 34500605 · PubMed

This animal study tested nasal DSIP given before and after an experimentally induced stroke in rats. DSIP significantly accelerated recovery of motor performance on a rotating-rod test. The area of damaged brain tissue was smaller in DSIP-treated animals, but that difference was not statistically significant.

Citation: Tukhovskaya EA, Ismailova AM, Shaykhutdinova ER, Slashcheva GA, Prudchenko IA, Mikhaleva II, Khokhlova ON, Murashev AN, Ivanov VT. Delta Sleep-Inducing Peptide Recovers Motor Function in SD Rats after Focal Stroke.. Molecules (Basel, Switzerland) 2021.

Journal of neurochemistry · 2006 · PMID 16539679 · PubMed

This review examined animal and laboratory research on DSIP and its proposed role in sleep. It concluded that evidence for DSIP as a natural sleep-promoting factor remains weak and that its natural occurrence and biological activity remain unclear. The authors proposed that related, still-unidentified peptides might explain some reported effects.

Citation: Kovalzon VM, Strekalova TV. Delta sleep-inducing peptide (DSIP): a still unresolved riddle.. Journal of neurochemistry 2006.

Seizure · 2005 · PMID 15911358 · PubMed

This animal study tested DSIP and its analogue DSIP-12 in rats with chemically induced, sound-triggered seizures. Both peptides significantly reduced seizure occurrence, severity, and duration while increasing delta and theta brain-wave activity. DSIP-12 was more effective than DSIP, suggesting potential antiseizure activity in this animal model.

Citation: Stanojlović OP, Zivanović DP, Mirković SD, Mikhaleva II. Antiepileptic activity of delta sleep-inducing peptide and its analogue in metaphit-provoked seizures in rats.. Seizure 2005.

Annals of the New York Academy of Sciences · 1995 · PMID 8597403 · PubMed

This animal study examined DSIP’s delayed effects on stress-related peptides and hormones in rat strains with different resistance to emotional stress. DSIP caused marked changes in substance P, beta-endorphin, and corticosterone, suggesting these changes may contribute to its longer-term stress-coping effects. Stimulation of resistance mechanisms was less pronounced in August rats than in Wistar rats.

Citation: Sudakov KV, Coghlan JP, Kotov AV, Salieva RM, Polyntsev YuV, Koplik EV. Delta-sleep-inducing peptide sequels in the mechanisms of resistance to emotional stress.. Annals of the New York Academy of Sciences 1995.

Neuropsychobiology · 1992 · PMID 1299794 · PubMed

This double-blind human study compared DSIP with placebo in people with chronic insomnia. Objective sleep efficiency and time to fall asleep improved, but the effects were weak and partly may have reflected changes in the placebo group; perceived sleep quality did not improve. The authors concluded that short-term DSIP was unlikely to provide major therapeutic benefit.

Citation: Bes F, Hofman W, Schuur J, Van Boxtel C. Effects of delta sleep-inducing peptide on sleep of chronic insomniac patients. A double-blind study.. Neuropsychobiology 1992.

Peptides · 1992 · PMID 1437707 · PubMed

This animal study mapped DSIP-like material in the brain and pituitary gland of a cartilaginous fish. It provided the first evidence of a DSIP-related peptide in fish, with a distribution suggesting possible roles in nerve signaling and regulation of pituitary activity.

Citation: Vallarino M, Feuilloley M, Yon L, Charnay Y, Vaudry H. Immunohistochemical localization of delta sleep-inducing peptide (DSIP) in the brain and pituitary of the cartilaginous fish Scyliorhinus canicula.. Peptides 1992.

Brain research · 1990 · PMID 2322843 · PubMed

This animal study tested how DSIP and its modified form, P-DSIP, affected apomorphine-induced lowering of body temperature in rats. Both enhanced the temperature drop, but P-DSIP acted and wore off more quickly. The findings suggest a connection with dopamine-related temperature regulation.

Citation: Tsunashima K, Masui A, Kato N. The effect of delta sleep-inducing peptide (DSIP) and phosphorylated DSIP (P-DSIP) on the apomorphine-induced hypothermia in rats.. Brain research 1990.

Life sciences · 1987 · PMID 3550343 · PubMed

This animal and laboratory study tested DSIP’s effects on luteinizing hormone (LH) release in rats whose ovaries had been removed. DSIP stimulated LH release after estrogen and progesterone priming, but not without it, and had no direct effect on isolated pituitary tissue. The findings support the hypothesis that DSIP may act through brain circuits controlling LH release.

Citation: Sahu A, Kalra SP. Delta sleep-inducing peptide (DSIP) stimulates LH release in steroid-primed ovariectomized rats.. Life sciences 1987.

Brain research bulletin · 1987 · PMID 3121137 · PubMed

This animal and laboratory study examined DSIP’s effects on reproductive hormone release in rats and isolated rat tissues. Brain-administered DSIP increased luteinizing hormone (LH), but not follicle-stimulating hormone (FSH), in rats whose ovaries had been removed. It stimulated LH-releasing hormone from hypothalamic tissue but had no effect on cultured pituitary cells, supporting a site of action in the hypothalamus.

Citation: Iyer KS, McCann SM. Delta sleep inducing peptide (DSIP) stimulates the release of LH but not FSH via a hypothalamic site of action in the rat.. Brain research bulletin 1987.

European neurology · 1987 · PMID 3622582 · PubMed

This placebo-controlled, double-blind human trial studied DSIP in middle-aged people with chronic insomnia. Nighttime sleep improved, and daytime alertness and performance increased significantly. Sleep improvements persisted during the first night after treatment ended.

Citation: Schneider-Helmert D. Effects of delta-sleep-inducing peptide on 24-hour sleep-wake behaviour in severe chronic insomnia.. European neurology 1987.

Peptides · 1986 · PMID 3550726 · PubMed

This review summarized DSIP research, including sleep effects in animals and investigations of its potential use for insomnia, pain, and withdrawal. It described additional reports of sleep-promoting or sleep-supporting effects in animals. DSIP's physiological roles and a proposed mechanism involving adrenaline-related nerve signaling remained unestablished.

Citation: Graf MV, Kastin AJ. Delta-sleep-inducing peptide (DSIP): an update.. Peptides 1986.

Neuroscience letters · 1985 · PMID 3840239 · PubMed

This animal study compared sleep and wakefulness in cats after DSIP or saline injections. DSIP reduced sleep, specifically light slow-wave sleep and REM sleep, and delayed the onset of REM sleep. The findings suggested increased wakefulness at the expense of light slow-wave sleep, alongside a specific REM-reducing effect.

Citation: Sommerfelt L. Reduced sleep in cats after intraperitoneal injection of delta-sleep-inducing peptide (DSIP).. Neuroscience letters 1985.

Neuroscience and biobehavioral reviews · 1984 · PMID 6145137 · PubMed

This review summarized DSIP research in humans and animals. It reported that DSIP mainly induced deep, slow-wave sleep in rabbits, rats, mice, and humans, while effects on REM sleep were more pronounced in cats. It also described effects beyond sleep, including changes in brain signaling, hormone levels, and daily activity patterns.

Citation: Graf MV, Kastin AJ. Delta-sleep-inducing peptide (DSIP): a review.. Neuroscience and biobehavioral reviews 1984.

European neurology · 1984 · PMID 6548966 · PubMed

This report summarized animal and laboratory research on DSIP, alongside observations in human biological samples. DSIP produced sleep effects that varied by species and also affected daily activity rhythms, brain chemicals, and hormone levels. The report described blood-brain barrier passage and DSIP-like material in animal and human samples, with findings suggesting functions beyond sleep.

Citation: Schoenenberger GA. Characterization, properties and multivariate functions of delta-sleep-inducing peptide (DSIP).. European neurology 1984.

Life sciences · 1983 · PMID 6688848 · PubMed

This animal study examined whether a DSIP-related peptide could enter the bloodstream through the digestive tract of unweaned rat pups. The results showed that the orally administered peptide could be absorbed into circulation. Findings with a radioactively labeled peptide also suggested that it crossed the blood-brain barrier.

Citation: Banks WA, Kastin AJ, Coy DH. Delta sleep-inducing peptide (DSIP)-like material is absorbed by the gastrointestinal tract of the neonatal rat.. Life sciences 1983.

Pharmacology, biochemistry, and behavior · 1982 · PMID 6897451 · PubMed

This animal study examined whether injected DSIP and related peptides entered the fluid surrounding the brain and spinal cord in anesthetized dogs. The findings supported passage across the blood-brain barrier, probably by DSIP not bound to a carrier protein. A specific, capacity-limited transport process was possible, but nonspecific passage could not be ruled out.

Citation: Banks WA, Kastin AJ, Coy DH. Delta sleep-inducing peptide crosses the blood-brain-barrier in dogs: some correlations with protein binding.. Pharmacology, biochemistry, and behavior 1982.

Experientia · 1981 · PMID 7028502 · PubMed

This human trial tested synthetic DSIP in middle-aged people with chronic insomnia. It reported longer, better-quality sleep with fewer interruptions and slightly more REM sleep, without daytime sedation or other reported side effects. Sleep-promoting effects were delayed, with a slight initial alerting effect.

Citation: Schneider-Helmert D, Schoenenberger GA. The influence of synthetic DSIP (delta-sleep-inducing-peptide) on disturbed human sleep.. Experientia 1981.

International journal of clinical pharmacology, therapy, and toxicology · 1981 · PMID 6895513 · PubMed

This double-blind crossover study compared intravenous DSIP with placebo in healthy human volunteers. DSIP increased sleep shortly after administration and was followed by faster sleep onset and better sleep efficiency that night, without classic sedative effects. It was well tolerated, with no psychological, physiological, or biochemical side effects observed in this study.

Citation: Schneider-Helmert D, Gnirss F, Monnier M, Schenker J, Schoenenberger GA. Acute and delayed effects of DSIP (delta sleep-inducing peptide) on human sleep behavior.. International journal of clinical pharmacology, therapy, and toxicology 1981.

Pflugers Archiv : European journal of physiology · 1978 · PMID 568769 · PubMed

This animal study identified DSIP’s chemical structure and compared synthetic DSIP with related peptides infused into rabbits’ brains. Synthetic DSIP specifically increased slow-wave and spindle patterns in brain electrical recordings compared with controls and the other peptides. Its activity depended on its precise chemical structure.

Citation: Schoenenberger GA, Maier PF, Tobler HJ, Wilson K, Monnier M. The delta EEG (sleep)-inducing peptide (DSIP). XI. Amino-acid analysis, sequence, synthesis and activity of the nonapeptide.. Pflugers Archiv : European journal of physiology 1978.

Proceedings of the National Academy of Sciences of the United States of America · 1977 · PMID 265572 · PubMed

This animal study characterized DSIP isolated from rabbits and compared synthetic DSIP with related peptides infused into rabbits’ brains under double-blind conditions. Only synthetic DSIP significantly and specifically increased or induced slow-wave and spindle patterns in brain electrical recordings.

Citation: Schoenenberger GA, Monnier M. Characterization of a delta-electroencephalogram (-sleep)-inducing peptide.. Proceedings of the National Academy of Sciences of the United States of America 1977.

ClinicalTrials.gov · 2027 · NCT07706361 · ClinicalTrials.gov

This registered human trial plans to compare the X39 patch with a placebo patch to assess changes in blood levels of GHK and GHK-Cu in healthy adults. It has not yet begun recruiting, and no results are reported.

Population / model

GHK and GHK-Cu Blood Levels

Citation: LifeWave, Inc.. A Two-part Study Investigating the Effect of the X39 Patch on Circulating Blood Levels of GHK and GHK-Cu in a Healthy Adult Population. ClinicalTrials.gov 2027.

Biogerontology · 2026 · PMID 42084774 · BioNex Evolve (PubMed-indexed)

This animal study examined GHK-Cu and aging in the roundworm Caenorhabditis elegans. GHK-Cu significantly extended lifespan and improved several aging-related measures, including movement and resistance to heat and oxidative stress. These effects involved preserved mitochondrial function and activation of the DAF-16 and SKN-1 pathways; human aging was not studied.

Citation: Wen H, Zhao K, Luo X, Pu J, Li Y, Dou Y, He J, Nie X, Ke Y, Zhou W. The GHK-Cu delays aging in Caenorhabditis elegans via coordinated regulation of mitochondrial function and activation of DAF-16/SKN-1 pathways. Biogerontology 2026.

European journal of pharmacology · 2026 · PMID 41997403 · BioNex Evolve (PubMed-indexed)

This animal study tested GHK-Cu in zebrafish larvae with chemically induced acute inflammation. GHK-Cu reduced immune-cell migration, decreased pro-inflammatory signals, increased an anti-inflammatory signal, and reduced oxidative stress. It also reduced activity in the JAK1 signaling pathway.

Citation: Hu J, Zhang C, Wang F. Glycyl-L-histidyl-L-lysine-Cu2<sup>+</sup> (GHK-Cu) Attenuates CuSO<sub>4</sub> or LPS induced-inflammation in Zebrafish larvae model. European journal of pharmacology 2026.

ClinicalTrials.gov · 2026 · NCT07437586 · ClinicalTrials.gov

This human trial is testing whether GHK-Cu gel can safely speed healing of small skin wounds in healthy adults compared with a matching gel without GHK-Cu. The trial is recruiting, and no results are reported.

Population / model

Acute Standardized Cutaneous Wounds (Punch-biopsy Wounds)

Citation: Hudson Biotech. A Phase 2, Randomized, Double-Blind, Vehicle-Controlled, Split-Wound Study of Topical GHK-Cu (Copper(II)-Peptide Complex) Gel to Accelerate Re-Epithelialization of Standardized Acute Skin Wounds in Healthy Adults. ClinicalTrials.gov 2026.

BioImpacts · 2025 · PMID 39963574 · BioNex Evolve (PubMed-indexed)

This review examines laboratory cell studies of GHK and its derivatives, including GHK-Cu, as potential anti-wrinkle ingredients. Cell findings support anti-wrinkle activity, but the authors highlight an absence of clinical studies of GHK-Cu and Pal-GHK. They also describe limitations in skin penetration and formulation stability.

Citation: Mortazavi SM, Mohammadi Vadoud SA, Moghimi HR. Topically applied GHK as an anti-wrinkle peptide: Advantages, problems and prospective.. BioImpacts 2025.

Bioconjugate chemistry · 2025 · PMID 40123442 · BioNex Evolve (PubMed-indexed)

This laboratory study tested newly made compounds linking GHK to hyaluronic acid and binding them to copper; it was not a human observational study. The compounds enhanced the components' chemical and biological properties in laboratory tests. Copper promoted production and release of factors involved in nerve support, blood vessel growth, and bone formation.

Citation: Greco V, Lanza V, Tomasello B, Naletova I, Cairns WRL, Sciuto S, Rizzarelli E. Copper Complexes with New Glycyl-l-histidyl-l-lysine-Hyaluronan Conjugates Show Antioxidant Properties and Osteogenic and Angiogenic Synergistic Effects.. Bioconjugate chemistry 2025.

Colloids and surfaces. B, Biointerfaces · 2025 · PMID 40716276 · BioNex Evolve (PubMed-indexed)

This animal and laboratory study tested a soft-tissue filler containing GHK-Cu attached to hydroxyapatite microspheres in experimental inflammation models. The filler reduced inflammatory markers and reactive oxygen molecules, increased activity of an antioxidant enzyme, and showed significant collagen deposition. These findings support its anti-inflammatory and antioxidant properties in the tested models.

Citation: Hu D, Zhang X, Gong S, Ma W, Cheng B, Yang J, Yan L, Li B, Qiu T, Wang X. An injectable hydroxyapatite microsphere filler loaded with GHK-Cu tripeptide for anti-Inflammatory and antioxidant. Colloids and surfaces. B, Biointerfaces 2025.

Molecules (Basel, Switzerland) · 2025 · PMID 39795193 · BioNex Evolve (PubMed-indexed)

This review examined methods for studying how GHK-Cu crosses the skin barrier, either alone or enclosed in tiny fat-based carriers called liposomes. GHK-Cu has limited skin penetration, and liposomes may improve it. However, the review found little research on transport of liposome-encapsulated GHK-Cu, highlighting a need for better assessment methods.

Citation: Ogórek K, Nowak K, Wadych E, Ruzik L, Timerbaev AR, Matczuk M. Are We Ready to Measure Skin Permeation of Modern Antiaging GHK-Cu Tripeptide Encapsulated in Liposomes?. Molecules (Basel, Switzerland) 2025.

Redox biology · 2024 · PMID 38879894 · BioNex Evolve (PubMed-indexed)

This animal and laboratory study tested GHK-Cu in mice with silica-induced lung disease and in cultured immune cells. GHK-Cu bound to the protein peroxiredoxin 6 and reduced lung inflammation and scarring in mice without significant whole-body toxicity. These effects were partly linked to reduced oxidative stress in lung immune cells.

Citation: Bian Y, Deng M, Liu J, Li J, Zhang Q, Wang Z, Liao L, Miao J, Li R, Zhou X, Hou G. The glycyl-l-histidyl-l-lysine-Cu2+ tripeptide complex attenuates lung inflammation and fibrosis in silicosis by targeting peroxiredoxin 6.. Redox biology 2024.

Metallomics : integrated biometal science · 2024 · PMID 38599632 · BioNex Evolve (PubMed-indexed)

This laboratory study tested GHK in central nervous system cells and protein experiments exposed to copper or zinc. GHK prevented metal-induced cell death and protein clumping, and it also reversed existing protein clumps. It reduced copper-related toxicity under inflammatory conditions and protected against toxicity involving copper and paraquat.

Citation: Min JH, Sarlus H, Harris RA. Glycyl-l-histidyl-l-lysine prevents copper- and zinc-induced protein aggregation and central nervous system cell death in vitro.. Metallomics : integrated biometal science 2024.

Journal of cachexia, sarcopenia and muscle · 2023 · PMID 36905132 · BioNex Evolve (PubMed-indexed)

This study measured blood GHK in people with chronic obstructive pulmonary disease and tested GHK-Cu in smoke-exposed mice and cultured muscle cells. Human GHK levels were lower than in healthy controls and were associated with muscle mass. In animal and laboratory experiments, GHK-Cu protected against muscle dysfunction through activation of SIRT1, a protein involved in cellular regulation.

Citation: Deng M, Zhang Q, Yan L, Bian Y, Li R, Gao J, Wang Y, Miao J, Li J, Zhou X, Hou G. Glycyl-l-histidyl-l-lysine-Cu2+ rescues cigarette smoking-induced skeletal muscle dysfunction via a sirtuin 1-dependent pathway.. Journal of cachexia, sarcopenia and muscle 2023.

ClinicalTrials.gov · 2023 · NCT05932732 · ClinicalTrials.gov

This completed, open-label human study assessed Hydrafacial treatments for skin quality, hydration, skin barrier function, and satisfaction in healthy adults across different skin types. The abstract describes the study plan but reports no results.

Population / model

Cutis Laxa Facialis; Xeroderma

Citation: Austin Institute for Clinical Research. A Phase IV Open-label Trial Assessing the Impact on Skin Quality, Hydration, and Barrier of Three (3) Hydrafacial Treatments in Adults of Fitzpatrick Skin Types I-VI. ClinicalTrials.gov 2023.

Frontiers in molecular biosciences · 2022 · PMID 35936787 · BioNex Evolve (PubMed-indexed)

This animal and laboratory study tested GHK-Cu in cigarette-smoke-exposed mice and cultured human lung cells. GHK-Cu reduced emphysema-related lung damage, inflammation, and oxidative stress in mice, and also reduced oxidative stress in the cells. These effects involved reduced inflammatory signaling and increased activity of antioxidant-defense pathways.

Citation: Zhang Q, Yan L, Lu J, Zhou X. Glycyl-L-histidyl-L-lysine-Cu2+ attenuates cigarette smoke-induced pulmonary emphysema and inflammation by reducing oxidative stress pathway.. Frontiers in molecular biosciences 2022.

Inorganic chemistry · 2021 · PMID 34730942 · BioNex Evolve (PubMed-indexed)

This laboratory study examined how copper, the peptide GHK, and human serum albumin bind together, rather than studying outcomes in people. It identified complexes linking copper-bound GHK to specific sites on albumin. These complexes may help transport exchangeable copper and the functional form of GHK in the blood.

Citation: Bossak-Ahmad K, Bal W, Frączyk T, Drew SC. Ternary Cu2+ Complexes of Human Serum Albumin and Glycyl-l-histidyl-l-lysine.. Inorganic chemistry 2021.

Aging Pathobiology and Therapeutics · 2020 · PMID 35083444 · BioNex Evolve (PubMed-indexed)

This review examined the potential anti-aging effects of GHK and its copper-bound form, GHK-Cu, drawing on laboratory and animal research. It describes wound-healing, tissue-remodeling, antioxidant, and anti-inflammatory effects, while preliminary observations suggest GHK may partly reverse cognitive impairment in aging mice. The authors call for further preclinical and human studies.

Citation: Dou Y, Lee A, Zhu L, Morton J, Ladiges W. The potential of GHK as an anti-aging peptide.. Aging Pathobiology and Therapeutics 2020.

Life sciences · 2020 · PMID 31809714 · BioNex Evolve (PubMed-indexed)

This animal study tested GHK-Cu in mice with bleomycin-induced lung scarring. GHK-Cu reduced inflammation, collagen buildup, and scarring-related tissue changes, while partially preventing cell changes that contribute to fibrosis. The authors linked these protective effects to pathways involved in oxidative stress, inflammation, and scar formation.

Citation: Ma WH, Li M, Ma HF, Li W, Liu L, Yin Y, Zhou XM, Hou G. Protective effects of GHK-Cu in bleomycin-induced pulmonary fibrosis via anti-oxidative stress and anti-inflammation pathways. Life sciences 2020.

Materials science & engineering. C, Materials for biological applications · 2019 · PMID 31500015 · BioNex Evolve (PubMed-indexed)

This lab study examined titanium coatings containing GHK-Cu-loaded nanoparticles, including their interactions with bacteria and cells. Copper release depended on surface acidity, and controlled release inhibited bacterial attachment while showing good compatibility with cells.

Citation: Ning C, Jiajia J, Meng L, Hongfei Q, Xianglong W, Tingli L. Electrophoretic deposition of GHK-Cu loaded MSN-chitosan coatings with pH-responsive release of copper and its bioactivity. Materials science & engineering. C, Materials for biological applications 2019.

International Journal of Molecular Sciences · 2018 · editorial

This review examined regenerative and protective actions of GHK-Cu in relation to new gene data; the title does not specify the populations or experimental models involved. The abstract was not available, so results are not summarized.

Population / model

Summary of lab, animal and small cosmetic studies

Limitations

Narrative review; limited controlled human data.

Citation: Pickart L, Margolina A.. Regenerative and protective actions of the GHK-Cu peptide in the light of the new gene data. International Journal of Molecular Sciences 2018.

Oncotarget · 2016 · PMID 27517151 · BioNex Evolve (PubMed-indexed)

This laboratory and animal study tested GHK-Cu in immune cells and mice with acute lung injury triggered by a bacterial component. GHK-Cu reduced oxidative stress and inflammatory signals. In mice, it also lessened lung tissue damage and the buildup of inflammatory cells in the lungs.

Citation: Park JR, Lee H, Kim SI, Yang SR. The tri-peptide GHK-Cu complex ameliorates lipopolysaccharide-induced acute lung injury in mice. Oncotarget 2016.

Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2015 · PMID 25731775 · BioNex Evolve (PubMed-indexed)

This animal study tested GHK-Cu after knee ligament reconstruction in rats. It temporarily improved knee stability and, in one treatment group, graft stiffness, but did not significantly improve graft breaking strength, walking measures, or tissue-healing scores. The benefits did not persist after treatment stopped.

Citation: Fu SC, Cheuk YC, Chiu WY, Yung SH, Rolf CG, Chan KM. Tripeptide-copper complex GHK-Cu (II) transiently improved healing outcome in a rat model of ACL reconstruction. Journal of orthopaedic research : official publication of the Orthopaedic Research Society 2015.

Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery · 2013 · PMID 23744835 · PubMed

This animal study tested topical GHK-Cu on surgically created skin flaps in rats previously exposed to radiation. Compared with control ointment, GHK-Cu showed no difference in tissue affected by poor blood supply, blood vessel number or area, or expression of the blood vessel growth signal VEGF.

Citation: Parker NP, Ardeshirpour F, Schmechel SC, Lassig AA. Effects of topical copper tripeptide complex on wound healing in an irradiated rat model.. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery 2013.

Oxidative medicine and cellular longevity · 2012 · PMID 22666519 · BioNex Evolve (PubMed-indexed)

This review discusses GHK and GHK-Cu research, including human tissue and gene-expression findings, in relation to aging and cognitive health. It describes antioxidant, anti-inflammatory, and gene-regulating properties and proposes GHK as a possible agent against age-related nerve degeneration and cognitive decline. The abstract does not report demonstrated cognitive benefits in people.

Citation: Pickart L, Vasquez-Soltero JM, Margolina A. The human tripeptide GHK-Cu in prevention of oxidative stress and degenerative conditions of aging: implications for cognitive health. Oxidative medicine and cellular longevity 2012.

Journal of biomaterials science. Polymer edition · 2008 · PMID 18644225 · PubMed

This review summarizes research on GHK and its copper-bound form, GHK-Cu, in cells, experimental models, and humans. It reports effects on inflammation, tissue repair, and wound healing. Controlled studies of aging skin reported improved firmness and elasticity and reduced wrinkles, sun damage, and excess pigmentation.

Citation: Pickart L. The human tri-peptide GHK and tissue remodeling.. Journal of biomaterials science. Polymer edition 2008.

Archives of facial plastic surgery · 2006 · PMID 16847171 · PubMed

This randomized human study compared skin-care regimens with or without GHK-Cu after carbon dioxide laser resurfacing around the mouth. GHK-Cu offered no significant improvement in redness resolution or objectively assessed wrinkles and overall skin quality compared with the control regimen. However, patient satisfaction was significantly higher with GHK-Cu.

Citation: Miller TR, Wagner JD, Baack BR, Eisbach KJ. Effects of topical copper tripeptide complex on CO2 laser-resurfaced skin.. Archives of facial plastic surgery 2006.

Life sciences · 2000 · PMID 11045606 · PubMed

This laboratory study tested GHK-Cu in cultured skin fibroblasts, cells that make and maintain connective tissue. GHK-Cu increased production of the tissue-remodeling enzyme MMP-2 and release of its natural inhibitors. Copper alone reproduced the MMP-2 effect, but GHK without copper did not.

Citation: Siméon A, Emonard H, Hornebeck W, Maquart FX. The tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+ stimulates matrix metalloproteinase-2 expression by fibroblast cultures.. Life sciences 2000.

Advances in experimental medicine and biology · 1990 · PMID 2244543 · PubMed

This lab study examined whether GHK-Cu reduces iron-driven damage to fats in experiments involving ferritin, an iron-storage protein. GHK-Cu inhibited this damage only when ferritin was the iron source and also inhibited iron release from ferritin. The authors proposed that blocking ferritin iron release may contribute to its wound-healing effects.

Citation: Miller DM, DeSilva D, Pickart L, Aust SD. Effects of glycyl-histidyl-lysyl chelated Cu(II) on ferritin dependent lipid peroxidation.. Advances in experimental medicine and biology 1990.

The lancet. Diabetes & endocrinology · 2026 · PMID 42251859 · BioNex Evolve (PubMed-indexed)

This completed randomized trial compared combined cagrilintide and semaglutide with the individual medicines in adults with type 2 diabetes and overweight or obesity. In the primary comparison, the combination produced a statistically significantly greater reduction in HbA1c, a measure of long-term blood sugar, than semaglutide alone. The supplied abstract cuts off during the safety results.

Citation: Buse JB, Bajaj HS, Dalskov SM, Donaldson L, Hansen Duus HH, Fabricius TW, Haluzík M, Lingvay I, Pedersen SD, Pratley RE, Jain AB. Cagrilintide-semaglutide (CagriSema) versus semaglutide or cagrilintide in people with type 2 diabetes (REIMAGINE 2): a double-blind, randomised, controlled, phase 3 study. The lancet. Diabetes & endocrinology 2026.

Pharmaceutical research · 2026 · PMID 42687069 · BioNex Evolve (PubMed-indexed)

This review examined how semaglutide is absorbed and approaches to improving oral delivery, rather than reporting a new experiment. Absorption of oral semaglutide remains very low because of breakdown in the digestive tract and barriers to uptake. Emerging delivery technologies may improve absorption and expand the uses of oral peptide therapies.

Citation: Vahora S, Shah V, Patel B. Semaglutide Bioavailability: Limitations, Formulation Innovation and Future Opportunities. Pharmaceutical research 2026.

PloS one · 2026 · PMID 42507673 · BioNex Evolve (PubMed-indexed)

This registered human trial protocol describes a planned comparison of gradual semaglutide withdrawal with abrupt stopping in people with obesity who had lost weight and reached a weight plateau. Researchers will assess weight regain and measures related to heart and metabolic health. No results are reported; reduced weight regain with gradual withdrawal is a hypothesis.

Citation: Yevusiak T, Weisman A, Retnakaran R, Wharton S, Drucker DJ, Kramer CK. Impact of semaglutide withdrawal on cardiometabolic profile and physiology of energy balance: Recovery effects after semaglutide termination - The REST trial study protocol. PloS one 2026.

Diabetes · 2026 · PMID 42390988 · BioNex Evolve (PubMed-indexed)

This animal study examined sex-specific effects of semaglutide on muscle in mice with severe obesity caused by leptin deficiency. Body weight and food intake decreased similarly in both sexes, but males had minor muscle loss while females had none. Muscle force remained intact in both sexes.

Citation: Rout S, Karasawa T, Watanabe S, Chaix A, Drummond MJ, Funai K, Choi RH. Females Are Completely Resistant to Semaglutide-Induced Muscle Loss in ob/ob Mice. Diabetes 2026.

Clinical obesity · 2026 · PMID 42584177 · BioNex Evolve (PubMed-indexed)

This systematic review and meta-analysis examined depression, anxiety, and suicidal thoughts or attempts in people receiving semaglutide. It found no statistically significant increase compared with placebo or other treatments. However, substantial differences between studies and risk of bias limited certainty, so the findings do not prove an absence of psychiatric risk.

Citation: Bhaduri G, Roy S, Kalia A, Gokalani R, Saboo B. Burden and Risk of Depression in Patients Receiving Semaglutide: A Systematic Review and Meta-Analysis. Clinical obesity 2026.

Diabetes, obesity & metabolism · 2026 · PMID 42225300 · BioNex Evolve (PubMed-indexed)

This study indirectly compared oral and injectable semaglutide using separate trials in adults with obesity or overweight and weight-related health problems. The analysis suggested comparable weight-management effectiveness, with broadly comparable safety profiles. It was not a direct head-to-head trial.

Citation: Plotkin M, Ivkovic M, Smith I, Rathor N, Chowdhury R, Hodkinson A, Kushner RF. Semaglutide 25 mg Oral Versus Semaglutide 2.4 mg Injectable: An Indirect Treatment Comparison of Weight Loss Outcomes. Diabetes, obesity & metabolism 2026.

Journal of chromatography. B, Analytical technologies in the biomedical and life sciences · 2026 · PMID 42664897 · BioNex Evolve (PubMed-indexed)

This review compared laboratory methods for identifying and measuring semaglutide in pharmaceutical products and biological samples. It presented chromatography, which separates a sample’s components, as the most effective, sensitive, and reliable approach, while also discussing alternative methods.

Citation: Kavibharathi V, Thirusha KM, Vijayadevan G, Vijayakumar R, Nalini CN. Analytical methods for the determination of semaglutide in pharmaceutical formulations and biological matrices: A comprehensive review. Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 2026.

The American journal of psychiatry · 2026 · PMID 42522065 · BioNex Evolve (PubMed-indexed)

This randomized human trial compared oral semaglutide with placebo in adults seeking treatment for moderate to severe alcohol use disorder. Semaglutide did not significantly reduce laboratory-measured alcohol craving or average daily drinking, but significantly reduced heavy drinking days. It also reduced drinking on drinking days, everyday craving, alcohol-related consequences, and cannabis-use days.

Citation: Schacht JP, Sakai JT, Raymond K, Shelton R. Oral Semaglutide for Alcohol Use Disorder: A Randomized Clinical Trial. The American journal of psychiatry 2026.

Journal of clinical pharmacology · 2026 · PMID 42612051 · BioNex Evolve (PubMed-indexed)

This systematic review combined observational human studies examining semaglutide and nonarteritic anterior ischemic optic neuropathy, an optic nerve condition linked to reduced blood flow. Semaglutide use was associated with higher risk overall and among people with diabetes, but the association was not statistically significant among overweight or obese people. The authors described a possible association requiring randomized trials for clearer conclusions.

Citation: Khani E, Asham H, Rezabakhsh A, Babaei S, Entezari-Maleki T. Semaglutide-Induced Nonarteritic Anterior Ischemic Optic Neuropathy: A Systematic Review and Meta-Analysis. Journal of clinical pharmacology 2026.

Cell reports. Medicine · 2026 · PMID 42314683 · BioNex Evolve (PubMed-indexed)

This animal study examined semaglutide’s effects on bones in obese male mice. Treated mice had lower thighbone mass, stiffness, and strength, with more pronounced effects than in mice undergoing matched calorie restriction. After semaglutide was discontinued, these bone measures did not differ from controls; whether similar effects occur in humans requires investigation.

Citation: Eisner K, Jeromson S, Tahboub K, Zimmerman EA, Wright DC. Negative effects of semaglutide on bone in obese mice. Cell reports. Medicine 2026.

Expert opinion on drug delivery · 2026 · PMID 42288971 · BioNex Evolve (PubMed-indexed)

This review examined semaglutide formulations and strategies to improve oral absorption, rather than reporting a new experiment. Breakdown in the digestive tract and barriers to uptake limit absorption. The authors proposed gut-targeted delivery and protective coatings as promising approaches intended to reduce breakdown and improve intestinal uptake.

Citation: Nayak S, Dessai AD, Nayak UY. Current trends in semaglutide therapy and strategies to improve its bioavailability. Expert opinion on drug delivery 2026.

Pharmaceuticals (Basel, Switzerland) · 2026 · PMID 42653733 · BioNex Evolve (PubMed-indexed)

This systematic review examined oral and injected semaglutide in adults with obesity or overweight with a weight-related condition. Across separate studies, both forms produced comparable weight loss and improved blood sugar, blood pressure, and blood fats; oral treatment was preferred by people averse to needles. Direct head-to-head trials were lacking, and robust comparative trials are needed.

Citation: La Vignera S, Condorelli RA. Oral vs. Subcutaneous Semaglutide for Obesity Treatment: A Systematic Review of Efficacy, Safety, and Patient-Oriented Outcomes. Pharmaceuticals (Basel, Switzerland) 2026.

The lancet. Diabetes & endocrinology · 2026 · PMID 42567173 · BioNex Evolve (PubMed-indexed)

This prespecified pooled analysis examined semaglutide’s kidney effects in randomized human trials involving people with chronic kidney disease or cardiovascular disease, with and without diabetes. Semaglutide reduced the combined risk of major kidney outcomes and cardiovascular death compared with placebo; kidney outcomes also improved when cardiovascular death was excluded. Safety findings were broadly similar between groups.

Citation: Mann JFE, Badve SV, Baeres FMM, Belmar N, Brown-Frandsen K, Buse JB, Colhoun HM, Deanfield JE, Engelmann MDM, Hovingh GK, Idorn T, Lincoff AM, Lingvay I, Mahaffey KW, McGuire DK, Pratley RE, Rasmussen S, Rossing P, Sattar N, Tuttle KR, Perkovic V. Effect of semaglutide on kidney outcomes in the SELECT, FLOW, and SOUL trials: a prespecified pooled analysis. The lancet. Diabetes & endocrinology 2026.

Biomedicines · 2026 · PMID 42652226 · BioNex Evolve (PubMed-indexed)

This review examined semaglutide’s effectiveness and safety in women with polycystic ovary syndrome. Preliminary, mostly low-quality evidence suggested potential benefits for weight, metabolic health, and menstrual regularity; digestive side effects were most common and generally mild to moderate and temporary. Larger randomized trials are needed to confirm reproductive outcomes and long-term safety.

Citation: La Vignera S, Condorelli RA. Efficacy and Safety of Semaglutide in Patients with Polycystic Ovary Syndrome: A Scoping Review. Biomedicines 2026.

Endocrine · 2026 · PMID 42603240 · BioNex Evolve (PubMed-indexed)

This systematic review and meta-analysis examined blood pressure-related adverse events in randomized trials involving people with type 2 diabetes or obesity. Tirzepatide was associated with fewer high blood pressure events but more low blood pressure events. Semaglutide showed no statistically significant association with either type of event overall.

Citation: Chen QX, Zhou XY, Wu Q, Xie JJ, Xu Y, Teng FY, Guo M. Effect of tirzepatide and semaglutide on blood pressure: A systematic review and meta-analysis. Endocrine 2026.

Medicina (Kaunas, Lithuania) · 2026 · PMID 42654433 · BioNex Evolve (PubMed-indexed)

This systematic review examined whether the day of semaglutide or tirzepatide administration affects outcomes in adults with type 2 diabetes or obesity. No studies directly compared different weekdays for the injectable drugs, so current evidence does not support an optimal day. Suggestions that flexible schedules may help adherence and tolerability came mainly from indirect evidence and expert opinion.

Citation: La Vignera S, Condorelli RA. Is There a Better Day of the Week to Administer Semaglutide or Tirzepatide? A Systematic Literature Review. Medicina (Kaunas, Lithuania) 2026.

Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde · 2026 · PMID 42348481 · BioNex Evolve (PubMed-indexed)

This review examined clinical trials reporting retinal blood-vessel events in people with type 2 diabetes or obesity receiving semaglutide. These events, especially retinal artery blockages, were rare but reported more often in semaglutide groups; reduced-blood-flow injuries to the optic nerve were also reported more often. The authors called for further investigation through large registry studies.

Citation: Choujaa Goudira S, Højlund K, Grauslund J. The Risk of Retinal Vascular Events in Patients Using Semaglutide: A Scoping Review. Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde 2026.

Metabolites · 2026 · PMID 42646322 · BioNex Evolve (PubMed-indexed)

This review examines how resmetirom and semaglutide may affect metabolic changes linked to inflammation and scarring in metabolic fatty liver disease. Resmetirom may act mainly within the liver, while semaglutide may improve the liver’s metabolic environment indirectly through effects elsewhere in the body. Many specific mechanisms remain incompletely understood in humans.

Citation: Toshikuni N. Therapeutic Mechanisms of Resmetirom and Semaglutide in MASLD/MASH: A Review of Inflammatory and Fibrotic Metabolites. Metabolites 2026.

Clinical journal of the American Society of Nephrology : CJASN · 2026 · PMID 42308057 · BioNex Evolve (PubMed-indexed)

This randomized trial studied semaglutide in adults with chronic kidney disease and overweight or obesity, without type 2 diabetes. Compared with placebo, semaglutide reduced lean body mass and fat mass, but these changes did not correlate with changes in estimated or measured kidney filtration. Semaglutide also reduced fluid outside cells and blood pressure, and these changes were correlated.

Citation: Heerspink HJL, Soler M, Beernink JM, Jongs N, Cigarran S, Cigarran S, Cruzado JM, Puchades MJ, López-Martínez M, López-Martínez M, Apperloo E, Waanders F, Laverman GD, van der Aart-van der Beek A, van Beek AP, Verhave JC, Ahmed SB, Schmieder RE, Wanner C, Cherney DZI, Górriz JL. Effects of Semaglutide on Body Composition and GFR: A Prespecified Analysis of the SMART Trial. Clinical journal of the American Society of Nephrology : CJASN 2026.

Molecular metabolism · 2026 · PMID 42364710 · BioNex Evolve (PubMed-indexed)

This animal study examined long-term semaglutide treatment and taste responses in mice with diet-induced obesity. Semaglutide produced substantial weight loss without detectably impairing taste responses, sweet taste sensitivity, or taste-cell features. Increased engagement with sweet solutions suggested changes in motivation rather than taste perception.

Citation: Acosta AA, Ellis H, Hsu FY, Yee KK, de Lartigue G, Alhadeff AL. Chronic semaglutide alters ingestive behavior without impairing taste function in mice. Molecular metabolism 2026.

International journal of obesity (2005) · 2026 · PMID 42668312 · BioNex Evolve (PubMed-indexed)

This systematic review combined randomized human trials of injected semaglutide in adults with overweight or obesity without diabetes. Compared with placebo, semaglutide significantly reduced body weight, waist circumference, and the inflammation marker C-reactive protein. Serious adverse events did not differ significantly between groups, and the authors called for longer-term studies.

Citation: Milluzzo A, Oteri V, Manuella L, Pulvirenti A, Frittitta L. Effects of subcutaneous semaglutide on weight loss and inflammatory markers in adults with overweight or obesity without diabetes: a systematic review and meta-analysis. International journal of obesity (2005) 2026.

The American journal of cardiology · 2026 · PMID 42342009 · BioNex Evolve (PubMed-indexed)

This systematic review combined randomized trials comparing semaglutide with placebo in adults with obesity and heart failure with preserved pumping function. Semaglutide was associated with improved symptoms, lower levels of a blood marker of heart strain, and a lower risk of hospitalization for heart failure.

Citation: Ceravolo R, Lucà F, Gulizia MM, Nardi F, Grimaldi M, Gelsomino S. Semaglutide for the Silent Phenotype: A Translational Signal in Obesity-Driven HFpEF. The American journal of cardiology 2026.

Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2026 · PMID 41728915 · BioNex Evolve (PubMed-indexed)

This analysis of a randomized human trial examined infections in people with type 2 diabetes and chronic kidney disease. Compared with placebo, semaglutide reduced the combined risk of serious infection, infection-related hospitalization, or death from any cause. Serious infections and COVID-19 events were also less frequent with semaglutide.

Citation: Rayner B, Mahaffey KW, Mann JFE, Pratley RE, Rossing P, Belmar N, Bosch-Traberg H, Jeppesen OK, Tran MC, Chernin G, Tuttle KR. Effect of semaglutide on COVID-19 and other infections: an analysis from the FLOW randomized clinical trial. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 2026.

Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and Gynaecology · 2026 · PMID 42495930 · BioNex Evolve (PubMed-indexed)

This observational human study compared weight-loss surgery, semaglutide, and a structured lifestyle programme in patients receiving fertility-preserving treatment for endometrial cancer. Surgery was associated with the greatest initial weight loss, while the lifestyle group had less weight regain, more stable metabolic improvements, and the highest complete tumour remission rate. Participants were not randomly assigned to these approaches.

Citation: Wei Y, Gong Y, Gong J, Zeng H, Zhong Z, Xiong Y, Li X. Comparison of lifestyle, surgery, and semaglutide for weight management in endometrial cancer: a prospective observational study. Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and Gynaecology 2026.

Medicine · 2026 · PMID 42536519 · BioNex Evolve (PubMed-indexed)

This systematic review combined randomized trials of semaglutide in adults with overweight or obesity without type 2 diabetes. Semaglutide produced greater weight loss than placebo, but digestive side effects and stopping treatment because of side effects were more common. Serious adverse events were rare, and longer-term safety and lasting weight loss need further study.

Citation: Naz F, Qaiser F, Mumtaz A, Din SU, Mustafa A, Ullah A, Perveen A, Malik J. Effectiveness & safety of semaglutide in weight reduction in obese nondiabetic patients: A systematic review and meta-analysis. Medicine 2026.

Circulation · 2026 · PMID 42610271 · BioNex Evolve (PubMed-indexed)

This planned analysis of a randomized human trial examined inflammation in people with cardiovascular disease and overweight or obesity, but not diabetes. Semaglutide lowered the inflammation marker hsCRP and reduced major cardiovascular events across baseline hsCRP groups. The findings suggest that reduced inflammation may partly contribute to semaglutide’s cardiovascular benefits.

Citation: Plutzky J, Bogdański P, Colhoun HM, Dagdelen S, Deanfield JE, Emerson SS, Hovingh GK, Kahn SE, Ekström K, Latkovskis G, Lehrke M, Hardt-Lindberg S, Lingvay I, Nicholls SJ, Kalayci Oral T, Terns PP, Rasmussen S, Ridker PM, Ryan DH, Lincoff AM. Effect of Semaglutide on the Inflammatory Biomarker High-Sensitivity CRP in Patients With Established Cardiovascular Disease and Overweight or Obesity in SELECT: A Prespecified Secondary Analysis. Circulation 2026.

Molecular biology reports · 2026 · PMID 42573665 · BioNex Evolve (PubMed-indexed)

This review examined semaglutide’s potential brain-protective effects in preclinical disease models and human studies. Preclinical studies reported reduced inflammation and selected improvements, but human Alzheimer’s trials did not meet their main cognitive goals despite improvements in some biological markers. Observational studies linked semaglutide or related drugs to lower dementia risk, but did not establish causation.

Citation: Mukim RD, Xu Y, Evola V, Parmar MS. Semaglutide as a potential neuroprotective agent for neurological and neurodegenerative disorders: Mechanisms, preclinical evidence, and translational challenges and opportunities. Molecular biology reports 2026.

JCI insight · 2026 · PMID 42262870 · BioNex Evolve (PubMed-indexed)

This animal study tested whether a ketone ester could prevent semaglutide-related muscle loss in obese mice with impaired glucose control. Adding the ketone ester preserved muscle mass and function without compromising fat loss and prevented changes in genes related to muscle wasting and cellular energy production. These findings have not yet been established in humans.

Citation: Abuetabh Y, Schmidt MA, Naganuma M, Vaka R, El-Ghiaty MA, Braun S, Kwan EA, Zolondek MC, Sahid D, Khan L, Shandal RK, Trudeau AL, Li Y, Malik SO, Sun Q, Roth DK, Morales-Llamas DY, Levasseur JL, Ferdaoussi M, Fahlman RP, Dyck JR. Semaglutide-induced loss of skeletal muscle mass is blunted by co-administration of ketone esters. JCI insight 2026.

Clinical obesity · 2026 · PMID 42670242 · BioNex Evolve (PubMed-indexed)

This systematic review combined trials and observational studies comparing tirzepatide with semaglutide in adults with overweight or obesity. Tirzepatide was associated with greater weight loss and improved long-term blood sugar levels, but serious adverse events were more frequent. Overall side effects, digestive side effects, and treatment discontinuation due to adverse events did not differ significantly.

Citation: Paccola GP, de Oliveira RF, Mochetti MM, Razera FPM, Vecchi R, Montanher RCP. Comparative Efficacy of Tirzepatide Versus Semaglutide for Weight Loss in Adults With Overweight or Obesity: A Systematic Review and Meta-Analysis of Head-to-Head Studies. Clinical obesity 2026.

Biochemical pharmacology · 2026 · PMID 42315078 · BioNex Evolve (PubMed-indexed)

This animal and lab study tested semaglutide in mice with experimentally induced lung scarring and in cultured mouse lung cells. Semaglutide reduced lung scarring, oxidative stress, and cellular aging in mice and inhibited cellular aging in culture. These effects involved the Sirt1/HSF1 pathway and increased heat shock proteins, and were weakened by blocking Sirt1 or silencing HSF1.

Citation: Qian Z, Shuang L, Yu-Yang L, Min-Lin L, Chong-Mei H, Min-Hui L, Wei L, Si-Yuan T. Semaglutide exerts anti-pulmonary fibrosis effects by inhibiting cellular senescence through activation of the Sirt1/HSF1/HSPs pathway. Biochemical pharmacology 2026.

Postgraduate medicine · 2026 · PMID 42286992 · BioNex Evolve (PubMed-indexed)

This review discusses oral semaglutide for obesity management in adults, drawing on human clinical trials and the authors’ clinical experience. It reports weight loss comparable to injectable GLP-1 medicines, alongside improvements in heart and metabolic risk factors. It also discusses absorption requirements, treatment adherence, and side effects.

Citation: Rubino D, Wharton S, Knight MG, Aroda VR. Evidence-informed guidance for the clinical use of oral semaglutide in obesity management. Postgraduate medicine 2026.

Journal of diabetes and its complications · 2026 · PMID 42679726 · BioNex Evolve (PubMed-indexed)

This secondary analysis of a randomized human trial examined semaglutide and empagliflozin effects on blood-vessel lining function in people with type 2 diabetes. Semaglutide improved a measure of vessel function from baseline, but not significantly compared with placebo; empagliflozin had no effect on that measure. Blood markers showed mixed changes rather than consistent improvement.

Citation: Gullaksen S, Vernstrøm L, Sørensen SS, Funck KL, Poulsen PL, Laugesen E. Effects of semaglutide and empagliflozin on markers of endothelial function in persons with type 2 diabetes: A post hoc analysis of a randomized clinical trial. Journal of diabetes and its complications 2026.

Neuromolecular medicine · 2026 · PMID 42622904 · BioNex Evolve (PubMed-indexed)

This animal study tested semaglutide in mice with experimentally induced brain inflammation and cognitive impairment. Semaglutide improved cognitive performance, reduced nerve-cell damage, and restored changes involved in communication between nerve cells. These effects involved a sugar-related modification of the AKT protein and activation of the AKT-mTOR signaling pathway.

Citation: Liu Q, Chen L, Zhang M, Wang Z, Wang X, Dong Y, Wang K, Jiang C, Yin Y. Semaglutide Alleviates LPS-Induced Cognitive Disorder via O-GlcNAcylation of AKT-mTOR Signaling Pathway Components. Neuromolecular medicine 2026.

Diabetes, obesity & metabolism · 2026 · PMID 42420793 · BioNex Evolve (PubMed-indexed)

This observational study reviewed semaglutide use for weight management in adults with overweight or obesity at a Danish primary care practice. Treatment interruptions and permanent discontinuation were common. Among people who continued treatment and had follow-up weight measurements, substantial average weight loss was observed.

Citation: Skandov MD, Christensen KM, Dalin DA, Unkerskov J, Brønden A, Lund M, Christensen MB, Karstoft K. Real-World Use of Semaglutide for Weight Management: Dose Titration, Discontinuation Patterns and Weight Changes. Diabetes, obesity & metabolism 2026.

JAMA psychiatry · 2026 · PMID 42054055 · BioNex Evolve (PubMed-indexed)

This secondary analysis of a randomized human trial examined semaglutide’s effects on motivation in adults with major depressive disorder and overweight or obesity. Participants receiving semaglutide showed greater willingness to exert physical effort for higher expected rewards. Modeling suggested this reflected a reduced perceived cost of effort, rather than a change in sensitivity to reward probability.

Citation: Gill H, Badulescu S, Shah H, Brudner RM, Phan L, Di Vincenzo JD, Tabassum A, Thanarajah SE, Llach CD, Rosenblat JD, McIntyre RS, Mansur RB. Semaglutide and Effort-Based Decision-Making in Major Depressive Disorder: A Randomized Clinical Trial. JAMA psychiatry 2026.

European journal of pharmacology · 2026 · PMID 42070764 · BioNex Evolve (PubMed-indexed)

This review examined semaglutide's cardiovascular effects, drawing on clinical evidence in patients and research into biological mechanisms. It highlighted promising cardiovascular benefits and mechanisms involving improved insulin resistance, reduced inflammation, and effects against artery plaque buildup. Digestive tolerability remained a concern, and potential loss of lean body mass required further validation.

Citation: Zhang J, Gao G, He M, Sun T. Insights into semaglutide cardiovascular research: Mechanisms, trials, and frontiers. European journal of pharmacology 2026.

AIDS (London, England) · 2026 · PMID 42084141 · BioNex Evolve (PubMed-indexed)

This secondary analysis of a human trial without a comparison group examined blood markers in adults with HIV and metabolic fatty liver disease who lost weight with semaglutide. Cardiovascular-risk-related fat particles and inflammation markers decreased. These reductions did not correlate with the extent of changes in weight, liver fat, or insulin resistance, suggesting an independent mechanism.

Citation: Lake JE, Kitch DW, Kantor A, Alonso C, Belaunzaran-Zamudio PF, Kulik GL, Hyatt AN, Fichtenbaum CJ, Brown TT, Landay A, Sattler F, Erlandson KM. Semaglutide improves markers of cardiovascular risk in people with HIV. AIDS (London, England) 2026.

Expert review of endocrinology & metabolism · 2026 · PMID 42552573 · BioNex Evolve (PubMed-indexed)

This review examined resmetirom and semaglutide in people with metabolic-associated steatohepatitis, a fatty liver disease involving inflammation, and liver scarring. Both drugs resolved the inflammatory liver disease and improved scarring in a significant proportion of patients, although digestive side effects can occur. Long-term health outcomes, treatment duration, and ways to select and monitor patients remain unresolved.

Citation: Adinolfi LE, Marrone A, Izzi A, Craxi A. Resmetirom and semaglutide: next-generation therapies for metabolic-associated steatohepatitis. Opportunities, challenges and issues. Expert review of endocrinology & metabolism 2026.

ClinicalTrials.gov · 2026 · NCT07617155 · ClinicalTrials.gov

This registered human trial will test whether adding a GLP-1 receptor agonist to standard care reduces repeat episodes of acute pancreatitis caused by high blood triglycerides in adults with a previous episode. It will also assess metabolic outcomes and safety. Recruitment has not started, and no results are reported.

Population / model

Hypertriglyceridemia Induced Acute Pancreatitis; Recurrent Acute Pancreatitis; Pancreatitis Relapsing; Hypertriglyceridemia

Citation: Peking Union Medical College Hospital. Effects of GLP-1 Agonists on Prevention of HTG-Induced Acute Pancreatitis Recurrence: Protocol for a Randomized Clinical Trial. ClinicalTrials.gov 2026.

Lancet (London, England) · 2026 · PMID 41765029 · PubMed

This open-label randomized trial compared oral orforglipron with oral semaglutide in adults whose type 2 diabetes was inadequately controlled with metformin. Orforglipron produced greater improvements in long-term blood sugar across the studied comparisons. Digestive side effects were more frequent with orforglipron and were mostly mild to moderate.

Citation: Rosenstock J, Yabe D, Cox D, Li J, Denning M, Wu WS, Liu R, Zhao Y. Efficacy and safety of once-daily oral orforglipron compared with oral semaglutide in adults with type 2 diabetes (ACHIEVE-3): a multinational, multicentre, non-inferiority, open-label, randomised, phase 3 trial.. Lancet (London, England) 2026.

ClinicalTrials.gov · 2026 · NCT07628985 · ClinicalTrials.gov

This registered randomized trial will compare bofanglutide with semaglutide in Latin American adults whose type 2 diabetes is inadequately controlled with metformin alone. It will assess blood sugar control, safety, and other health outcomes. Recruitment has not yet started, and no results are reported.

Population / model

Type 2 Diabetes Mellitus (T2DM)

Citation: Carnot Laboratories. BALANCE-DM2: A Multiregional, Randomized, Multicenter, Active-Controlled Confirmatory Phase III Study to Evaluate the Efficacy and Safety of Bofanglutide (GZR18) in Latin American Adults With Type 2 Diabetes Mellitus. ClinicalTrials.gov 2026.

ClinicalTrials.gov · 2026 · NCT07401992 · ClinicalTrials.gov

This recruiting randomized trial will compare oral semaglutide with placebo alongside topical treatment in people with plaque psoriasis and overweight, obesity, and/or type 2 diabetes. It will assess psoriasis severity, quality of life, and inflammation; no results are reported.

Population / model

Psoriasis (PsO); Obesity & Overweight; Diabetes Mellitus - Type 2

Citation: Hospital Universitario Dr. Jose E. Gonzalez. Effects of Semaglutide on Clinical Outcomes and Metabolic Inflammation in Psoriasis: A Randomized, Triple-Blind, Placebo-Controlled Clinical Trial. ClinicalTrials.gov 2026.

ClinicalTrials.gov · 2026 · NCT07592546 · ClinicalTrials.gov

This registered human trial will examine whether excess body fat is associated with brain abnormalities on MRI and whether semaglutide-associated weight loss changes brain health in otherwise healthy middle-aged adults. It has not yet begun recruiting, and no results are reported.

Population / model

Class I/II Obesity

Citation: Alain Dagher. Translational Health Research Into Vascular and Neurocognitive Effects of Weight Loss. ClinicalTrials.gov 2026.

The Lancet · 2025 · PMID 40169145 · BioNex Evolve (PubMed-indexed)

This randomized human trial compared semaglutide with placebo in adults with type 2 diabetes and peripheral artery disease causing walking symptoms. Semaglutide significantly increased maximum treadmill walking distance compared with placebo. Some serious adverse events were considered possibly or probably treatment-related, but there were no treatment-related deaths.

Citation: Bonaca MP, Catarig AM, Houlind K, Ludvik B, Nordanstig J, Ramesh CK. Semaglutide and walking capacity in people with symptomatic peripheral artery disease and type 2 diabetes (STRIDE): a phase 3b, double-blind, randomised, placebo-controlled trial.. The Lancet 2025.

ClinicalTrials.gov · 2025 · NCT07064486 · ClinicalTrials.gov

This human trial in Indonesia compares the effectiveness and safety of BGM0504 with semaglutide, each added to metformin, in people with type 2 diabetes. It is recruiting participants, and no results are reported.

Population / model

Type 2 Diabetes (T2DM)

Citation: BrightGene Bio-Medical Technology Co., Ltd.. A Phase 3, Randomized, Open Label Trial Comparing Efficacy and Safety of BGM0504 Versus Semaglutide Once Weekly as Add-on Therapy to Metformin in Patients With Type 2 Diabetes. ClinicalTrials.gov 2025.

The New England journal of medicine · 2025 · PMID 40934115 · PubMed

This randomized human trial compared oral semaglutide with placebo, alongside lifestyle interventions, in adults with overweight or obesity who did not have diabetes. Semaglutide produced greater average weight loss and improved self-reported physical function compared with placebo. Gastrointestinal side effects were more common with semaglutide.

Citation: Wharton S, Lingvay I, Bogdanski P, Duque do Vale R, Jacob S, Karlsson T, Shaji C, Rubino D, Garvey WT. Oral Semaglutide at a Dose of 25 mg in Adults with Overweight or Obesity.. The New England journal of medicine 2025.

Circulation · 2025 · PMID 40156843 · PubMed

This analysis of a randomized trial examined oral semaglutide in people with type 2 diabetes and cardiovascular disease, chronic kidney disease, or both, according to SGLT2 inhibitor use. Semaglutide reduced major cardiovascular events, with no evidence that its effects differed by SGLT2 inhibitor use. Adverse-event profiles were similar, and the combination appeared safe.

Citation: Marx N, Deanfield JE, Mann JFE, Arechavaleta R, Bain SC, Bajaj HS, Bayer Tanggaard K, Birkenfeld AL, Buse JB, Davicevic-Elez Z, Desouza C, Emerson SS et al.. Oral Semaglutide and Cardiovascular Outcomes in People With Type 2 Diabetes, According to SGLT2i Use: Prespecified Analyses of the SOUL Randomized Trial.. Circulation 2025.

The New England journal of medicine · 2025 · PMID 40162642 · PubMed

This randomized trial compared oral semaglutide with placebo alongside standard care in adults with type 2 diabetes and cardiovascular disease, chronic kidney disease, or both. Semaglutide was associated with a significantly lower risk of major cardiovascular events without an increase in serious adverse events. Confirmatory secondary outcomes, including major kidney disease events, did not differ significantly.

Citation: McGuire DK, Marx N, Mulvagh SL, Deanfield JE, Inzucchi SE, Pop-Busui R, Mann JFE, Emerson SS, Poulter NR, Engelmann MDM, Ripa MS, Hovingh GK et al.. Oral Semaglutide and Cardiovascular Outcomes in High-Risk Type 2 Diabetes.. The New England journal of medicine 2025.

The Journal of clinical endocrinology and metabolism · 2025 · PMID 40489581 · PubMed

This systematic review and meta-analysis examined randomized trials of GLP-1-based therapies in people with metabolic dysfunction-associated fatty liver disease or its inflammatory form. These therapies reduced liver fat and improved liver-cell swelling, inflammation, liver enzymes, and liver stiffness. Improvement in liver scarring was not statistically significant.

Citation: Wang Y, Zhou Y, Wang Z, Ni Y, Prud'homme GJ, Wang Q. Efficacy of GLP-1-based Therapies on Metabolic Dysfunction-associated Steatotic Liver Disease and Metabolic Dysfunction-associated Steatohepatitis: A Systematic Review and Meta-analysis.. The Journal of clinical endocrinology and metabolism 2025.

JAMA psychiatry · 2025 · PMID 40900607 · PubMed

This randomized trial compared semaglutide with placebo in antipsychotic-treated adults with schizophrenia, prediabetes, and overweight or obesity. Semaglutide lowered blood sugar and body weight and improved physical quality of life, without significant effects on schizophrenia symptoms or mental quality of life. Digestive symptoms were more frequent, but serious adverse effects did not differ between groups.

Citation: Ganeshalingam AA, Uhrenholt N, Arnfred S, Gæde P, Düring S, Stenager EN, Bünger N, Pedersen AK, Bilenberg N, Frystyk J. Semaglutide Treatment of Antipsychotic-Treated Patients With Schizophrenia, Prediabetes, and Obesity: The HISTORI Randomized Clinical Trial.. JAMA psychiatry 2025.

ClinicalTrials.gov · 2025 · NCT06983171 · ClinicalTrials.gov

This ongoing human study evaluates semaglutide prescribed in routine care for people with metabolic dysfunction-associated fatty liver disease across different stages of liver scarring. The study is active but no longer recruiting, and no results are reported.

Population / model

MAFLD

Citation: Center of target therapy. Real-World Clinical Practice Study on the Effectiveness of Semaglutide Over 154 Weeks in Patients With Metabolic Dysfunction-Associated Fatty Liver Disease. ClinicalTrials.gov 2025.

ClinicalTrials.gov · 2025 · NCT06897475 · ClinicalTrials.gov

This recruiting clinical trial compares LY3457263 with placebo in people with type 2 diabetes whose blood sugar remains above target while receiving semaglutide or tirzepatide. It will measure changes in HbA1c, a marker of longer-term blood sugar levels; no results are reported.

Population / model

Type 2 Diabetes

Citation: Eli Lilly and Company. A Parallel-Group Treatment, Phase 2, Double-Blind Study of Once-Weekly Subcutaneous LY3457263 Compared to Placebo in Participants With Type 2 Diabetes Mellitus on a Stable Dose of Semaglutide or Tirzepatide Who Failed to Achieve HbA1c Goal. ClinicalTrials.gov 2025.

ClinicalTrials.gov · 2025 · NCT06989203 · ClinicalTrials.gov

This recruiting human trial is investigating whether adding dietary protein supplementation to semaglutide and a calorie-restricted diet affects weight loss, metabolism, muscle loss, and weight regain. It includes people with overweight or obesity and a normal-weight comparison group. The study is ongoing, and no results are provided.

Population / model

Obesity; Weight Loss; Protein Supplementation

Citation: Chinese Academy of Sciences. An Intervention Study Investigating Effect of Dietary Protein Supplementation on Body Weight and Metabolic Homeostasis. ClinicalTrials.gov 2025.

ClinicalTrials.gov · 2025 · NCT07819227 · ClinicalTrials.gov

This registered human trial compared finerenone and semaglutide in people with chronic kidney disease to identify which treatment best reduced protein leakage into urine for each individual. It also planned to assess combined treatment and home monitoring. The trial is listed as completed, but the supplied abstract reports no results.

Population / model

Chronic Kidney Disease

Citation: University Medical Center Groningen. Optimization of Albuminuria Lowering Therapies to Individual Patients With CKD Using FINErenone and SEmaglutide. ClinicalTrials.gov 2025.

ClinicalTrials.gov · 2025 · NCT07011667 · ClinicalTrials.gov

This registered human trial is studying whether CagriSema, a combination of cagrilintide and semaglutide, helps people with obesity lose weight and maintain that loss. It includes a randomized comparison with placebo followed by an extension study. The trial is ongoing and no longer recruiting, and no results are provided.

Population / model

Obesity

Citation: Novo Nordisk A/S. Efficacy and Safety of Cagrilintide s.c. in Combination With Semaglutide s.c. (CagriSema s.c.) Once Weekly for Weight Management and Long-term Weight Maintenance in Participants With Obesity. ClinicalTrials.gov 2025.

Diabetes Care · 2024 · PMID 38843460 · BioNex Evolve (PubMed-indexed)

This review examined effectiveness and safety evidence for GLP-1-based medicines in people with type 2 diabetes and obesity. It highlighted evidence of effectiveness and heart and kidney benefits in selected patient groups, alongside safety considerations. Trials exploring other conditions were ongoing, and the abstract did not report their results.

Citation: Drucker DJ. Efficacy and Safety of GLP-1 Medicines for Type 2 Diabetes and Obesity.. Diabetes Care 2024.

Drug design, development and therapy · 2024 · PMID 38952487 · BioNex Evolve (PubMed-indexed)

This systematic review examined how oral and injected semaglutide are absorbed, distributed, and cleared in healthy people and people with medical conditions. Semaglutide showed predictable behavior and remained in the body for a long time, with limited drug interactions. Food and administration conditions affected oral absorption, while body weight may affect exposure.

Citation: Yang XD, Yang YY. Clinical Pharmacokinetics of Semaglutide: A Systematic Review.. Drug design, development and therapy 2024.

JAMA ophthalmology · 2024 · PMID 38958939 · BioNex Evolve (PubMed-indexed)

This observational study examined patient records from a specialist eye center for a link between semaglutide prescriptions and NAION, an optic nerve condition involving reduced blood flow. Semaglutide prescriptions were associated with higher NAION risk in patients with type 2 diabetes or overweight or obesity. The study could not establish causation.

Citation: Hathaway JT, Shah MP, Hathaway DB, Zekavat SM, Krasniqi D, Gittinger JW, Cestari D, Mallery R, Abbasi B, Bouffard M, Chwalisz BK, Estrela T. Risk of Nonarteritic Anterior Ischemic Optic Neuropathy in Patients Prescribed Semaglutide.. JAMA ophthalmology 2024.

Expert opinion on pharmacotherapy · 2024 · PMID 38629387 · BioNex Evolve (PubMed-indexed)

This systematic review examined semaglutide's effects on lean body mass in adults with overweight or obesity, with or without type 2 diabetes. Weight loss mainly reflected fat loss, but lean mass remained stable in some studies and declined notably in others, particularly larger trials. The proportion of body weight made up of lean mass nevertheless increased.

Citation: Bikou A, Dermiki-Gkana F, Penteris M, Constantinides TK, Kontogiorgis C. A systematic review of the effect of semaglutide on lean mass: insights from clinical trials.. Expert opinion on pharmacotherapy 2024.

Diabetologia · 2024 · PMID 38613667 · BioNex Evolve (PubMed-indexed)

This systematic review and network meta-analysis compared injected tirzepatide and semaglutide using randomized trials in adults with type 2 diabetes. Overall, tirzepatide had a more pronounced effect on blood sugar and weight reduction, although blood-sugar results varied across comparisons. Both drugs increased digestive adverse events compared with placebo, but neither increased serious adverse events or severe low blood sugar.

Citation: Karagiannis T, Malandris K, Avgerinos I, Stamati A, Kakotrichi P, Liakos A, Vasilakou D, Kakaletsis N, Tsapas A, Bekiari E. Subcutaneously administered tirzepatide vs semaglutide for adults with type 2 diabetes: a systematic review and network meta-analysis of randomised controlled trials.. Diabetologia 2024.

Redox biology · 2024 · PMID 38574433 · BioNex Evolve (PubMed-indexed)

This animal and lab study examined semaglutide in mice and cell experiments modeling heart damage caused by the chemotherapy drug doxorubicin. Semaglutide improved heart function and the function of mitochondria, the cells' energy-producing structures, by reducing mitochondrial BNIP3 through the PI3K/AKT signaling pathway. Increasing BNIP3 specifically in the heart prevented the improvement in heart function.

Citation: Li X, Luo W, Tang Y, Wu J, Zhang J, Chen S, Zhou L, Tao Y, Tang Y, Wang F, Huang Y, Jose PA. Semaglutide attenuates doxorubicin-induced cardiotoxicity by ameliorating BNIP3-Mediated mitochondrial dysfunction.. Redox biology 2024.

Current issues in molecular biology · 2024 · PMID 39728000 · BioNex Evolve (PubMed-indexed)

This review explores how semaglutide may affect metabolism, inflammation, muscle, and fat tissue, drawing on human trials and animal research. Clinical findings indicate cardiovascular and metabolic benefits, while proposed mechanisms include effects on inflammation and cellular maintenance. Most evidence for these mechanisms comes from rodent studies and remains unconfirmed in humans.

Citation: Papakonstantinou I, Tsioufis K, Katsi V. Spotlight on the Mechanism of Action of Semaglutide.. Current issues in molecular biology 2024.

ClinicalTrials.gov · 2024 · NCT05746039 · ClinicalTrials.gov

This human pilot trial is testing whether semaglutide for weight loss is feasible and tolerable in patients with advanced lung disease. It will also assess lung function, physical function, body composition, and side effects. The trial is recruiting, and no results are reported.

Population / model

Obesity; Interstitial Lung Disease; Chronic Obstructive Pulmonary Disease; Sarcoidosis, Pulmonary; Pulmonary Hypertension

Citation: University of Pennsylvania. Feasibility of Semaglutide Therapy for Weight Loss in Advanced Lung Disease: A Pilot Study. ClinicalTrials.gov 2024.

The lancet. Diabetes & endocrinology · 2024 · PMID 38330988 · PubMed

This randomized trial compared semaglutide with placebo in predominantly East Asian adults with overweight or obesity, with or without type 2 diabetes. Alongside diet and physical activity support, semaglutide produced greater weight loss than placebo. Digestive side effects were more common with semaglutide.

Citation: Mu Y, Bao X, Eliaschewitz FG, Hansen MR, Kim BT, Koroleva A, Ma RCW, Yang T, Zu N, Liu M. Efficacy and safety of once weekly semaglutide 2·4 mg for weight management in a predominantly east Asian population with overweight or obesity (STEP 7): a double-blind, multicentre, randomised controlled trial.. The lancet. Diabetes & endocrinology 2024.

The New England journal of medicine · 2024 · PMID 39476339 · PubMed

This randomized trial compared semaglutide with placebo in people with obesity and painful knee osteoarthritis, alongside diet and activity counseling. Semaglutide produced greater reductions in body weight and knee pain, and greater improvement in physical functioning. Serious adverse events were similar, but more participants stopped semaglutide because of adverse events, most commonly digestive problems.

Citation: Bliddal H, Bays H, Czernichow S, Uddén Hemmingsson J, Hjelmesæth J, Hoffmann Morville T, Koroleva A, Skov Neergaard J, Vélez Sánchez P, Wharton S, Wizert A, Kristensen LE. Once-Weekly Semaglutide in Persons with Obesity and Knee Osteoarthritis.. The New England journal of medicine 2024.

The American journal of cardiology · 2024 · PMID 38679221 · PubMed

This systematic review combined randomized trials examining long-term semaglutide use in people with overweight or obesity without diabetes. Compared with placebo, semaglutide was associated with substantial, sustained weight loss. Digestive side effects were more common, but most were temporary, mild to moderate, and did not require stopping treatment.

Citation: Moiz A, Levett JY, Filion KB, Peri K, Reynier P, Eisenberg MJ. Long-Term Efficacy and Safety of Once-Weekly Semaglutide for Weight Loss in Patients Without Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.. The American journal of cardiology 2024.

Current medical research and opinion · 2024 · PMID 39046272 · PubMed

This meta-analysis examined semaglutide’s safety across randomized human trials involving different patient populations and treatment durations. It identified nausea and vomiting as associated adverse events and reported no significant differences between semaglutide and comparator groups. The authors described the safety profile as appearing favorable but called for further long-term studies.

Citation: Rivera FB, Arias-Aguirre E, Aguirre Z, Ybañez MJC, Rubia JMM, Galang DJ, Lumbang GN, Ruyeras JMMJ, Magalong JV, Pine PL, Amigo JAC, Ansay MFM et al.. Evaluating the safety profile of semaglutide: an updated meta-analysis.. Current medical research and opinion 2024.

The New England journal of medicine · 2024 · PMID 38785209 · PubMed

This randomized trial compared semaglutide with placebo in people with type 2 diabetes and chronic kidney disease. Semaglutide reduced the risk of clinically important kidney outcomes and death from cardiovascular causes. It also slowed kidney-function decline and reduced major cardiovascular events and deaths from any cause.

Citation: Perkovic V, Tuttle KR, Rossing P, Mahaffey KW, Mann JFE, Bakris G, Baeres FMM, Idorn T, Bosch-Traberg H, Lausvig NL, Pratley R. Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes.. The New England journal of medicine 2024.

Lancet (London, England) · 2024 · PMID 39222642 · PubMed

This post-hoc pooled analysis of randomized trials compared semaglutide with placebo in people with heart failure and mildly reduced or preserved pumping function. Semaglutide reduced the combined risk of cardiovascular death or worsening heart failure, and worsening heart failure alone. Its effect on cardiovascular death alone was not statistically significant.

Citation: Kosiborod MN, Deanfield J, Pratley R, Borlaug BA, Butler J, Davies MJ, Emerson SS, Kahn SE, Kitzman DW, Lingvay I, Mahaffey KW, Petrie MC et al.. Semaglutide versus placebo in patients with heart failure and mildly reduced or preserved ejection fraction: a pooled analysis of the SELECT, FLOW, STEP-HFpEF, and STEP-HFpEF DM randomised trials.. Lancet (London, England) 2024.

ClinicalTrials.gov · 2024 · NCT06323174 · ClinicalTrials.gov

This randomized human trial compared combined cagrilintide and semaglutide, called CagriSema, with placebo in adults whose type 2 diabetes was inadequately controlled by diet and exercise. It aimed to assess effects on blood sugar and body weight. The record lists the trial as completed, but no results are provided.

Population / model

Type 2 Diabetes

Citation: Novo Nordisk A/S. Efficacy and Safety of Co-administered Cagrilintide and Semaglutide (CagriSema) s.c. in Doses 2.4 mg/2.4 mg and 1.0 mg/1.0 mg Once Weekly Versus Placebo in Participants With Type 2 Diabetes Inadequately Controlled on Diet and Exercise. ClinicalTrials.gov 2024.

ClinicalTrials.gov · 2023 · NCT06042153 · ClinicalTrials.gov

This ongoing human trial compares semaglutide with placebo for blood sugar control in people with type 2 diabetes receiving chronic dialysis. It is active but no longer recruiting, and no results are reported.

Population / model

Type 2 Diabetes; End Stage Renal Disease on Dialysis

Citation: University of Texas Southwestern Medical Center. Semaglutide for Dialysis-Treated Patients - a Glucose Time in Range Study- DIALYSIS-TIR Study. ClinicalTrials.gov 2023.

Lancet (London, England) · 2023 · PMID 37385278 · PubMed

This randomized trial compared oral semaglutide with placebo, alongside lifestyle support, in adults with overweight or obesity without type 2 diabetes. Oral semaglutide led to greater, clinically meaningful weight loss. Digestive side effects were more common with semaglutide and were mostly mild to moderate.

Citation: Knop FK, Aroda VR, do Vale RD, Holst-Hansen T, Laursen PN, Rosenstock J, Rubino DM, Garvey WT. Oral semaglutide 50 mg taken once per day in adults with overweight or obesity (OASIS 1): a randomised, double-blind, placebo-controlled, phase 3 trial.. Lancet (London, England) 2023.

The New England journal of medicine · 2023 · PMID 37622681 · PubMed

This randomized trial studied semaglutide in people with obesity and heart failure with preserved ejection fraction, where the heart’s pumping percentage remains preserved. Compared with placebo, semaglutide led to greater reductions in symptoms, physical limitations, and body weight, and greater improvements in exercise function. Serious adverse events were reported less often with semaglutide.

Citation: Kosiborod MN, Abildstrøm SZ, Borlaug BA, Butler J, Rasmussen S, Davies M, Hovingh GK, Kitzman DW, Lindegaard ML, Møller DV, Shah SJ, Treppendahl MB et al.. Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction and Obesity.. The New England journal of medicine 2023.

ClinicalTrials.gov · 2023 · NCT05586802 · ClinicalTrials.gov

This recruiting randomized human trial is studying whether changing sex hormone balance improves metabolic health and sperm production in men with Klinefelter syndrome. It also evaluates semaglutide-associated weight loss against standard testosterone replacement and the addition of hCG to aromatase inhibitors. No results are reported.

Population / model

Klinefelter Syndrome

Citation: Georgios Papadakis. Dissecting the Importance of Sex Steroids Balance for Metabolic and Reproductive Health in Men With Klinefelter Syndrome: a Randomized Controlled Study. ClinicalTrials.gov 2023.

ClinicalTrials.gov · 2023 · NCT05597202 · ClinicalTrials.gov

This registered human trial investigates how type 2 diabetes affects blood vessel inflammation and the makeup of blood-forming stem cells. It asks whether activating GLP-1 receptors can reverse these changes. Its status is unknown, and no results are reported.

Population / model

Type 2 Diabetes

Citation: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA). Does the Hematopoietic Stem Cell Govern Residual Inflammatory Cardiovascular Risk in Type 2 Diabetes. ClinicalTrials.gov 2023.

Diabetes, Obesity and Metabolism · 2022 · PMID 35441470 · BioNex Evolve (PubMed-indexed)

This human trial extension followed adults with overweight or obesity without diabetes after semaglutide or placebo and lifestyle support were stopped. Participants previously receiving semaglutide regained much of their lost weight, and most improvements in heart and metabolic risk markers moved back toward baseline. The follow-up analyses were exploratory.

Citation: Wilding JPH, Batterham RL, Davies M, Van Gaal LF, Kandler K, Konakli K. Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension.. Diabetes, Obesity and Metabolism 2022.

Journal of the ASEAN Federation of Endocrine Societies · 2022 · PMID 36578889 · BioNex Evolve (PubMed-indexed)

This systematic review and meta-analysis combined randomized human trials of injected semaglutide in people with obesity without diabetes. Semaglutide produced greater weight loss than placebo. Digestive side effects, stopping treatment because of side effects, and serious adverse events were more likely with semaglutide.

Citation: Tan HC, Dampil OA, Marquez MM. Efficacy and Safety of Semaglutide for Weight Loss in Obesity Without Diabetes: A Systematic Review and Meta-Analysis.. Journal of the ASEAN Federation of Endocrine Societies 2022.

Journal of investigative medicine : the official publication of the American Federation for Clinical Research · 2022 · PMID 34706925 · BioNex Evolve (PubMed-indexed)

This review summarized human clinical trial programs studying oral or injected semaglutide in people with type 2 diabetes or obesity. The reviewed programs found greater weight reduction with semaglutide than with placebo and other diabetes medicines.

Citation: Singh G, Krauthamer M, Bjalme-Evans M. Wegovy (semaglutide): a new weight loss drug for chronic weight management.. Journal of investigative medicine : the official publication of the American Federation for Clinical Research 2022.

The lancet. Diabetes & endocrinology · 2022 · PMID 35131037 · BioNex Evolve (PubMed-indexed)

This randomized trial compared semaglutide with placebo in East Asian adults with overweight or obesity, with or without type 2 diabetes. Semaglutide produced greater average weight loss, and more participants reached the study's weight-loss target than with placebo.

Citation: Kadowaki T, Isendahl J, Khalid U, Lee SY, Nishida T, Ogawa W, Tobe K, Yamauchi T, Lim S. Semaglutide once a week in adults with overweight or obesity, with or without type 2 diabetes in an east Asian population (STEP 6): a randomised, double-blind, double-dummy, placebo-controlled, phase 3a trial.. The lancet. Diabetes & endocrinology 2022.

ClinicalTrials.gov · 2022 · NCT05193578 · ClinicalTrials.gov

This completed human trial investigated whether semaglutide could prevent diabetes and metabolic syndrome in people with prediabetes, overweight, and schizophrenia who take antipsychotic medication. It also examined psychotic symptoms and quality of life, but the abstract reports no results.

Population / model

Schizophrenia; Prediabetic State

Citation: Jan Frystyk. Home-based Intervention With Semaglutide Treatment Of Neuroleptica-Related Prediabetes. ClinicalTrials.gov 2022.

ClinicalTrials.gov · 2022 · NCT05443191 · ClinicalTrials.gov

This completed human observational study examined oral semaglutide use in routine care among adults with type 2 diabetes in Finland. It aimed to assess blood sugar lowering and collect questionnaire information about tablet use, but the abstract reports no results.

Population / model

Diabetes Mellitus, Type 2

Citation: Novo Nordisk A/S. A Multi-centre, Prospective, Non-interventional Single-arm Study Investigating Clinical Parameters Associated With the Use of Once-daily Oral Semaglutide in a Real-world Adult Population With Type 2 Diabetes in Finland. ClinicalTrials.gov 2022.

The New England journal of medicine · 2022 · PMID 36322838 · PubMed

This randomized human trial compared injected semaglutide with placebo, both alongside lifestyle intervention, in adolescents who almost all had obesity. Semaglutide led to greater reductions in body mass index and weight, with greater improvements in several heart and metabolic risk markers. Gastrointestinal side effects were more common with semaglutide, and gallstones occurred only in that group.

Citation: Weghuber D, Barrett T, Barrientos-Pérez M, Gies I, Hesse D, Jeppesen OK, Kelly AS, Mastrandrea LD, Sørrig R, Arslanian S. Once-Weekly Semaglutide in Adolescents with Obesity.. The New England journal of medicine 2022.

Nature medicine · 2022 · PMID 36216945 · PubMed

This randomized trial compared semaglutide with placebo, both alongside behavioral support, in adults with overweight and a weight-related condition or obesity, without diabetes. Semaglutide led to substantial, sustained weight loss over two years. Digestive side effects were more common with semaglutide and were mostly mild to moderate.

Citation: Garvey WT, Batterham RL, Bhatta M, Buscemi S, Christensen LN, Frias JP, Jódar E, Kandler K, Rigas G, Wadden TA, Wharton S. Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial.. Nature medicine 2022.

ClinicalTrials.gov · 2022 · NCT04938388 · ClinicalTrials.gov

This randomized human trial was designed to compare oral semaglutide with placebo in Hispanic/Latino adults with type 2 diabetes receiving enhanced lifestyle care, including fresh vegetables. Researchers planned to assess blood sugar, body measurements, and other health outcomes. The record lists the trial as terminated, and no results are provided.

Population / model

Diabetes Mellitus, Type 2; Glucose Metabolism Disorders (Including Diabetes Mellitus)

Citation: Sansum Diabetes Research Institute. Comparison of Oral Semaglutide With Matched Oral Semaglutide Placebo as an Early Treatment for Latino Adults With Type 2 Diabetes Receiving Enhanced Lifestyle Care. ClinicalTrials.gov 2022.

The Lancet · 2021 · PMID 33667417 · BioNex Evolve (PubMed-indexed)

This randomized human trial studied semaglutide for weight management in adults with overweight or obesity and type 2 diabetes, alongside a lifestyle intervention. Semaglutide produced a significantly greater, clinically meaningful decrease in body weight than placebo. Adverse events were more frequent with semaglutide, including digestive symptoms that were mostly mild to moderate.

Citation: Davies M, Færch L, Jeppesen OK, Pakseresht A, Pedersen SD, Perreault L. Semaglutide 2.4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial.. The Lancet 2021.

JAMA · 2021 · PMID 33755728 · BioNex Evolve (PubMed-indexed)

This randomized human trial compared continuing semaglutide with switching to placebo in adults with overweight or obesity without diabetes who completed an initial semaglutide period. Continuing semaglutide led to further weight loss, while switching to placebo led to weight regain; both groups received lifestyle support. Digestive side effects were more common with continued semaglutide.

Citation: Rubino D, Abrahamsson N, Davies M, Hesse D, Greenway FL, Jensen C. Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity: The STEP 4 Randomized Clinical Trial.. JAMA 2021.

Frontiers in endocrinology · 2021 · PMID 34305810 · BioNex Evolve (PubMed-indexed)

This review examined human safety evidence for injected and oral semaglutide, mainly in people with type 2 diabetes. It concluded that semaglutide mostly causes mild-to-moderate, temporary digestive side effects and increases gallstone risk, while having an overall favorable balance of benefits and risks. Pancreatic and thyroid cancer risks remained uncertain because these conditions were rare.

Citation: Smits MM, Van Raalte DH. Safety of Semaglutide.. Frontiers in endocrinology 2021.

ClinicalTrials.gov · 2021 · NCT04572165 · ClinicalTrials.gov

This observational human study used Nordic health registries to compare pancreatic cancer risk in people with type 2 diabetes starting semaglutide versus other diabetes medicines. It is marked completed, but the supplied abstract describes only the study methods and provides no findings about cancer risk.

Population / model

Diabetes Mellitus, Type 2

Citation: Novo Nordisk A/S. Epidemiological Assessment of the Risk for Pancreatic Cancer Associated With the Use of Semaglutide in Patients With Type 2 Diabetes - A Cohort Study Based on Nordic Registry Data. ClinicalTrials.gov 2021.

The New England journal of medicine · 2021 · PMID 34170647 · PubMed

This randomized, open-label human trial compared tirzepatide with semaglutide in patients with type 2 diabetes. Tirzepatide produced greater reductions in glycated hemoglobin, a measure of long-term blood sugar, and body weight. Gastrointestinal side effects were most common and generally mild to moderate in both groups; serious adverse events were reported more often with tirzepatide.

Citation: Frías JP, Davies MJ, Rosenstock J, Pérez Manghi FC, Fernández Landó L, Bergman BK, Liu B, Cui X, Brown K. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes.. The New England journal of medicine 2021.

Diabetes, obesity & metabolism · 2021 · PMID 33269530 · PubMed

This randomized trial studied semaglutide’s effects on appetite, eating, and stomach emptying in adults with obesity. Compared with placebo, semaglutide reduced hunger, food cravings, food intake, and body weight, while improving control of eating. An indirect test found no evidence of delayed stomach emptying at the end of the study.

Citation: Friedrichsen M, Breitschaft A, Tadayon S, Wizert A, Skovgaard D. The effect of semaglutide 2.4 mg once weekly on energy intake, appetite, control of eating, and gastric emptying in adults with obesity.. Diabetes, obesity & metabolism 2021.

The New England journal of medicine · 2021 · PMID 33567185 · PubMed

This randomized trial compared semaglutide with placebo, both alongside lifestyle support, in adults with overweight or obesity without diabetes. Semaglutide was associated with sustained, clinically relevant weight loss and greater improvements in physical functioning and heart and metabolic risk factors. Nausea and diarrhea were common, and more participants stopped semaglutide because of digestive side effects.

Citation: Wilding JPH, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I, McGowan BM, Rosenstock J, Tran MTD, Wadden TA, Wharton S, Yokote K et al.. Once-Weekly Semaglutide in Adults with Overweight or Obesity.. The New England journal of medicine 2021.

The lancet. Diabetes & endocrinology · 2021 · PMID 34293304 · PubMed

This randomized trial compared semaglutide regimens in adults whose type 2 diabetes was inadequately controlled with metformin, with or without a sulfonylurea. Blood sugar improvement was greater with one regimen, while the statistical significance of the weight-loss difference depended on the analysis. Digestive problems were the most common adverse events, and serious adverse events were similar between groups.

Citation: Frías JP, Auerbach P, Bajaj HS, Fukushima Y, Lingvay I, Macura S, Søndergaard AL, Tankova TI, Tentolouris N, Buse JB. Efficacy and safety of once-weekly semaglutide 2·0 mg versus 1·0 mg in patients with type 2 diabetes (SUSTAIN FORTE): a double-blind, randomised, phase 3B trial.. The lancet. Diabetes & endocrinology 2021.

JAMA · 2021 · PMID 33625476 · PubMed

This randomized trial compared semaglutide with placebo alongside intensive behavioral therapy and an initial low-calorie diet in adults with overweight or obesity without diabetes. Semaglutide produced significantly greater weight loss, but digestive side effects were more frequent. The authors noted that further research was needed to assess whether the findings would last.

Citation: Wadden TA, Bailey TS, Billings LK, Davies M, Frias JP, Koroleva A, Lingvay I, O'Neil PM, Rubino DM, Skovgaard D, Wallenstein SOR, Garvey WT. Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity: The STEP 3 Randomized Clinical Trial.. JAMA 2021.

ClinicalTrials.gov · 2021 · NCT04777409 · ClinicalTrials.gov

This completed randomized trial studied the effects and safety of oral semaglutide compared with placebo in people with early Alzheimer's disease. The record describes the study procedures but provides no results.

Population / model

Early Alzheimer´s Disease

Citation: Novo Nordisk A/S. A Randomised Double-blind Placebo-controlled Clinical Trial Investigating the Effect and Safety of Oral Semaglutide in Subjects With Early Alzheimer´s Disease (EVOKE Plus). ClinicalTrials.gov 2021.

JCI insight · 2020 · PMID 32213703 · BioNex Evolve (PubMed-indexed)

This animal study examined how semaglutide affects body weight and brain pathways in rodents. Semaglutide changed food preferences, reduced food intake, and caused weight loss without decreasing energy expenditure. The researchers suggested that these effects involve direct and indirect changes in brain pathways controlling eating, reward, and energy use.

Citation: Gabery S, Salinas CG, Paulsen SJ, Ahnfelt-Rønne J, Alanentalo T, Baquero AF, Buckley ST, Farkas E, Fekete C, Frederiksen KS, Helms HCC, Jeppesen JF. Semaglutide lowers body weight in rodents via distributed neural pathways.. JCI insight 2020.

Obesity (Silver Spring, Md.) · 2020 · PMID 32441473 · PubMed

This report describes the registered STEP randomized trials comparing semaglutide with placebo in adults with overweight or obesity, including people with and without type 2 diabetes. The trials assess weight loss, safety, and tolerability and were ongoing at the time of the report; no treatment results are presented.

Citation: Kushner RF, Calanna S, Davies M, Dicker D, Garvey WT, Goldman B, Lingvay I, Thomsen M, Wadden TA, Wharton S, Wilding JPH, Rubino D. Semaglutide 2.4 mg for the Treatment of Obesity: Key Elements of the STEP Trials 1 to 5.. Obesity (Silver Spring, Md.) 2020.

ClinicalTrials.gov · 2020 · NCT04287179 · ClinicalTrials.gov

This planned human trial aimed to compare semaglutide treatment schedules and evaluate a new injection pen in people with type 2 diabetes previously treated with similar medicines. The trial was withdrawn, and no results are reported.

Population / model

Diabetes Mellitus, Type 2

Citation: Novo Nordisk A/S. Effect and Safety of Two Different Dose-escalation Regimens for Once-weekly Semaglutide s.c. in Subjects With Type 2 Diabetes Mellitus Previously Treated With GLP-1 RAs. ClinicalTrials.gov 2020.

ClinicalTrials.gov · 2020 · NCT04560998 · ClinicalTrials.gov

This registered randomized human trial compared semaglutide with placebo to assess walking ability in people with type 2 diabetes and peripheral arterial disease. Walking distance was to be measured using treadmill tests. The trial is listed as completed, but the supplied abstract reports no results.

Population / model

Diabetes Mellitus, Type 2; Peripheral Arterial Disease

Citation: Novo Nordisk A/S. Effects of Semaglutide on Functional Capacity in Patients With Type 2 Diabetes and Peripheral Arterial Disease. ClinicalTrials.gov 2020.

ClinicalTrials.gov · 2020 · NCT04447859 · ClinicalTrials.gov

This registered randomized trial plans to compare slower versus standard semaglutide dose escalation in people with type 2 diabetes, focusing on digestive side effects. Its status is unknown, and no results are reported.

Population / model

Diabetes type2

Citation: Tel-Aviv Sourasky Medical Center. A Randomized Controlled Open Label Pilot Study Examining the Safety of a 16 Week Flexible Titration Regimen vs. Label-recommended 8-week Semaglutide Titration Regimen. ClinicalTrials.gov 2020.

ClinicalTrials.gov · 2019 · NCT04109508 · ClinicalTrials.gov

This completed human trial compared the body's uptake of semaglutide from an existing oral tablet formulation and a new formulation in healthy participants. The record describes the study design but provides no results.

Population / model

Healthy Volunteers; Type 2 Diabetes

Citation: Novo Nordisk A/S. A Comparative Bioavailability Trial of Steady State Semaglutide Exposure With the Current Formulation (Semaglutide) and a New Formulation (Semaglutide C) of Oral Semaglutide in Healthy Subjects. ClinicalTrials.gov 2019.

The lancet. Diabetes & endocrinology · 2018 · PMID 29397376 · BioNex Evolve (PubMed-indexed)

This randomized, open-label trial compared semaglutide with dulaglutide in adults whose type 2 diabetes was inadequately controlled with metformin. Semaglutide produced greater reductions in blood sugar and body weight in both comparisons studied. Digestive problems were the most frequently reported side effects.

Citation: Pratley RE, Aroda VR, Lingvay I, Lüdemann J, Andreassen C, Navarria A, Viljoen A. Semaglutide versus dulaglutide once weekly in patients with type 2 diabetes (SUSTAIN 7): a randomised, open-label, phase 3b trial.. The lancet. Diabetes & endocrinology 2018.

Diabetes, obesity & metabolism · 2018 · PMID 29756388 · PubMed

This systematic review combined randomized trials of semaglutide in people with type 2 diabetes. Injectable semaglutide improved long-term blood sugar more than placebo and several other diabetes medicines, and reduced body weight and systolic blood pressure. Digestive side effects increased, while findings on pancreatic inflammation and diabetes-related eye damage required further assessment.

Citation: Andreadis P, Karagiannis T, Malandris K, Avgerinos I, Liakos A, Manolopoulos A, Bekiari E, Matthews DR, Tsapas A. Semaglutide for type 2 diabetes mellitus: A systematic review and meta-analysis.. Diabetes, obesity & metabolism 2018.

The Lancet Diabetes & Endocrinology · 2017 · PMID 28110911 · BioNex Evolve (PubMed-indexed)

This randomized human trial compared semaglutide alone with placebo in adults with type 2 diabetes whose blood sugar was insufficiently controlled by diet and exercise. Semaglutide significantly reduced HbA1c, a measure of longer-term blood sugar, compared with placebo. Digestive adverse events such as nausea were the main reason for stopping treatment; the supplied abstract cuts off before the weight results.

Citation: Sorli C, Harashima SI, Tsoukas GM, Unger J, Karsbøl JD, Hansen T. Efficacy and safety of once-weekly semaglutide monotherapy versus placebo in patients with type 2 diabetes (SUSTAIN 1): a double-blind, randomised, placebo-controlled, parallel-group, multinational, multicentre phase 3a trial.. The Lancet Diabetes & Endocrinology 2017.

ClinicalTrials.gov · 2017 · NCT03061214 · ClinicalTrials.gov

This randomized human trial compared semaglutide with sitagliptin for blood sugar control in people with type 2 diabetes who continued taking metformin. The trial is marked completed, but the supplied abstract describes only its design and provides no results.

Population / model

Diabetes; Diabetes Mellitus, Type 2

Citation: Novo Nordisk A/S. Efficacy and Safety of Semaglutide Once-weekly Versus Sitagliptin Once-daily as add-on to Metformin in Subjects With Type 2 Diabetes. A 30-week Randomised, Double-blind, Double-dummy, Active-controlled, Parallel-group, Multi-centre and Multi-national Trial. ClinicalTrials.gov 2017.

The New England journal of medicine · 2016 · PMID 27633186 · PubMed

This randomized trial compared semaglutide with placebo in people with type 2 diabetes at high cardiovascular risk. Semaglutide significantly lowered the combined rate of cardiovascular death, nonfatal heart attack, or nonfatal stroke, while cardiovascular death alone was similar between groups. Kidney complications were less frequent, but diabetic eye complications and treatment discontinuation due mainly to digestive side effects were more frequent.

Citation: Marso SP, Bain SC, Consoli A, Eliaschewitz FG, Jódar E, Leiter LA, Lingvay I, Rosenstock J, Seufert J, Warren ML, Woo V, Hansen O et al.. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes.. The New England journal of medicine 2016.

ClinicalTrials.gov · 2016 · NCT02920385 · ClinicalTrials.gov

This completed registered trial in healthy people examined whether oral semaglutide changes the body's exposure to levothyroxine and whether taking other tablets alongside semaglutide changes semaglutide exposure. The supplied record describes the study aims but reports no results.

Population / model

Diabetes; Healthy

Citation: Novo Nordisk A/S. A Trial Investigating the Influence of Oral Semaglutide on the Pharmacokinetics of Levothyroxine and the Influence of Co-administered Tablets on the Pharmacokinetics of Semaglutide Administered Orally in Healthy Subjects. ClinicalTrials.gov 2016.

ClinicalTrials.gov · 2014 · NCT02172313 · ClinicalTrials.gov

This completed human trial investigated how food affects the body's exposure to oral semaglutide in healthy participants. The record describes the study aim but provides no results.

Population / model

Diabetes; Healthy

Citation: Novo Nordisk A/S. Effect of Food on the Pharmacokinetics of Oral Semaglutide in Healthy Subjects. ClinicalTrials.gov 2014.

ClinicalTrials.gov · 2014 · NCT02079870 · ClinicalTrials.gov

This randomized human trial compared semaglutide with placebo in people with obesity. It investigated food energy intake, appetite, blood sugar and fat metabolism after meals, and how quickly the stomach empties. The record lists the trial as completed, but no results are provided.

Population / model

Diabetes; Metabolism and Nutrition Disorder; Obesity

Citation: Novo Nordisk A/S. A Single-centre, Randomised, Double-blind Two-period Cross-over Trial Investigating the Effect of Semaglutide on Energy Intake, Appetite Sensations, Postprandial Glucose and Triglyceride Metabolism and Gastric Emptying in Obese Subjects Compared With Placebo. ClinicalTrials.gov 2014.

2006 · PMID 30000039 · BioNex Evolve (PubMed-indexed)

The title identifies semaglutide as the subject but does not specify a population or research question. The abstract was not available, so results are not summarized.

ISRCTN · ISRCTN11609964 · ISRCTN

The title describes a human feasibility study of introducing a low-energy formula diet programme for weight loss within a kidney transplant service. The abstract was not available, so results are not summarized.

Citation: University College London. INFILTRATE: ImplemeNtation of a Formula low energy diet programme for weight loss In a renaL TRansplAnT sErvice Study - Work package 3 Feasibility Study. ISRCTN .

ISRCTN · ISRCTN12382879 · ISRCTN

The title describes a randomized feasibility trial of using “Digital Clinicians” to teach people how to self-inject obesity medication. The abstract was not available, so results are not summarized.

Citation: University Hospital Galway. OBESITY medication self-injection education using “Digital Clinicians”: a feasibility randomised controlled trial. ISRCTN .

ISRCTN · ISRCTN13040627 · ISRCTN

The title concerns semaglutide use for elective weight loss in people without obesity and possible health benefits. The abstract was not available, so results are not summarized.

Citation: Sharon Giese, MD. Use of semaglutide for successful elective weight loss in a non-obese population and likely health benefits. ISRCTN .

ISRCTN · ISRCTN13721429 · ISRCTN

The title describes a randomized trial comparing the PROGROUP group-based behavioral weight-management program with usual care in adults receiving specialist NHS services for severe obesity. The abstract was not available, so results are not summarized.

Citation: University Hospitals Plymouth NHS Trust. A group-based behavioural intervention for weight management (PROGROUP) versus usual care in adults accessing NHS Tier 3 weight management services for treatment of severe obesity: a multi-centre, two-arm, individually randomised controlled, assessor-blinded, adaptive superiority trial with parallel process evaluation and health economic evaluation. ISRCTN .

ISRCTN · ISRCTN14945909 · ISRCTN

This randomized human trial compares nutritional ketosis, a dietary approach that shifts the body toward using fat for fuel, with the NHS Eatwell guide in people with bipolar depression. The abstract was not available, so results are not summarized.

Citation: University of Edinburgh and NHS Lothian. Evaluating nutritional ketosis versus NHS Eatwell guide for bipolar depression: single blind randomised controlled trial. ISRCTN .

ISRCTN · ISRCTN16072024 · ISRCTN

The title describes a randomized human trial comparing alginate plus lifestyle changes with a proton pump inhibitor (PPI) for mild to moderate acid reflux. The abstract was not available, so results are not summarized.

Citation: Reckitt Benckiser Health Limited ("Reckitt”). An unblinded, randomised, interventional cohort two-arm trial of alginate with lifestyle interventions versus PPI in the management of mild to moderate gastro-oesophageal reflux. ISRCTN .

ISRCTN · ISRCTN17589855 · ISRCTN

The title describes a controlled dietary study comparing how calorie restriction affects body composition, blood sugar regulation, energy balance, and fat metabolism in younger and older men and women with overweight or obesity, including a substudy of oestrogen hormone replacement therapy in postmenopausal women. The abstract was not available, so results are not summarized.

Citation: University of Aberdeen. Gender- and age-dependent effects of caloric restriction on body composition, glucose homeostasis, energy balance and adipose metabolism in overweight and obese adults: a controlled dietary intervention study comparing younger and older men and women, with an embedded sub-study examining the role of oestrogen hormone replacement therapy (HRT) in postmenopausal women (GendAge Study). ISRCTN .

ISRCTN · ISRCTN29694121 · ISRCTN

The title describes research on semaglutide as an added treatment to improve blood sugar control in children and young people with type 1 diabetes. The abstract was not available, so results are not summarized.

Citation: University of Birmingham. Semaglutide as an add-on treatment to optimise glycaemic control in children and young people with type 1 diabetes (Smile T1D). ISRCTN .

ISRCTN · ISRCTN33756948 · ISRCTN

The title describes a human study examining the separate contributions of weight loss and diet composition to blood sugar levels in people with type 2 diabetes. The abstract was not available, so results are not summarized.

Citation: University of Oxford. Disentangling the contribution of weight loss and diet composition on glycaemia in type 2 diabetes. ISRCTN .

ISRCTN · ISRCTN60358675 · ISRCTN

This exploratory human trial evaluates new oral semaglutide tablets designed to modify how the medicine is released, using imaging in healthy volunteers. The abstract was not available, so results are not summarized.

Citation: BDD Pharma Ltd. An exploratory pharmacoscintigraphic single centre, open-label, crossover study in healthy volunteers to evaluate novel oral modified release semaglutide tablets. ISRCTN .

ISRCTN · ISRCTN71283871 · ISRCTN

The title concerns semaglutide’s impact on amyloid positivity, meaning a positive finding for amyloid protein, but does not identify the study population. The abstract was not available, so results are not summarized.

Citation: Imperial College London. Impact of semaglutide in amyloid positivity. ISRCTN .

ISRCTN · ISRCTN76193287 · ISRCTN

ASCEND PLUS is a human study of cardiovascular events in people with diabetes. The abstract was not available, so results are not summarized.

Citation: University of Oxford. A Study of Cardiovascular Events iN Diabetes Plus (ASCEND PLUS). ISRCTN .

ISRCTN · ISRCTN76893830 · ISRCTN

This pilot human study examines the safety and feasibility of simplifying or stopping insulin in frail older adults with type 2 diabetes, using C-peptide to help clarify and personalize diabetes management. The abstract was not available, so results are not summarized.

Citation: University of Dundee. Safety and feasibility of insulin simplification or cessation in frail older adults with type 2 diabetes: a pilot study of CLASP (using C-peptide to clarify, simplify and personalise type 2 diabetes management in frail older adults). ISRCTN .

ClinicalTrials.gov · 2027 · NCT07622992 · ClinicalTrials.gov

This registered human study will compare tirzepatide, a ketogenic diet, and standard care before gastric bypass surgery in people with severe obesity. Researchers will assess weight loss after surgery, safety, and obesity-related health conditions. Recruitment has not yet begun, and no results are reported.

Population / model

Obesity (BMI > 35) and Diabetes Mellitus; Obesity (BMI > 35) and Dyslipemia; Obesity (BMI > 35) and High Blood Pressure

Citation: Mario Musella MD. Efficacy of Preoperative Tirzepatide, Ketogenic Diet, and Standard Care on 1-Year Weight Loss After One Anastomosis Gastric Bypass (OAGB). ClinicalTrials.gov 2027.

Diabetes, obesity & metabolism · 2026 · PMID 41491349 · BioNex Evolve (PubMed-indexed)

This observational study compared semaglutide and tirzepatide using US health insurance records for people with overweight or obesity and established artery disease, but without diabetes. Semaglutide was associated with a significantly lower risk of combined cardiovascular events and death than tirzepatide. The study was not randomized.

Citation: Wilson L, Zhao Z, Divino V, Bassan M, Hartaigh BÓ, Stensen S, Ozer K. Semaglutide and tirzepatide effects on cardiovascular outcomes in people with overweight or obesity in the real world (STEER).. Diabetes, obesity & metabolism 2026.

Endocrine · 2026 · PMID 42603240 · BioNex Evolve (PubMed-indexed)

This systematic review and meta-analysis examined blood pressure-related adverse events in randomized trials involving people with type 2 diabetes or obesity. Tirzepatide was associated with fewer high blood pressure events but more low blood pressure events. Semaglutide showed no statistically significant association with either type of event overall.

Citation: Chen QX, Zhou XY, Wu Q, Xie JJ, Xu Y, Teng FY, Guo M. Effect of tirzepatide and semaglutide on blood pressure: A systematic review and meta-analysis. Endocrine 2026.

Medicina (Kaunas, Lithuania) · 2026 · PMID 42654433 · BioNex Evolve (PubMed-indexed)

This systematic review examined whether the day of semaglutide or tirzepatide administration affects outcomes in adults with type 2 diabetes or obesity. No studies directly compared different weekdays for the injectable drugs, so current evidence does not support an optimal day. Suggestions that flexible schedules may help adherence and tolerability came mainly from indirect evidence and expert opinion.

Citation: La Vignera S, Condorelli RA. Is There a Better Day of the Week to Administer Semaglutide or Tirzepatide? A Systematic Literature Review. Medicina (Kaunas, Lithuania) 2026.

Clinical obesity · 2026 · PMID 42670242 · BioNex Evolve (PubMed-indexed)

This systematic review combined trials and observational studies comparing tirzepatide with semaglutide in adults with overweight or obesity. Tirzepatide was associated with greater weight loss and improved long-term blood sugar levels, but serious adverse events were more frequent. Overall side effects, digestive side effects, and treatment discontinuation due to adverse events did not differ significantly.

Citation: Paccola GP, de Oliveira RF, Mochetti MM, Razera FPM, Vecchi R, Montanher RCP. Comparative Efficacy of Tirzepatide Versus Semaglutide for Weight Loss in Adults With Overweight or Obesity: A Systematic Review and Meta-Analysis of Head-to-Head Studies. Clinical obesity 2026.

Therapeutic advances in endocrinology and metabolism · 2026 · PMID 42534427 · BioNex Evolve (PubMed-indexed)

This review examined tirzepatide's metabolic and cardiovascular effects in people with type 2 diabetes or obesity. It reported improvements in blood sugar, weight, blood pressure, blood fats, and inflammation, with promising symptom and function findings in obesity-related heart failure. The review states that effects on major cardiovascular events and long-term outcomes remain under investigation.

Citation: Alawad AO, Merghani TH, Fadelelmoula TE, Elamin NA, Satti S, Edris AA, Hakim A, El-Hindi RF, Alhaj-Ali AA, Ibrahim WE, Mustafa MA, Sirelkhatim MM, Ahmed HH, Yousif NO. Beyond glycemic control: clinical cardiovascular effects of tirzepatide-a narrative review. Therapeutic advances in endocrinology and metabolism 2026.

Diabetes research and clinical practice · 2026 · PMID 42442557 · BioNex Evolve (PubMed-indexed)

This systematic review pooled randomized trials of tirzepatide in adults with type 2 diabetes or overweight or obesity. Tirzepatide was associated with fewer major cardiovascular events considered together and fewer deaths from any cause. No association was found for individual cardiovascular event types or heart failure hospitalizations.

Citation: Spiazzi BF, Zingano CP, Colpani V, Gerchman F. Tirzepatide, cardiovascular outcomes and mortality in obesity and diabetes: a systematic review and meta-analysis. Diabetes research and clinical practice 2026.

BMJ (Clinical research ed.) · 2026 · PMID 42556854 · BioNex Evolve (PubMed-indexed)

This observational study compared tirzepatide with sitagliptin in adults with type 2 diabetes and established artery disease. Tirzepatide was associated with a lower combined risk of heart attack, stroke, or death, although ischemic stroke alone showed no meaningful difference. Hospital admissions for infections and infection-related deaths were also lower.

Citation: Krüger N, Schneeweiss S, Wang SV. Tirzepatide and the risk of atherosclerotic cardiovascular events: population based cohort study. BMJ (Clinical research ed.) 2026.

Frontiers in microbiology · 2026 · PMID 42499664 · BioNex Evolve (PubMed-indexed)

This review examined research on obesity, gut microbes, and tirzepatide rather than reporting a new experiment. Evidence suggests tirzepatide may be associated with changes in gut microbes, their products, intestinal barrier function, and inflammation. Whether these changes are direct drug effects or consequences of weight loss, dietary changes, or improved blood sugar control remains unclear.

Citation: Cadena-Ullauri S, Cadena Paredes AS, Guamán-Herrera L, Imbaquingo-Espinales J, Ruiz-Pozo VA, Tamayo-Trujillo R, Guevara-Ramírez P, Paz-Cruz E, Zambrano AK. Tirzepatide and the gut microbiota-obesity axis: metabolic mechanisms and therapeutic perspectives. Frontiers in microbiology 2026.

Clinical nutrition ESPEN · 2026 · PMID 42542297 · BioNex Evolve (PubMed-indexed)

This prospective observational study followed adults with obesity or overweight and weight-related health problems who received tirzepatide in routine care. Tirzepatide use was associated with weight loss, improved blood sugar and blood fat measures, and better health-related quality of life. The study reported a favorable tolerability profile.

Citation: Pérez-Pevida B, Santana Santana M, Liaño Arriola C, Maldonado A, Clérigo B, Ruiz C, Higueruela C, Ballesteros-Pomar MD, Bretón Lesmes I, Moreira Rodríguez M. Real-world evaluation of the effectiveness and safety of tirzepatide in patients with obesity: A prospective study. Clinical nutrition ESPEN 2026.

Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine · 2026 · PMID 42675225 · BioNex Evolve (PubMed-indexed)

This exploratory analysis of human trial data examined tirzepatide in adults with obesity and moderate-to-severe obstructive sleep apnea. Tirzepatide was associated with improvements in breathing interruptions, sleep-related oxygen deprivation, body weight, and systolic blood pressure across baseline subgroups, generally exceeding placebo. These after-the-fact analyses were intended to generate hypotheses.

Citation: Falcon B, Xie CC, Redline S, Grunstein R, Turnbull CD, Rapoport DM, Wang H, Chakladar S, Dimitriadis GK, Lau E, Bednarik J, Liao B, Malhotra A. Association of tirzepatide with changes in OSA-related measures based on baseline characteristics - post hoc analyses of SURMOUNT-OSA. Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine 2026.

Cureus · 2026 · PMID 42388957 · BioNex Evolve (PubMed-indexed)

This review examined tirzepatide, breast cancer risk, and breast imaging using human and preclinical evidence. Human trial data showed no clear evidence of increased breast cancer incidence, while the clinical relevance of reduced tumor progression in preclinical models remains uncertain. Weight loss may change breast appearance and make existing benign lumps easier to feel, without evidence of reduced imaging accuracy.

Citation: Mady R, Tafazal H, Soliman H, Ramadan A, Hajaj M. Clinical Implications of Mounjaro (Tirzepatide) for Breast Cancer Detection and Management: A Narrative Review. Cureus 2026.

Endocrine · 2026 · PMID 42387035 · BioNex Evolve (PubMed-indexed)

This review examined tirzepatide's effects across multiple organs using human clinical trials and preclinical research. Clinical trials showed improved blood sugar control and weight loss compared with existing treatments, alongside improvements in blood fats and liver fat. Potential heart and kidney protection and broader applications require further real-world studies and longer evaluations.

Citation: Khan I, Meenakshi S, Abubakar M, Kumar N, Gaikwad VL, Rai A, Murti K. Tirzepatide as a multi-organ integrator in metabolic diseases: a review of molecular mechanisms and clinical translation. Endocrine 2026.

Frontiers in pharmacology · 2026 · PMID 42683151 · BioNex Evolve (PubMed-indexed)

This review examines tirzepatide in adults with obesity without diabetes, alongside laboratory and translational research on its mechanisms. Human trials showed substantial weight reduction, with reduced appetite and food intake supported as major contributors. Side effects were mainly mild-to-moderate digestive symptoms, while long-term and rare safety outcomes require continued evaluation.

Citation: He WT, Song YD, Wang XY, He SY, Tao X, Yuan SX, Zhou L, Long EW. Tirzepatide for obesity without diabetes: mechanistic insights, clinical evidence, and future directions. Frontiers in pharmacology 2026.

Clinical Medicine Insights. Cardiology · 2026 · PMID 42317617 · BioNex Evolve (PubMed-indexed)

This review examined tirzepatide evidence in people with diabetes, obesity, and related heart or kidney conditions. It reported improved blood sugar, weight, and cardiovascular risk factors, with exploratory evidence of kidney benefits. Major cardiovascular event outcomes were no worse than with dulaglutide, while a trial in obesity-related heart failure found fewer worsening heart failure events and improved health status.

Citation: Parlati AL, Martini L, Nardi E, Carluccio R, Parlati LE, Madaudo C, Perrone Filardi P. Tirzepatide and the Cardiovascular Continuum: Metabolic, Cardiorenal and Heart Failure Evidence. Clinical Medicine Insights. Cardiology 2026.

Expert opinion on drug safety · 2026 · PMID 42201797 · BioNex Evolve (PubMed-indexed)

This review examined human clinical trials and real-world evidence on tirzepatide for type 2 diabetes and obesity. It described blood sugar and weight benefits alongside digestive side effects, a high comparative risk of severe digestive events and treatment discontinuation, and rare gallbladder and thyroid risks. The authors highlighted the need to study long-term physical function and potential muscle loss.

Citation: Janić M, Rabbani SA, El-Tanani M, Rangraze I, Janež A, Maggio V, Rizzo M. Tirzepatide data: safety first is safety always!. Expert opinion on drug safety 2026.

The Journal of clinical endocrinology and metabolism · 2026 · PMID 41866320 · BioNex Evolve (PubMed-indexed)

This retrospective observational study examined tirzepatide use in people with partial lipodystrophy, a condition involving loss or dysfunction of body fat. Tirzepatide use was associated with significant reductions in weight, blood sugar, blood triglycerides, and insulin requirements. The authors called for prospective studies to support these findings.

Citation: Mandour MO, Stears A, Van Der Klaauw A, Flanagan C, Gaff L, Jenkins C, Savage DB. Evaluating the therapeutic impact of tirzepatide in people with partial lipodystrophy. The Journal of clinical endocrinology and metabolism 2026.

Biomedicines · 2026 · PMID 42512116 · BioNex Evolve (PubMed-indexed)

This review examined potential uses of semaglutide and tirzepatide in cancer, mental health and addiction, joint health, skin and appearance, and reproduction. Preclinical research and human observational studies suggested benefits across these areas, but randomized trials were limited. Bone health findings were mixed, and safety concerns around conception remained.

Citation: La Vignera S, Condorelli RA. Unconventional Applications of Semaglutide and Tirzepatide: From Oncology to Human Reproduction. Biomedicines 2026.

Endocrinology, diabetes & metabolism · 2026 · PMID 42673571 · BioNex Evolve (PubMed-indexed)

This analysis combined published human study data to examine weight regain after stopping semaglutide or tirzepatide. Weight regain was rapid and clinically meaningful, with no clear independent difference between the drugs after adjustment. Longer-term predictions relied on an assumed constant rate of regain and should be interpreted cautiously.

Citation: Kow CS, Thiruchelvam K, Ramachandram DS, Zaihan AF. Weight Regain Trajectories After Discontinuation of Semaglutide or Tirzepatide: A Reconstructed Aggregate-Data Bayesian Longitudinal Meta-Analysis. Endocrinology, diabetes & metabolism 2026.

Expert review of clinical pharmacology · 2026 · PMID 42240053 · BioNex Evolve (PubMed-indexed)

This review examined tirzepatide in people with type 1 diabetes, mostly using observational studies involving participants with overweight or obesity. Tirzepatide was associated with improved blood sugar control, weight loss, and reduced insulin requirements, with benefits only partly explained by weight loss. The authors called for randomized trials to confirm these findings.

Citation: Panou T, Gouveri E, Popovic DS, Papanas N. Tirzepatide in type 1 diabetes: beyond mere weight loss. Expert review of clinical pharmacology 2026.

Endocrine · 2026 · PMID 42081121 · BioNex Evolve (PubMed-indexed)

This observational human study tracked the thyroid-related hormone calcitonin during short-term tirzepatide use in adults with obesity and no known thyroid disease. Tirzepatide was associated with a modest but statistically significant increase in calcitonin. Levels remained within the normal range, and no clinically relevant thyroid abnormalities were observed.

Citation: Angelopoulos N, Simeakis G, Androulakis I, Rizoulis A, Boniakos A, Mentzelopoulou P, Korakovouni A, Zianni D, Petkova V, Livadas S, Paparodis R. Short-term effect of tirzepatide on serum calcitonin in adults with obesity. Endocrine 2026.

Diabetes, obesity & metabolism · 2026 · PMID 42410309 · BioNex Evolve (PubMed-indexed)

This review compared cardiovascular outcomes with tirzepatide versus GLP-1 receptor agonists in adults with overweight or obesity. Tirzepatide was not associated with a statistically significant reduction in major cardiovascular events. Substantial differences between studies and the predominance of observational evidence limit conclusions about cause and effect.

Citation: Silva JPMRJ, Nogueira BV, Sartori DL, da Silva JRC, Sciota LBA, de Mendonça Bisneto OI, Gomes WF. Cardiovascular Outcomes With Tirzepatide Versus GLP-1 Receptor Agonists in Overweight or Obesity: A Systematic Review and Meta-Analysis. Diabetes, obesity & metabolism 2026.

Diabetes, obesity & metabolism · 2026 · PMID 42050884 · BioNex Evolve (PubMed-indexed)

This analysis indirectly compared separate trials of injectable tirzepatide and oral semaglutide in adults with overweight or obesity without type 2 diabetes. Some tirzepatide regimens were associated with significantly greater weight and waist reductions, while cardiovascular and metabolic benefits and safety were improved or generally comparable. This was not a direct head-to-head trial.

Citation: Ciudin A, Johansson E, Zimner-Rapuch S, Dimitriadis GK, Hempfling M, Clark LJ, Fan L, Sapin H. Indirect Comparative Efficacy and Safety of Tirzepatide Versus Oral Semaglutide for the Treatment of Overweight and Obesity. Diabetes, obesity & metabolism 2026.

Journal of the American College of Cardiology · 2026 · PMID 42233927 · BioNex Evolve (PubMed-indexed)

This follow-up analysis of a human trial compared cardiovascular risk markers in blood samples from adults with overweight or obesity receiving tirzepatide or placebo. Tirzepatide was associated with improvements in markers of metabolism, body fat, liver stress, and blood vessel function, plus selected inflammation and clotting markers. The analysis examined biomarkers rather than cardiovascular events.

Citation: Sattar N, Linetzky B, Ruotolo G, Verma S, Sourij H, Wang H, Vanderman K, Wilson JM, Griffin RM, Stefanski A, Ridker PM. Comprehensive Long-Term Changes in Cardiovascular Risk Biomarkers With Tirzepatide: A SURMOUNT-1 Post Hoc Analysis. Journal of the American College of Cardiology 2026.

ClinicalTrials.gov · 2026 · NCT07589322 · ClinicalTrials.gov

This recruiting randomized human trial directly compares tirzepatide and semaglutide in adults with obesity and metabolic syndrome. Researchers are measuring body composition, liver fat, strength, heart-related measures, and biological markers; no results are reported.

Population / model

Obesity and Metabolic Syndrome

Citation: Tri-Service General Hospital (TSGH). Comparative Adipose Tissue and Cardiometabolic System Remodeling by Tirzepatide and Semaglutide: an AI-integrated Multimodal Metabolomics and Translational Mechanistic Study. ClinicalTrials.gov 2026.

ClinicalTrials.gov · 2026 · NCT07702461 · ClinicalTrials.gov

This recruiting human observational study uses an anonymous survey to examine adults’ strength-training habits before and after starting GLP-1 medications. It also explores links with self-reported strength and daily function, along with barriers to training; no results are reported.

Population / model

Obesity & Overweight; Diabetes (DM)

Citation: Ohio State University. Determination of Resistance Training Status for Patients on Glucagon-Like Peptide-1 Receptor Agonists. ClinicalTrials.gov 2026.

ClinicalTrials.gov · 2026 · NCT07653412 · ClinicalTrials.gov

This recruiting human observational study will follow adults with obesity starting semaglutide or tirzepatide to investigate whether genetic risk scores and selected genetic variants can predict weight-loss response. Researchers plan to combine genetic and clinical information in prediction models; no results are reported.

Population / model

Obesity (Disorder); Anti-obesity Agents; Precision Medicine

Citation: National and Kapodistrian University of Athens. Prediction of Response to GLP-1/GIP Receptor Agonists in Obesity Using Genetic Risk Score and SNP Profiling: A Prospective Cohort Study.. ClinicalTrials.gov 2026.

ClinicalTrials.gov · 2026 · NCT07640139 · ClinicalTrials.gov

This human observational study uses existing insurance records to compare adults with employer-provided insurance who have obesity-medication prescriptions with those who do not. It is enrolling by invitation and will examine associations with weight, health, healthcare use, and economic outcomes; no results are reported.

Population / model

Obesity

Citation: Indiana University. Estimating the Impact of Obesity Medications on Clinical and Economic Outcomes. ClinicalTrials.gov 2026.

Lancet (London, England) · 2026 · PMID 42119587 · PubMed

This completed randomized human trial studied weight-loss maintenance after initial tirzepatide treatment in adults with obesity or overweight and a weight-related condition. Both continued tirzepatide regimens maintained greater weight reduction from the original baseline than switching to placebo. The supplied abstract is truncated and does not include safety results.

Citation: Horn DB, Aronne LJ, Wharton S, Bays HE, le Roux CW, Srinath R, Gomez-Valderas E, Arad AD, Das S, Dunn JP, Ribeiro A, Glass LC et al.. Tirzepatide for maintenance of bodyweight reduction in people with obesity in the USA (SURMOUNT-MAINTAIN): a multicentre, double-blind, randomised, placebo-controlled trial.. Lancet (London, England) 2026.

JAMA internal medicine · 2026 · PMID 41284285 · PubMed

This follow-up analysis examined adults with obesity who lost weight on tirzepatide and then switched to placebo in a randomized trial. Greater weight regain after withdrawal was associated with larger increases in waist size, blood pressure, certain cholesterol measures, and average blood sugar.

Citation: Horn DB, Linetzky B, Davies MJ, Laffin LJ, Wang H, Murphy MA, Zimner-Rapuch S, Lau E, Arad AD, Lee CJ. Cardiometabolic Parameter Change by Weight Regain on Tirzepatide Withdrawal in Adults With Obesity: A Post Hoc Analysis of the SURMOUNT-4 Trial.. JAMA internal medicine 2026.

The lancet. Diabetes & endocrinology · 2026 · PMID 42114520 · PubMed

This exploratory analysis of a randomized trial compared kidney outcomes with tirzepatide and dulaglutide in people with type 2 diabetes and cardiovascular disease. Tirzepatide reduced the risk of a combined outcome of persistent high urine protein, major kidney function decline, kidney failure, or kidney-related death. Reductions were seen in both lower-risk and high-risk kidney disease groups.

Citation: Zoungas S, D'Alessio D, Pavo I, Bhatt DL, Buse JB, Prato SD, Kahn SE, Lincoff AM, McGuire DK, Nauck MA, Nissen SE, Sattar N et al.. A comparison of the effects of tirzepatide and dulaglutide on major kidney events in people with type 2 diabetes: pre-specified exploratory analyses of the SURPASS-CVOT trial.. The lancet. Diabetes & endocrinology 2026.

Advances in therapy · 2026 · PMID 41820778 · PubMed

This systematic review and indirect comparison of randomized human trials assessed tirzepatide, liraglutide, and semaglutide in adults with overweight or obesity without type 2 diabetes. Tirzepatide was associated with greater weight reduction than liraglutide; comparisons with semaglutide varied by regimen, with some favoring tirzepatide. The treatments had generally comparable safety profiles.

Citation: Ciudin A, Sapin H, Fan L, Dimitriadis GK, Zimner-Rapuch S, Curteis T, Clark LJ, Rubinstein M, Johansson E. Comparison of Clinical Efficacy and Safety of Tirzepatide, Liraglutide and Semaglutide in Patients with Obesity and Without T2D: A Bayesian Network Meta-Analysis of Randomised Controlled Trials.. Advances in therapy 2026.

ClinicalTrials.gov · 2026 · NCT07382024 · ClinicalTrials.gov

This registered randomized human trial will test whether tirzepatide reduces persistent atrial fibrillation, an irregular heart rhythm, after catheter ablation in adults with overweight or obesity. It will also assess weight, metabolic health, and safety compared with standard care alone. The trial is not yet recruiting, and no results are available.

Population / model

Atrial Fibrillation Ablation; Persistent Atrial Fibrillation; Obesity & Overweight

Citation: National Taiwan University Hospital. Tirzepatide to Reduce Recurrence and Burden After Catheter Ablation of Atrial Fibrillation: A Prospective Randomized Trial. ClinicalTrials.gov 2026.

ClinicalTrials.gov · 2026 · NCT07734870 · ClinicalTrials.gov

This recruiting pilot human trial is studying tirzepatide in adults with active central centrifugal cicatricial alopecia, a form of permanent scarring hair loss. Researchers will assess scalp symptoms, scarring-related gene activity, and hair regrowth, comparing participants with their own starting measurements rather than a separate control group. No results are available.

Population / model

Central Centrifugal Cicatricial Alopecia (CCCA)

Citation: Johns Hopkins University. Tirzepatide for Treatment of CCCA. ClinicalTrials.gov 2026.

ClinicalTrials.gov · 2026 · NCT07650149 · ClinicalTrials.gov

This registered observational study is examining how genetic markers, gut microbes, and behavioral factors relate to tirzepatide tolerability, continued use, and effectiveness in people with obesity. The study is recruiting, and no results are reported.

Population / model

Obesity & Overweight; Obesity; Genetics

Citation: Jan Kochanowski University. OPTIMIZE GEN - Outcomes of Persistence and Treatment With tIrzepatide deterMined by Genetic, mIcrobiological & bEhavioral Factors in obEsity. ClinicalTrials.gov 2026.

ClinicalTrials.gov · 2026 · NCT07817875 · ClinicalTrials.gov

This registered randomized trial will compare tirzepatide with placebo alongside a healthy lifestyle program in children with obesity. It will assess effectiveness, safety, and how the body processes tirzepatide. The trial has not yet started recruiting, and no results are reported.

Population / model

Obesity

Citation: Eli Lilly and Company. Efficacy, Safety, and Pharmacokinetics of Tirzepatide Once Weekly Versus Placebo in Pediatric Participants 6 to Less Than 12 Years of Age Who Have Obesity: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Trial. ClinicalTrials.gov 2026.

ClinicalTrials.gov · 2026 · NCT07065552 · ClinicalTrials.gov

This registered human trial is examining whether tirzepatide affects cancer cell growth before surgery in patients with obesity-driven endometrial cancer. Researchers will compare tumor tissue collected before and after treatment. The trial is recruiting, and no results are reported; potential effects on tumor growth remain a hypothesis.

Population / model

Endometrial Cancer; Obesity

Citation: UNC Lineberger Comprehensive Cancer Center. A Pre-Operative Window Study of Tirzepatide in Obesity-Driven Endometrial Cancer. ClinicalTrials.gov 2026.

ClinicalTrials.gov · 2026 · NCT07559500 · ClinicalTrials.gov

This ongoing human trial is studying how tirzepatide affects brain responses in people with alcohol use disorder and healthy volunteers, using brain scans and a placebo comparison. Researchers want to understand whether it may lessen the urge to drink. The trial is recruiting, and no results are reported.

Population / model

Alcohol Use Disorder (AUD)

Citation: National Institute on Alcohol Abuse and Alcoholism (NIAAA). Tirzepatide s Dopaminergic Effects in Alcohol Use Disorders (AUD), a Phase 1b Study. ClinicalTrials.gov 2026.

The New England journal of medicine · 2025 · PMID 40353578 · BioNex Evolve (PubMed-indexed)

This randomized, open-label trial compared tirzepatide with semaglutide in adults with obesity but without type 2 diabetes. Tirzepatide produced greater reductions in body weight and waist circumference. Digestive side effects were the most common in both groups and were generally mild to moderate.

Citation: Aronne LJ, Horn DB, le Roux CW, Ho W, Falcon BL, Gomez Valderas E, Das S, Lee CJ, Glass LC, Senyucel C, Dunn JP. Tirzepatide as Compared with Semaglutide for the Treatment of Obesity.. The New England journal of medicine 2025.

ClinicalTrials.gov · 2025 · NCT06847399 · ClinicalTrials.gov

This recruiting human trial is comparing tirzepatide with placebo or lisdexamfetamine in adults with obesity and binge-eating disorder. All participants will also receive guided self-help cognitive behavioral therapy. The trial is ongoing, and no results are reported.

Population / model

Obesity and Overweight; Binge Eating Disorder

Citation: Johns Hopkins University. Efficacy and Safety of Tirzepatide Versus Placebo or Lisdexamfetamine Dimesylate for Binge-Eating Disorder: A Randomized Clinical Trial. ClinicalTrials.gov 2025.

ClinicalTrials.gov · 2025 · NCT06856928 · ClinicalTrials.gov

This planned human observational study will examine appetite and food intake in people starting obesity medications such as semaglutide or tirzepatide and people who have maintained substantial weight loss. It will test study methods and gather preliminary data for future research; recruitment has not started and no results are reported.

Population / model

Obesity; Drug

Citation: University of Colorado, Denver. Impact of Antiobesity Medications on Appetite and Appetite-related Hormones and Metabolites.. ClinicalTrials.gov 2025.

The New England journal of medicine · 2025 · PMID 39555826 · PubMed

This randomized human trial compared tirzepatide with placebo in patients with obesity and heart failure with preserved ejection fraction. Tirzepatide lowered the combined risk of cardiovascular death or worsening heart failure and improved health status. Side effects leading to treatment discontinuation, mainly digestive problems, were more common with tirzepatide.

Citation: Packer M, Zile MR, Kramer CM, Baum SJ, Litwin SE, Menon V, Ge J, Weerakkody GJ, Ou Y, Bunck MC, Hurt KC, Murakami M et al.. Tirzepatide for Heart Failure with Preserved Ejection Fraction and Obesity.. The New England journal of medicine 2025.

The New England journal of medicine · 2025 · PMID 41406444 · PubMed

This randomized human trial compared tirzepatide with dulaglutide in patients with type 2 diabetes and cardiovascular disease caused by narrowed arteries. Tirzepatide met the study's criterion for being no worse than dulaglutide for the combined outcome of cardiovascular death, heart attack, or stroke, but superiority was not established. Digestive side effects were more common with tirzepatide.

Citation: Nicholls SJ, Pavo I, Bhatt DL, Buse JB, Del Prato S, Kahn SE, Lincoff AM, McGuire DK, Miller D, Nauck MA, Nishiyama H, Nissen SE et al.. Cardiovascular Outcomes with Tirzepatide versus Dulaglutide in Type 2 Diabetes.. The New England journal of medicine 2025.

The New England journal of medicine · 2025 · PMID 39536238 · PubMed

This randomized human trial analysis compared tirzepatide with placebo in participants with obesity and prediabetes. Tirzepatide produced substantial, sustained weight reduction and a markedly lower risk of progression to type 2 diabetes. Digestive side effects were common and mostly mild to moderate, and no new safety signals were identified.

Citation: Jastreboff AM, le Roux CW, Stefanski A, Aronne LJ, Halpern B, Wharton S, Wilding JPH, Perreault L, Zhang S, Battula R, Bunck MC, Ahmad NN et al.. Tirzepatide for Obesity Treatment and Diabetes Prevention.. The New England journal of medicine 2025.

Diabetes, obesity & metabolism · 2025 · PMID 39996356 · PubMed

This substudy of a randomized human trial examined body composition in adults with obesity or overweight. Tirzepatide significantly reduced body weight, fat mass, and lean mass compared with placebo. The proportions of weight lost as fat and lean tissue were similar between groups and relatively consistent across most participant subgroups.

Citation: Look M, Dunn JP, Kushner RF, Cao D, Harris C, Gibble TH, Stefanski A, Griffin R. Body composition changes during weight reduction with tirzepatide in the SURMOUNT-1 study of adults with obesity or overweight.. Diabetes, obesity & metabolism 2025.

Sleep medicine · 2025 · PMID 40774158 · PubMed

This analysis of randomized human trials examined self-reported outcomes in people with moderate-to-severe obstructive sleep apnea and obesity. Compared with placebo, tirzepatide significantly improved reported sleep disturbance, sleep-related difficulties, activity levels, and several quality-of-life measures. It was also associated with greater improvements in self-rated sleep apnea symptoms.

Citation: Kanu C, Shinde S, Chakladar S, Dennehy EB, Weaver TE, Poon JL, Malhotra A. Effect of tirzepatide treatment on patient-reported outcomes among SURMOUNT-OSA participants with obstructive sleep apnea and obesity.. Sleep medicine 2025.

Diabetes, obesity & metabolism · 2025 · PMID 40365662 · PubMed

This analysis of a randomized human trial assessed quality of life in adults with obesity or overweight who had already lost weight through an intensive lifestyle program. Tirzepatide was associated with significantly greater improvements than placebo on most quality-of-life measures. Improvements were generally larger among those losing more weight and those with physical limitations at the start.

Citation: Gibble TH, Cao D, Forrester T, Fraseur Brumm J, Chao AM. Tirzepatide and health-related quality of life in adults with obesity or overweight: Results from the SURMOUNT-3 phase 3 randomized trial.. Diabetes, obesity & metabolism 2025.

Obesity reviews : an official journal of the International Association for the Study of Obesity · 2025 · PMID 40186344 · PubMed

This systematic review and meta-analysis combined randomized human trials examining weight changes after stopping GLP-1-based medicines, including tirzepatide, in people with overweight or obesity. Significant weight regain occurred after stopping treatment. Weight regain was proportional to the weight originally lost.

Citation: Berg S, Stickle H, Rose SJ, Nemec EC. Discontinuing glucagon-like peptide-1 receptor agonists and body habitus: A systematic review and meta-analysis.. Obesity reviews : an official journal of the International Association for the Study of Obesity 2025.

Metabolism: clinical and experimental · 2025 · PMID 39719170 · PubMed

This systematic review and meta-analysis examined body composition in randomized trials of GLP-1-based medicines in adults with diabetes, overweight, or obesity. Overall, these medicines significantly reduced body weight, fat mass, and lean tissue mass. Tirzepatide and semaglutide were most effective for weight and fat reduction but were among the least effective at preserving lean tissue.

Citation: Karakasis P, Patoulias D, Fragakis N, Mantzoros CS. Effect of glucagon-like peptide-1 receptor agonists and co-agonists on body composition: Systematic review and network meta-analysis.. Metabolism: clinical and experimental 2025.

Journal of the American College of Cardiology · 2025 · PMID 40162940 · PubMed

This randomized trial analysis studied tirzepatide in people with obesity and heart failure with preserved pumping function, with or without chronic kidney disease. Kidney disease did not alter tirzepatide’s relative benefits for heart failure events, quality of life, or physical function. Estimated kidney function improved over longer follow-up, although results differed between measurement methods and may be affected by changes in body composition.

Citation: Packer M, Zile MR, Kramer CM, Murakami M, Ou Y, Borlaug BA. Interplay of Chronic Kidney Disease and the Effects of Tirzepatide in Patients With Heart Failure, Preserved Ejection Fraction, and Obesity: The SUMMIT Trial.. Journal of the American College of Cardiology 2025.

Diabetes, obesity & metabolism · 2025 · PMID 39497468 · PubMed

This analysis of a randomized trial examined weight loss and self-reported quality of life in adults with overweight or obesity. Tirzepatide was associated with improved health-related quality of life compared with placebo, and greater weight loss was associated with greater improvements. Participants with physical or psychosocial limitations at the start experienced larger improvements.

Citation: Gudzune KA, Stefanski A, Cao D, Mojdami D, Wang F, Ahmad N, Ling Poon J. Association between weight reduction achieved with tirzepatide and quality of life in adults with obesity: Results from the SURMOUNT-1 study.. Diabetes, obesity & metabolism 2025.

International journal of obesity (2005) · 2025 · PMID 40804463 · PubMed

This systematic review compared digestive side effects of weight-management medicines in people with overweight or obesity without diabetes. Nausea, vomiting, diarrhea, and constipation were the most common digestive side effects, with risks differing between medicines. Tirzepatide was associated with increased risks of nausea and vomiting.

Citation: Ismaiel A, Scarlata GGM, Boitos I, Leucuta DC, Popa SL, Al Srouji N, Abenavoli L, Dumitrascu DL. Gastrointestinal adverse events associated with GLP-1 RA in non-diabetic patients with overweight or obesity: a systematic review and network meta-analysis.. International journal of obesity (2005) 2025.

ClinicalTrials.gov · 2025 · NCT06965413 · ClinicalTrials.gov

This registered randomized trial compares RO7204239 plus tirzepatide with placebo plus tirzepatide for weight loss in adults without diabetes who have obesity or overweight with a weight-related condition. The trial is ongoing but no longer recruiting. No results are reported.

Population / model

Obesity; Overweight; Overweight With One Weight Related Comorbidity

Citation: Hoffmann-La Roche. A Randomized, Double-blind, Placebo-controlled Phase 2 Trial to Assess Efficacy, Safety, and Tolerability of RO7204239 in Combination With Tirzepatide in Participants With Obesity or Overweight With At Least One Weight-related Comorbidity. ClinicalTrials.gov 2025.

ClinicalTrials.gov · 2025 · NCT06801015 · ClinicalTrials.gov

This registered randomized human trial compares semaglutide, tirzepatide, and placebo for their effects on stomach emptying, the stomach’s ability to expand, and feelings of fullness. The trial is ongoing but no longer recruiting. No results are reported.

Population / model

Obesity

Citation: Mayo Clinic. A Randomized, Placebo-Controlled Trial of the Effects of Long-Acting GLP-1 or Dual Incretin (GLP-1 and GIP) Modulation on Gastric Motor Functions. ClinicalTrials.gov 2025.

ClinicalTrials.gov · 2025 · NCT06893211 · ClinicalTrials.gov

This completed human trial compared tirzepatide with placebo in women with obesity to test whether it increases the activity of energy-burning brown and beige fat. Researchers also planned to assess weight and metabolic changes. The abstract describes the study goals and methods but reports no results.

Population / model

Obesity

Citation: University Medical Centre Ljubljana. Effect of Tirzepatide-Induced Weight Loss on Adipose Tissue in Obesity. ClinicalTrials.gov 2025.

JAMA internal medicine · 2024 · PMID 38976257 · BioNex Evolve (PubMed-indexed)

This observational study compared tirzepatide and semaglutide using health records of adults with overweight or obesity. Tirzepatide use was associated with significantly greater weight loss while patients remained on treatment. Rates of gastrointestinal side effects were similar between groups.

Citation: Rodriguez PJ, Goodwin Cartwright BM, Gratzl S, Brar R, Baker C, Gluckman TJ, Stucky NL. Semaglutide vs Tirzepatide for Weight Loss in Adults With Overweight or Obesity.. JAMA internal medicine 2024.

Drugs · 2024 · PMID 38388874 · BioNex Evolve (PubMed-indexed)

This review examined tirzepatide trials in adults with inadequately controlled type 2 diabetes. In the comparisons studied, tirzepatide improved blood sugar control and weight loss more than dulaglutide, semaglutide, or insulin. It was generally well tolerated; the most common side effects were digestive problems, usually mild to moderate.

Citation: France NL, Syed YY. Tirzepatide: A Review in Type 2 Diabetes.. Drugs 2024.

JAMA · 2024 · PMID 38078870 · PubMed

This randomized human trial studied weight-loss maintenance in adults with obesity or overweight and a weight-related complication, without diabetes, after initial tirzepatide treatment. Switching to placebo led to substantial weight regain, while continuing tirzepatide maintained and increased the initial weight loss. Digestive side effects were more common with tirzepatide and were mostly mild to moderate.

Citation: Aronne LJ, Sattar N, Horn DB, Bays HE, Wharton S, Lin WY, Ahmad NN, Zhang S, Liao R, Bunck MC, Jouravskaya I, Murphy MA. Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4 Randomized Clinical Trial.. JAMA 2024.

The New England journal of medicine · 2024 · PMID 38912654 · PubMed

Randomized human trials compared tirzepatide with placebo in adults with obesity and moderate-to-severe obstructive sleep apnea, with or without positive airway pressure therapy. Tirzepatide reduced breathing interruptions, body weight, low-oxygen burden, an inflammation marker, and systolic blood pressure, and improved patient-reported sleep outcomes. The most common side effects were digestive and mostly mild to moderate.

Citation: Malhotra A, Grunstein RR, Fietze I, Weaver TE, Redline S, Azarbarzin A, Sands SA, Schwab RJ, Dunn JP, Chakladar S, Bunck MC, Bednarik J. Tirzepatide for the Treatment of Obstructive Sleep Apnea and Obesity.. The New England journal of medicine 2024.

The New England journal of medicine · 2024 · PMID 38856224 · PubMed

This randomized human trial studied tirzepatide in people with metabolic dysfunction-associated steatohepatitis (MASH), a liver disease, and moderate or severe liver scarring. Tirzepatide was more effective than placebo at resolving MASH without worsening scarring. Digestive side effects were mostly mild or moderate, and larger, longer trials are needed to assess effectiveness and safety further.

Citation: Loomba R, Hartman ML, Lawitz EJ, Vuppalanchi R, Boursier J, Bugianesi E, Yoneda M, Behling C, Cummings OW, Tang Y, Brouwers B, Robins DA et al.. Tirzepatide for Metabolic Dysfunction-Associated Steatohepatitis with Liver Fibrosis.. The New England journal of medicine 2024.

JAMA · 2024 · PMID 38819983 · PubMed

This randomized trial compared tirzepatide with placebo, both alongside a lifestyle program, in Chinese adults with obesity or overweight and weight-related conditions, excluding diabetes. Tirzepatide produced statistically significant and clinically meaningful weight loss. The most frequent side effects affected the digestive system and were mostly mild to moderate.

Citation: Zhao L, Cheng Z, Lu Y, Liu M, Chen H, Zhang M, Wang R, Yuan Y, Li X. Tirzepatide for Weight Reduction in Chinese Adults With Obesity: The SURMOUNT-CN Randomized Clinical Trial.. JAMA 2024.

Diabetes, obesity & metabolism · 2024 · PMID 37932236 · PubMed

This post hoc analysis of a randomized trial assessed predicted cardiovascular risk in adults with overweight or obesity without diabetes. Tirzepatide improved cardiovascular and metabolic risk factors and reduced predicted risk of artery-related cardiovascular disease compared with placebo. These findings concern calculated risk scores, not demonstrated reductions in actual cardiovascular events.

Citation: Hankosky ER, Wang H, Neff LM, Kan H, Wang F, Ahmad NN, Griffin R, Stefanski A, Garvey WT. Tirzepatide reduces the predicted risk of atherosclerotic cardiovascular disease and improves cardiometabolic risk factors in adults with obesity or overweight: SURMOUNT-1 post hoc analysis.. Diabetes, obesity & metabolism 2024.

ClinicalTrials.gov · 2024 · NCT06162715 · ClinicalTrials.gov

This registered pilot trial compares tirzepatide with standard care in people who still have obesity after gastric bypass surgery. It is assessing effectiveness and the frequency of side effects. The trial is ongoing but no longer recruiting, and no results are reported.

Population / model

Severe Obesity; Obesity; BMI Greater Than 30

Citation: Vanderbilt University Medical Center. GLP-1 Receptor Agonists Post-Bariatric Surgery (GRABS) Pilot Trial. ClinicalTrials.gov 2024.

ClinicalTrials.gov · 2024 · NCT06648031 · ClinicalTrials.gov

This registered randomized human trial compared DehydraTECH cannabidiol and GLP-1 medicines, alone and together, in people with overweight or obesity and prediabetes or type 2 diabetes. It assessed safety, how the body processes these substances, and effectiveness. The study is completed, but no results are provided in this record.

Population / model

Type2diabetes

Citation: Lexaria Bioscience Corp.. A Phase 1B, Randomized, Open-label, Active-controlled, Parallel, Multiple-dose Study Comparing the Safety, Pharmacokinetics and Efficacy of Dehydratech Cannabidiol and Glucagon-like Peptide 1 Agonists Alone and in Combination, in Overweight or Obese, pre-and Type 2 Diabetic Participants.. ClinicalTrials.gov 2024.

ClinicalTrials.gov · 2024 · NCT06588283 · ClinicalTrials.gov

This completed randomized human trial compared ixekizumab plus tirzepatide with ixekizumab alone in adults with moderate-to-severe plaque psoriasis and obesity or overweight with a weight-related condition. It aimed to assess improvements in psoriasis and weight reduction, but the abstract reports no results.

Population / model

Psoriasis; Obesity

Citation: Eli Lilly and Company. Efficacy and Safety of Ixekizumab or Ixekizumab Concomitantly Administered With Tirzepatide in Adult Participants With Moderate-to-Severe Plaque Psoriasis and Obesity or Overweight: A Phase 3b, Randomized, Multicenter, Open-Label Study (TOGETHER-PsO). ClinicalTrials.gov 2024.

ClinicalTrials.gov · 2024 · NCT07701005 · ClinicalTrials.gov

This completed observational study reviewed records of adults with overweight or obesity who received semaglutide or tirzepatide at a Turkish medical center. Researchers assessed changes in indirect measures of liver scarring, liver fat, and insulin resistance. The abstract describes the analysis but reports no findings.

Population / model

Steatosis of Liver; Metabolic Liver Injury; Obesity; Overweight; Insulin Resistance

Citation: Goztepe Prof Dr Suleyman Yalcın City Hospital. Early Changes in Non-Invasive Hepatic and Metabolic Indices After Incretin-Based Therapy in Patients With Overweight or Obesity: Real-World Evidence From a Turkish Cohort. ClinicalTrials.gov 2024.

The Senior care pharmacist · 2023 · PMID 36751934 · BioNex Evolve (PubMed-indexed)

This overview discusses tirzepatide and the SURPASS clinical trials in people with type 2 diabetes. The trials demonstrated strong blood sugar lowering and weight loss, with adverse effects comparable to those of GLP-1 receptor agonists.

Citation: Gettman L. New Drug: Tirzepatide (Mounjaro™).. The Senior care pharmacist 2023.

Frontiers in endocrinology · 2023 · PMID 37908750 · BioNex Evolve (PubMed-indexed)

This systematic review combined randomized human trials examining tirzepatide safety in type 2 diabetes and obesity. Tirzepatide was not significantly associated with increased pancreatitis risk. However, a combined measure of gallbladder or bile duct diseases showed increased risk compared with placebo or basal insulin.

Citation: Zeng Q, Xu J, Mu X, Shi Y, Fan H, Li S. Safety issues of tirzepatide (pancreatitis and gallbladder or biliary disease) in type 2 diabetes and obesity: a systematic review and meta-analysis.. Frontiers in endocrinology 2023.

International journal of obesity (2005) · 2023 · PMID 37253796 · BioNex Evolve (PubMed-indexed)

This systematic review and meta-analysis combined randomized trials of tirzepatide in people with overweight or obesity. Tirzepatide produced greater weight loss than placebo and semaglutide in the included comparisons. Gastrointestinal adverse events were more likely than with placebo, but did not differ significantly from semaglutide.

Citation: Tan B, Pan XH, Chew HSJ, Goh RSJ, Lin C, Anand VV, Lee ECZ, Chan KE, Kong G, Ong CEY, Chung HC, Young DY. Efficacy and safety of tirzepatide for treatment of overweight or obesity. A systematic review and meta-analysis.. International journal of obesity (2005) 2023.

Lancet (London, England) · 2023 · PMID 37385275 · PubMed

This randomized human trial compared tirzepatide with placebo for weight management in adults with overweight or obesity and type 2 diabetes. Tirzepatide produced substantially greater weight reduction than placebo. The most common side effects included nausea, diarrhea, and vomiting, and were mostly mild to moderate.

Citation: Garvey WT, Frias JP, Jastreboff AM, le Roux CW, Sattar N, Aizenberg D, Mao H, Zhang S, Ahmad NN, Bunck MC, Benabbad I, Zhang XM. Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial.. Lancet (London, England) 2023.

ClinicalTrials.gov · 2023 · NCT06009653 · ClinicalTrials.gov

This registered trial planned to study tirzepatide combined with a culturally tailored lifestyle program in Latino adults with obesity. It aimed to assess weight loss, metabolic health, and participation in the program. The trial was withdrawn, and no results are reported.

Population / model

Obesity; Metabolic Disease

Citation: Washington University School of Medicine. Effect of Tirzepatide Plus Intensive Lifestyle Therapy on Body Weight and Metabolic Health in Latinos With Obesity. ClinicalTrials.gov 2023.

International journal of molecular sciences · 2022 · PMID 36498958 · BioNex Evolve (PubMed-indexed)

This systematic review summarized human clinical trials and meta-analyses of tirzepatide, primarily for diabetes. It reported improved blood sugar control and blood pressure, along with reductions in LDL cholesterol and triglycerides. Potential cardiovascular applications were discussed, while trials in other diseases were ongoing.

Citation: Forzano I, Varzideh F, Avvisato R, Jankauskas SS, Mone P, Santulli G. Tirzepatide: A Systematic Update.. International journal of molecular sciences 2022.

JAMA · 2022 · PMID 35133415 · BioNex Evolve (PubMed-indexed)

This randomized trial compared tirzepatide with placebo added to insulin glargine in adults whose type 2 diabetes was inadequately controlled. Tirzepatide significantly improved blood sugar control and reduced body weight compared with placebo. Diarrhea and nausea were the most common adverse events reported with tirzepatide.

Citation: Dahl D, Onishi Y, Norwood P, Huh R, Bray R, Patel H, Rodríguez Á. Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes: The SURPASS-5 Randomized Clinical Trial.. JAMA 2022.

Journal of cardiovascular pharmacology · 2022 · PMID 35767712 · BioNex Evolve (PubMed-indexed)

This review examines tirzepatide’s effects on blood sugar, weight, and heart and metabolic health, drawing on human trials in type 2 diabetes. Preliminary data suggest that tirzepatide is effective and safe for treating type 2 diabetes. The most common side effects were gastrointestinal symptoms, which generally carried a low risk of stopping treatment.

Citation: Bucheit J, Ayers J, Pamulapati L, Browning A, Sisson E. A Novel Dual Incretin Agent, Tirzepatide (LY3298176), for the Treatment of Type 2 Diabetes Mellitus and Cardiometabolic Health. Journal of cardiovascular pharmacology 2022.

ClinicalTrials.gov · 2022 · NCT05766358 · ClinicalTrials.gov

This completed observational follow-up study examined whether changes in energy use during weight loss were associated with later weight regain and body composition in people with obesity. Participants had previously received tirzepatide or placebo during a lifestyle intervention; the abstract describes planned comparisons but reports no results.

Population / model

Weight Loss; Weight Gain; Obesity

Citation: Pennington Biomedical Research Center. Role Of Metabolic Adaptation In Weight Regain: Expend Follow-Up. ClinicalTrials.gov 2022.

ClinicalTrials.gov · 2022 · NCT05564039 · ClinicalTrials.gov

This completed randomized trial in adults with type 2 diabetes investigated the effectiveness and safety of switching from dulaglutide to tirzepatide compared with adjusting dulaglutide treatment. The supplied abstract describes the study purpose but reports no results.

Population / model

Type 2 Diabetes

Citation: Eli Lilly and Company. A Phase 4, Randomized, Open-Label, Active-Controlled Study to Investigate the Efficacy and Safety of Switching From Weekly Dulaglutide to Weekly Tirzepatide in Adults With Type 2 Diabetes. ClinicalTrials.gov 2022.

The New England journal of medicine · 2022 · PMID 35658024 · PubMed

This randomized trial compared tirzepatide with placebo in adults with obesity or overweight and weight-related complications, excluding diabetes. Tirzepatide produced substantial, sustained weight loss and improvements in measures of heart and metabolic health. The most common side effects affected the digestive system and were mostly mild to moderate.

Citation: Jastreboff AM, Aronne LJ, Ahmad NN, Wharton S, Connery L, Alves B, Kiyosue A, Zhang S, Liu B, Bunck MC, Stefanski A. Tirzepatide Once Weekly for the Treatment of Obesity.. The New England journal of medicine 2022.

The lancet. Diabetes & endocrinology · 2022 · PMID 36152639 · PubMed

This follow-up analysis of a randomized human trial compared kidney outcomes with tirzepatide and insulin glargine in adults with type 2 diabetes and high cardiovascular risk. Kidney filtration declined more slowly with tirzepatide. A urine marker of protein leakage increased with insulin glargine but not with tirzepatide.

Citation: Heerspink HJL, Sattar N, Pavo I, Haupt A, Duffin KL, Yang Z, Wiese RJ, Tuttle KR, Cherney DZI. Effects of tirzepatide versus insulin glargine on kidney outcomes in type 2 diabetes in the SURPASS-4 trial: post-hoc analysis of an open-label, randomised, phase 3 trial.. The lancet. Diabetes & endocrinology 2022.

The lancet. Diabetes & endocrinology · 2022 · PMID 35914543 · PubMed

This randomized trial compared tirzepatide with dulaglutide in Japanese adults with type 2 diabetes. Tirzepatide produced greater reductions in average blood sugar and body weight. Commonly reported side effects included nausea, constipation, and nose and throat inflammation.

Citation: Inagaki N, Takeuchi M, Oura T, Imaoka T, Seino Y. Efficacy and safety of tirzepatide monotherapy compared with dulaglutide in Japanese patients with type 2 diabetes (SURPASS J-mono): a double-blind, multicentre, randomised, phase 3 trial.. The lancet. Diabetes & endocrinology 2022.

Lancet (London, England) · 2021 · PMID 34186022 · BioNex Evolve (PubMed-indexed)

This randomized trial compared tirzepatide with placebo in adults whose type 2 diabetes was inadequately controlled by diet and exercise alone. Tirzepatide improved blood sugar measures and reduced body weight more than placebo. The most frequent side effects were temporary, mild-to-moderate digestive symptoms; no clinically significant or severe low blood sugar was reported with tirzepatide.

Citation: Rosenstock J, Wysham C, Frías JP, Kaneko S, Lee CJ, Fernández Landó L, Mao H, Cui X, Karanikas CA, Thieu VT. Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1): a double-blind, randomised, phase 3 trial.. Lancet (London, England) 2021.

The Journal of clinical endocrinology and metabolism · 2021 · PMID 33236115 · PubMed

This follow-up analysis of a human trial examined blood markers of insulin sensitivity and insulin-producing cell function in people with type 2 diabetes. Tirzepatide improved these markers more than dulaglutide. Improvements in insulin sensitivity were only partly attributable to weight loss, suggesting additional mechanisms of blood sugar control.

Citation: Thomas MK, Nikooienejad A, Bray R, Cui X, Wilson J, Duffin K, Milicevic Z, Haupt A, Robins DA. Dual GIP and GLP-1 Receptor Agonist Tirzepatide Improves Beta-cell Function and Insulin Sensitivity in Type 2 Diabetes.. The Journal of clinical endocrinology and metabolism 2021.

JCI insight · 2020 · PMID 32730231 · BioNex Evolve (PubMed-indexed)

This animal and laboratory study examined how tirzepatide activates GIP and GLP-1 receptors, including experiments in insulin-producing pancreatic cells. Tirzepatide engaged GIP receptors more strongly and favored particular signals at GLP-1 receptors. These differences may enhance insulin release and help explain its promising effects on metabolism.

Citation: Willard FS, Douros JD, Gabe MB, Showalter AD, Wainscott DB, Suter TM, Capozzi ME, van der Velden WJ, Stutsman C, Cardona GR, Urva S, Emmerson PJ. Tirzepatide is an imbalanced and biased dual GIP and GLP-1 receptor agonist.. JCI insight 2020.

ClinicalTrials.gov · 2020 · NCT04537923 · ClinicalTrials.gov

This registered randomized human trial compared the safety and effectiveness of adding tirzepatide versus insulin lispro in people whose type 2 diabetes was inadequately controlled with insulin glargine, with or without metformin. The trial is listed as completed, but the supplied record reports no results.

Population / model

Type 2 Diabetes

Citation: Eli Lilly and Company. A Randomized, Phase 3, Open-label Trial Comparing the Effect of the Addition of Tirzepatide Once Weekly Versus Insulin Lispro (U100) Three Times Daily in Participants With Type 2 Diabetes Inadequately Controlled on Insulin Glargine (U100) With or Without Metformin (SURPASS-6). ClinicalTrials.gov 2020.

Molecular metabolism · 2018 · PMID 30473097 · BioNex Evolve (PubMed-indexed)

This study tested LY3298176 in lab cells, mice, and early randomized trials involving healthy people and adults with type 2 diabetes. It activated both GIP and GLP-1 receptors, improved glucose control in mice, and reduced fasting blood sugar and body weight in human trial comparisons with placebo. The most frequent side effects were digestive symptoms, considered mild to moderate.

Citation: Coskun T, Sloop KW, Loghin C, Alsina-Fernandez J, Urva S, Bokvist KB, Cui X, Briere DA, Cabrera O, Roell WC, Kuchibhotla U, Moyers JS. LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus: From discovery to clinical proof of concept.. Molecular metabolism 2018.

Lancet (London, England) · 2018 · PMID 30293770 · BioNex Evolve (PubMed-indexed)

This randomized phase 2 trial compared LY3298176, now known as tirzepatide, with placebo and dulaglutide in adults with poorly controlled type 2 diabetes. The provided results show greater reductions in HbA1c, a marker of long-term blood sugar, with LY3298176 than with placebo. The abstract is truncated, so complete comparative and safety results are not available here.

Citation: Frias JP, Nauck MA, Van J, Kutner ME, Cui X, Benson C, Urva S, Gimeno RE, Milicevic Z, Robins D, Haupt A. Efficacy and safety of LY3298176, a novel dual GIP and GLP-1 receptor agonist, in patients with type 2 diabetes: a randomised, placebo-controlled and active comparator-controlled phase 2 trial. Lancet (London, England) 2018.

ClinicalTrials.gov · 2018 · NCT03482024 · ClinicalTrials.gov

This registered human study examined how quickly tirzepatide enters the bloodstream and how long the body takes to remove it in people with impaired kidney function compared with healthy participants. The study is completed, but no results are provided in this record.

Population / model

Renal Insufficiency; End Stage Renal Disease

Citation: Eli Lilly and Company. Pharmacokinetics of Tirzepatide Following Administration to Subjects With Impaired Renal Function. ClinicalTrials.gov 2018.

2006 · PMID 35759552 · BioNex Evolve (PubMed-indexed)

The title identifies tirzepatide as the subject but provides no information about a study population or specific research question. The abstract was not available, so results are not summarized.

ISRCTN · ISRCTN10203365 · ISRCTN

The title describes a human trial investigating physical function during weight loss using several study groups in an open-label, adaptive design. The abstract was not available, so results are not summarized.

Citation: University of Leicester. Investigating and optimising physical function with weight loss: a multi-arm open-label adaptive platform trial. ISRCTN .

ISRCTN · ISRCTN11223313 · ISRCTN

The title describes an early-stage, randomized, placebo-controlled human trial of injected BC-006 in adults with obesity, examining safety, tolerability, how the drug behaves in the body, and preliminary effectiveness. The abstract was not available, so results are not summarized.

Citation: BaseCure Therapeutics Inc.. A Phase I, randomized, double-blind, placebo-controlled, single-dose study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of a subcutaneous injection of BC-006 in adults with obesity - part 1. ISRCTN .

ISRCTN · ISRCTN11609964 · ISRCTN

The title describes a human feasibility study of introducing a low-energy formula diet programme for weight loss within a kidney transplant service. The abstract was not available, so results are not summarized.

Citation: University College London. INFILTRATE: ImplemeNtation of a Formula low energy diet programme for weight loss In a renaL TRansplAnT sErvice Study - Work package 3 Feasibility Study. ISRCTN .

ISRCTN · ISRCTN13040627 · ISRCTN

The title concerns semaglutide use for elective weight loss in people without obesity and possible health benefits. The abstract was not available, so results are not summarized.

Citation: Sharon Giese, MD. Use of semaglutide for successful elective weight loss in a non-obese population and likely health benefits. ISRCTN .

ISRCTN · ISRCTN14812004 · ISRCTN

The title describes a randomized human trial in the UK examining the effectiveness and lasting health outcomes of a digital weight-loss programme supported by GLP-1 medication. The abstract was not available, so results are not summarized.

Citation: Eucalyptus. The effectiveness and sustainability of health outcomes from an advanced GLP-1-supported digital weight-loss programme in the UK: a randomized controlled trial. ISRCTN .

ISRCTN · ISRCTN14945909 · ISRCTN

This randomized human trial compares nutritional ketosis, a dietary approach that shifts the body toward using fat for fuel, with the NHS Eatwell guide in people with bipolar depression. The abstract was not available, so results are not summarized.

Citation: University of Edinburgh and NHS Lothian. Evaluating nutritional ketosis versus NHS Eatwell guide for bipolar depression: single blind randomised controlled trial. ISRCTN .

ISRCTN · ISRCTN17524311 · ISRCTN

The title describes a human feasibility study of a home-based approach to improving cardiovascular health in young people and their buddies. The abstract was not available, so results are not summarized.

Citation: King's College London. Prevent from home: young person and buddies’ cardiovascular health improvement feasibility study (PHYLLIS). ISRCTN .

ISRCTN · ISRCTN18176375 · ISRCTN

This early-stage, placebo-controlled human trial evaluates BC-006 injected under the skin in adults with obesity, examining safety, tolerability, how the drug behaves in the body, and early evidence of effectiveness. The abstract was not available, so results are not summarized.

Citation: BaseCure Therapeutics Inc.. A phase 1, randomized, double-blind, placebo-controlled, single-dose study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of a subcutaneous injection of BC-006 in adults with obesity- part 2. ISRCTN .

ISRCTN · ISRCTN22446424 · ISRCTN

The title describes a randomized trial examining the effects of tirzepatide-induced weight loss in adults with active idiopathic intracranial hypertension, a condition involving raised pressure around the brain. The abstract was not available, so results are not summarized.

Citation: University of Birmingham. A phase III multi-stage randomised controlled trial to determine the effects of weight loss, induced by Tirzepatide, in adults with active idiopathic intracranial hypertension. ISRCTN .

ISRCTN · ISRCTN83576037 · ISRCTN

This placebo-controlled human trial evaluates BC-006 combined with tirzepatide, injected under the skin, in adults with obesity, examining safety, tolerability, how the drugs behave in the body, and early evidence of effectiveness. The abstract was not available, so results are not summarized.

Citation: BaseCure Therapeutics Inc.. A Phase II, randomized, double-blind, placebo-controlled, combination therapy trial to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary efficacy of subcutaneous injections of BC-006 and tirzepatide in adults with obesity. ISRCTN .

International journal of molecular sciences · 2022 · PMID 36499281 · PubMed

This lab study examined how attaching sugars to proteins affects IGF-1 signaling in cultured Chinese hamster ovary cells. Cells with defective sugar attachment had fewer IGF-1 receptors and weaker activation of ERK signaling proteins after IGF-1 LR3 stimulation. The findings suggest that proper sugar attachment is essential for this signaling pathway.

Citation: Salvi R, Kumar C, Brahmbhatt K, Subedi R, Idicula-Thomas S, Madan T, Biswas B. N-Linked Glycosylation in Chinese Hamster Ovary Cells Is Critical for Insulin-like Growth Factor 1 Signaling.. International journal of molecular sciences 2022.

American journal of physiology. Endocrinology and metabolism · 2021 · PMID 33427051 · PubMed

This animal study examined LR3 IGF-1 in fetal sheep during late pregnancy. It increased heart, adrenal gland, and spleen weights without significantly changing overall fetal weight, placental blood flow, or fetal protein turnover. Amino acid transfer to the fetus decreased, leading the researchers to speculate that organ growth reflected efficient use of available nutrients rather than increased nutrient delivery.

Citation: Stremming J, Heard S, White A, Chang EI, Shaw SC, Wesolowski SR, Jonker SS, Rozance PJ, Brown LD. IGF-1 infusion to fetal sheep increases organ growth but not by stimulating nutrient transfer to the fetus.. American journal of physiology. Endocrinology and metabolism 2021.

American journal of physiology. Endocrinology and metabolism · 2021 · PMID 33938236 · PubMed

This animal and lab study examined IGF-1 LR3 in fetal sheep during late pregnancy and in pancreatic islets isolated from them. IGF-1 LR3 lowered circulating insulin and glucose and reduced insulin release in response to glucose. Reduced insulin release persisted in isolated islets, indicating a defect within the insulin-producing tissue itself.

Citation: White A, Stremming J, Boehmer BH, Chang EI, Jonker SS, Wesolowski SR, Brown LD, Rozance PJ. Reduced glucose-stimulated insulin secretion following a 1-wk IGF-1 infusion in late gestation fetal sheep is due to an intrinsic islet defect.. American journal of physiology. Endocrinology and metabolism 2021.

FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020 · PMID 32573852 · PubMed

This animal study examined whether blood vessels supplying the heart kept pace with IGF-1 LR3-stimulated heart growth in fetal sheep. Heart growth was accompanied by appropriate growth and function of these vessels, with similar blood-flow responses to low oxygen in treated and control animals.

Citation: Jonker SS, Giraud GD, Chang EI, Elman MR, Louey S. Coronary vascular growth matches IGF-1-stimulated cardiac growth in fetal sheep.. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2020.

Scientific reports · 2019 · PMID 31285507 · PubMed

This laboratory and animal study tested ALK4/5 blockers and IGF-I LR3 in muscle cells and mice with cancer-related muscle wasting. GW788388 was more effective than SB431542 at limiting losses in body weight, grip strength, and muscle weight. IGF-I LR3 limited muscle loss but also accelerated tumor growth.

Citation: Levolger S, Wiemer EAC, van Vugt JLA, Huisman SA, van Vledder MG, van Damme-van Engel S, Ambagtsheer G, IJzermans JNM, de Bruin RWF. Inhibition of activin-like kinase 4/5 attenuates cancer cachexia associated muscle wasting.. Scientific reports 2019.

The Journal of endocrinology · 2008 · PMID 18577570 · PubMed

This animal study compared growth hormone, prolactin, and IGF-I LR3 in mice during prolonged lactation. Growth hormone increased lactation capacity, measured through offspring weight gain, while IGF-I LR3 produced a modest increase and prolactin did not. IGF-I LR3 also increased mammary Akt signaling and activity of the SOCS3 gene.

Citation: Hadsell DL, Parlow AF, Torres D, George J, Olea W. Enhancement of maternal lactation performance during prolonged lactation in the mouse by mouse GH and long-R3-IGF-I is linked to changes in mammary signaling and gene expression.. The Journal of endocrinology 2008.

The British journal of nutrition · 2002 · PMID 12067429 · PubMed

This animal study tested IGF-I and LR3 IGF-I in artificially reared newborn pigs under restricted or unrestricted milk feeding. Neither peptide improved weight gain with restricted feeding. With unrestricted feeding, LR3 IGF-I increased weight gain during the later study period, while both growth factors increased milk intake.

Citation: Dunshea FR, Chung CS, Owens PC, Ballard JF, Walton PE. Insulin-like growth factor-I and analogues increase growth in artificially-reared neonatal pigs.. The British journal of nutrition 2002.

The Journal of endocrinology · 1997 · PMID 9488001 · PubMed

This animal study examined IGF-I and its LR3 analogue, alone or with growth hormone, in pigs nearing market weight. LR3 IGF-I reduced weight gain, food intake, and several circulating hormones and binding proteins; ordinary IGF-I did not change weight gain or food intake. Both peptides suppressed growth hormone, which may contribute to LR3 IGF-I's growth-inhibiting effects.

Citation: Dunaiski V, Dunshea FR, Walton PE, Goddard C. Long [R3] insulin-like growth factor-I reduces growth, plasma growth hormone, IGF binding protein-3 and endogenous IGF-I concentrations in pigs.. The Journal of endocrinology 1997.

The Journal of endocrinology · 1995 · PMID 7561636 · PubMed

This animal study compared IGF-I, IGF-II, and LR3 IGF-I infusions in female guinea pigs. LR3 IGF-I increased the weights of the adrenal glands, gut, kidneys, and spleen relative to body weight, but did not stimulate overall growth. None of the treatments significantly changed body weight gain, food intake, feed efficiency, or body composition.

Citation: Conlon MA, Tomas FM, Owens PC, Wallace JC, Howarth GS, Ballard FJ. Long R3 insulin-like growth factor-I (IGF-I) infusion stimulates organ growth but reduces plasma IGF-I, IGF-II and IGF binding protein concentrations in the guinea pig.. The Journal of endocrinology 1995.

Gut · 1995 · PMID 8549937 · PubMed

This animal study compared short-term effects of IGF-I and LR3 IGF-I on intestinal growth in female rats. Both peptides increased markers of cell division in the small intestine, but only LR3 IGF-I increased body weight, intestinal weight, and the size of intestinal cell-producing structures. The findings suggest that intestinal cell proliferation advanced more rapidly with LR3 IGF-I.

Citation: Steeb CB, Trahair JF, Read LC. Administration of insulin-like growth factor-I (IGF-I) peptides for three days stimulates proliferation of the small intestinal epithelium in rats.. Gut 1995.

International immunopharmacology · 2025 · PMID 39954662 · PubMed

This review examined LL-37 in human periodontitis, a disease affecting the tissues supporting teeth. Studies reported higher LL-37 levels in fluid around the gums of patients with periodontitis than in healthy people. The review describes antimicrobial, immune-regulating, and tissue-repair effects, while identifying potential treatments and disease markers as areas for future research.

Citation: He Y, Zhou Y, Liu N, Zhang W, Chen X, Qiu G, Shen Y. Cathelicidin LL-37 in periodontitis: current research advances and future prospects - A review.. International immunopharmacology 2025.

International journal of molecular sciences · 2025 · PMID 40869425 · PubMed

This review examines modifications to the human antimicrobial peptide LL-37, rather than reporting a new human trial. It describes modified forms that preserve or improve biological activity while reducing toxicity and resisting breakdown by enzymes. Their therapeutic potential remains promising, but long-term safety and effectiveness require further validation.

Citation: Voronko OE, Khotina VA, Kashirskikh DA, Lee AA, Gasanov VAO. Antimicrobial Peptides of the Cathelicidin Family: Focus on LL-37 and Its Modifications.. International journal of molecular sciences 2025.

Biophysical journal · 2024 · PMID 37919905 · PubMed

This review examines research on the human immune peptide LL-37 binding to nucleic acids and affecting innate immunity; the abstract does not specify the study populations or experimental models. These complexes have shown beneficial immune-stimulating effects, but some studies suggest they may also contribute to autoimmune disorders such as psoriasis and lupus.

Citation: Zielke C, Nielsen JE, Lin JS, Barron AE. Between good and evil: Complexation of the human cathelicidin LL-37 with nucleic acids.. Biophysical journal 2024.

World journal of microbiology & biotechnology · 2023 · PMID 38057654 · PubMed

This review summarizes research on LL-37 against fungi relevant to human disease and agriculture, rather than reporting a human treatment trial. LL-37 can inhibit fungal growth through mechanisms including damage to cell walls and membranes and disruption of internal cell processes. Evidence also suggests it may reduce fungi's ability to cause disease.

Citation: Memariani M, Memariani H. Antifungal properties of cathelicidin LL-37: current knowledge and future research directions.. World journal of microbiology & biotechnology 2023.

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2023 · PMID 36958193 · PubMed

This animal and lab study tested LL-37 in rats with heat stroke and cultured intestinal cells. LL-37 reduced intestinal injury and systemic inflammation, improved organ function, and increased survival in the rats. The researchers linked these effects to protection of mucus-producing intestinal cells and improved intestinal barrier function.

Citation: Shih CC, Liao WC, Ke HY, Kuo CW, Tsao CM, Tsai WC, Chiu YL, Huang HC, Wu CC. Antimicrobial peptide cathelicidin LL-37 preserves intestinal barrier and organ function in rats with heat stroke.. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 2023.

World journal of microbiology & biotechnology · 2023 · PMID 36781570 · PubMed

This review examines research on LL-37 against bacterial biofilms, communities of bacteria embedded in a protective layer. Evidence suggests LL-37 can prevent biofilm establishment through effects on bacterial attachment, signaling, and the protective layer. Its effectiveness and safety in living organisms remain uncertain.

Citation: Memariani H, Memariani M. Antibiofilm properties of cathelicidin LL-37: an in-depth review.. World journal of microbiology & biotechnology 2023.

ClinicalTrials.gov · 2023 · NCT06219330 · ClinicalTrials.gov

This completed human case-control study examined salivary LL-37 in patients with potentially malignant oral lesions and healthy controls. The abstract reports strong diagnostic accuracy in distinguishing these groups and suggests LL-37 could serve as a noninvasive marker for early detection.

Population / model

Oral Potentially Malignant Lesions

Citation: Fayoum University. "Salivary Levels of Cathelicidin LL-37 in Patients With Oral Potentially Malignant Lesions, A Case Control Study". ClinicalTrials.gov 2023.

Biomedicines · 2022 · PMID 35625823 · PubMed

This review examined the human peptide LL-37 in oral health and disease. It described antimicrobial and immune-regulating roles that help maintain oral microbial balance, alongside involvement in microbial imbalance, infections, autoimmune diseases, and oral cancers. LL-37 has also been proposed as a marker of inflammation severity and treatment outcomes.

Citation: Tokajuk J, Deptuła P, Piktel E, Daniluk T, Chmielewska S, Wollny T, Wolak P, Fiedoruk K, Bucki R. Cathelicidin LL-37 in Health and Diseases of the Oral Cavity.. Biomedicines 2022.

ClinicalTrials.gov · 2021 · NCT06867250 · ClinicalTrials.gov

This completed human observational study examined vitamin D and LL-37 in fluid around dental implants, focusing on immune defenses and inflammation in healthy and diseased surrounding tissues. The abstract describes the study aims but reports no results.

Population / model

Peri-Implantitis and Peri-implant Mucositis

Citation: Altinbas University. Evaluation of Peri-Implant Sulcus Fluid Vitamin D and Cathelicidin (LL-37) Levels in Peri-Implant Health and Diseases. ClinicalTrials.gov 2021.

ClinicalTrials.gov · 2021 · NCT04404335 · ClinicalTrials.gov

This registered human observational study examined LL-37 and immune-related proteins in fluid between the gums and teeth in people with and without gum disease, including changes after periodontal treatment. The study is marked completed, but the record provides no results.

Population / model

Periodontal Diseases; Periodontitis

Citation: Universidad Rey Juan Carlos. The Role of Anti-inflammatory Cytokines and Antimicrobial Peptide LL-37 Biomarkers in the Treatment of Periodontal Disease.. ClinicalTrials.gov 2021.

ClinicalTrials.gov · 2021 · NCT04861493 · ClinicalTrials.gov

This completed human observational study examined LL-37 levels in saliva and fluid around the gums in smokers and non-smokers with advanced periodontitis. The supplied abstract provides background on gum disease and smoking but reports no study results.

Population / model

Smoking Reduction

Citation: Cairo University. Cathelicidin LL-37 Levels in the Gingival Crevicular Fluid and the Saliva of Smokers and Non-smokers With Stage III,IV Periodontitis :An Observational Study. ClinicalTrials.gov 2021.

BioMed research international · 2020 · PMID 32509872 · PubMed

This review examines research on the human immune peptide LL-37 in different tissues and local environments. It describes contrasting roles: LL-37 can promote inflammation and anti-infection or antitumor responses, but can also inhibit inflammation and promote cancer development. Its effects depend on the tissue and surrounding conditions.

Citation: Yang B, Good D, Mosaiab T, Liu W, Ni G, Kaur J, Liu X, Jessop C, Yang L, Fadhil R, Yi Z, Wei MQ. Significance of LL-37 on Immunomodulation and Disease Outcome.. BioMed research international 2020.

ClinicalTrials.gov · 2019 · NCT04098562 · ClinicalTrials.gov

This registered randomized human trial planned to compare LL-37 cream with placebo alongside standard wound care for diabetic foot ulcers. It aimed to assess wound healing, bacteria, and inflammatory markers. The study status is unknown, and the abstract reports no results.

Population / model

Diabetic Foot Ulcer

Citation: Fakultas Kedokteran Universitas Indonesia. The Efficacy of LL-37 Cream on Aerobic Bacteria Colonization Pattern, Inflammation Response: Interleukin 1α (IL-1α) and Tumor Necrosis Factor α (TNF-α), and Healing Rate of Diabetic Foot Ulcers. ClinicalTrials.gov 2019.

Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology · 2018 · PMID 29843147 · PubMed

This review examines LL-37's roles in human cancers, including laboratory research on cancer cells. It reports cancer-promoting effects in some cancer types and anticancer effects in others. Differences in cell-surface receptors and signaling pathways appear to help explain these tissue-specific effects.

Citation: Chen X, Zou X, Qi G, Tang Y, Guo Y, Si J, Liang L. Roles and Mechanisms of Human Cathelicidin LL-37 in Cancer.. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 2018.

ClinicalTrials.gov · 2018 · NCT03270709 · ClinicalTrials.gov

This registered human trial planned to examine vitamin D supplementation, lung immune-cell function, LL-37, and oxidative stress in smokers and non-smokers with and without HIV. Its goal was to investigate immune defenses against infection. The trial is listed as terminated, and the supplied abstract reports no trial results.

Population / model

HIV/AIDS; Vitamin D Deficiency; Smoker Lung

Citation: Emory University. Effect of High-Dose Vitamin D3 on Alveolar Macrophage Function, LL-37, and Oxidative Stress in Smokers and Non-Smokers With and Without HIV. ClinicalTrials.gov 2018.

Biochimica et biophysica acta · 2016 · PMID 26556394 · PubMed

This review examines how LL-37’s structure relates to its effects on bacteria and human cells. It describes LL-37 forming pores in bacterial membranes and influencing immune responses, inflammation, blood vessel growth, and wound healing. Its reported functions include both increasing inflammation to fight infection and limiting inflammation to reduce tissue damage.

Citation: Xhindoli D, Pacor S, Benincasa M, Scocchi M, Gennaro R, Tossi A. The human cathelicidin LL-37--A pore-forming antibacterial peptide and host-cell modulator.. Biochimica et biophysica acta 2016.

ClinicalTrials.gov · 2016 · NCT02806414 · ClinicalTrials.gov

This registered human trial examined topical ivermectin in people with rosacea, focusing on enzyme activity, the antimicrobial peptide LL-37, and microorganisms living on the skin. Researchers planned to assess whether changes in these measures correlated with disease severity. The trial is listed as completed, but the supplied abstract reports no results.

Population / model

Rosacea

Citation: University of California, San Diego. A Single Site Evaluation of the Inhibitory Effects of Topical Ivermectin on Serine Protease Activity and Production of LL-37 Cathelicidin Peptide, Biochemical Markers of Rosacea-specific Inflammation and on the Skin Microbiome in Rosacea.. ClinicalTrials.gov 2016.

Frontiers in oncology · 2015 · PMID 26175965 · PubMed

This review examines LL-37 and related peptides in cancer research, including laboratory studies in cancer cell lines. Previous studies suggest LL-37 can contribute to cancer development, while LL-37 and its fragments and analogs also show anticancer effects in cancer cells. These contrasting effects depend on peptide properties, cell membranes, and cellular signaling.

Citation: Kuroda K, Okumura K, Isogai H, Isogai E. The Human Cathelicidin Antimicrobial Peptide LL-37 and Mimics are Potential Anticancer Drugs.. Frontiers in oncology 2015.

ClinicalTrials.gov · 2015 · NCT02225366 · ClinicalTrials.gov

This registered clinical trial in people with melanoma aimed to investigate LL-37 and whether it could stimulate the immune system to help control the disease. The trial is listed as completed, but the supplied abstract reports no results.

Population / model

Melanoma

Citation: M.D. Anderson Cancer Center. Induction of Antitumor Response in Melanoma Patients Using the Antimicrobial Peptide LL37. ClinicalTrials.gov 2015.

ClinicalTrials.gov · 2011 · NCT01398280 · ClinicalTrials.gov

This completed human trial studied whether topical aminocaproic acid affects antimicrobial peptides, including LL-37, in the skin of patients with rosacea. The abstract proposes that it may inhibit peptide activation but reports no results.

Population / model

Rosacea

Citation: University of California, San Diego. A Single Site Evaluation of the Effect of Topical Application of Aminocaproic Acid (ACA) to Inhibit Kallikrein 5 Serine Protease Activity and Production of LL-37 Cathelicidin Peptide, Biochemical Markers of Rosacea-specific Inflammation.. ClinicalTrials.gov 2011.

ClinicalTrials.gov · 2008 · NCT00788320 · ClinicalTrials.gov

This registered human trial planned to examine vitamin D supplementation and the relationship between vitamin D levels and LL-37 in blood and sputum from patients with active lung tuberculosis. The trial was withdrawn, and no study results are reported.

Population / model

Tuberculosis

Citation: Atlanta VA Medical Center. Antimicrobial Peptide LL-37 (Cathelicidin) Production in Active Tuberculosis Disease: Role of Vitamin D Supplementation. ClinicalTrials.gov 2008.

European journal of pharmacology · 2026 · PMID 42633878 · BioNex Evolve (PubMed-indexed)

This review examines whether MOTS-c could be relevant to heart muscle dysfunction caused by sepsis, drawing partly on research in other disease models. Studies link MOTS-c to processes involving energy regulation, inflammation, and cell protection, but direct evidence in sepsis-related heart dysfunction is limited. Its potential as a biological marker or treatment candidate remains insufficiently validated.

Citation: Zhao Z, Chen W, Zheng X, Geng Z, Dai N, Zhang H, Fu B, Fu X. MOTS-c in sepsis-induced cardiomyopathy: Mechanisms and translational potential. European journal of pharmacology 2026.

Experimental physiology · 2026 · PMID 42321010 · BioNex Evolve (PubMed-indexed)

This animal study tested MOTS-c in rats with experimentally induced type 2 diabetes. MOTS-c significantly reduced fasting blood sugar and circulating C-reactive protein, an inflammation marker, and reduced markers of an inflammation-activating protein complex in heart tissue. These results concern rats, not demonstrated cardiovascular benefits in humans.

Citation: Mills AR, de Souza A, Pham T, Mugisho OO. Mitochondrial peptide MOTS-c suppresses systemic and cardiac inflammasome activation in a diabetic rat model. Experimental physiology 2026.

Journal of translational medicine · 2026 · PMID 42243958 · BioNex Evolve (PubMed-indexed)

This review examined MOTS-c in respiratory diseases using human studies and preclinical laboratory and animal research. Available studies suggest lower circulating MOTS-c in acute respiratory distress and chronic respiratory diseases, while administered MOTS-c reduced lung injury in preclinical models. Further clinical studies are needed to establish whether it can affect disease progression or outcomes in people.

Citation: Amado CA, Agüero J, García-Unzueta M, Berja A, Lavín BA, Martín-Audera P. MOTS-c: How a secreted mitochondrial microprotein may become a potential treatment for inflammatory lung diseases. Journal of translational medicine 2026.

Life sciences · 2026 · PMID 42128272 · BioNex Evolve (PubMed-indexed)

This animal and lab study tested MOTS-c in newborn mice and rat heart cells exposed to excessive oxygen. MOTS-c reduced heart enlargement, scarring, and dysfunction in mice and inhibited oxidative stress-related cell death. The findings suggest that MOTS-c could interact with KEAP1 to maintain its interaction with PGAM5, helping limit this cell-death pathway.

Citation: Li SH, Chen SQ, Lu T, Wang JH, Wang JX, Wu YX, Pang QF, Chen D. MOTS-c attenuates hyperoxia-induced neonatal cardiac injury by inhibiting oxeiptosis via maintaining the KEAP1-PGAM5 interaction. Life sciences 2026.

Folia histochemica et cytobiologica · 2026 · PMID 41811086 · BioNex Evolve (PubMed-indexed)

This animal study examined how MOTS-c affects adrenal glands in adult male rats. MOTS-c changed metabolic and cell-signaling pathways without changing key hormone-production genes or circulating corticosterone and aldosterone. The researchers concluded that it prepares adrenal cells for later stimulation rather than directly increasing baseline hormone production.

Citation: Blatkiewicz M, Kaminski K, Sobalska-Kwapis M, Szyszka M, Olechnowicz A, Jopek K, Rucinski M. MOTS-c primes adrenal cortex metabolism without directly driving steroidogenesis. Folia histochemica et cytobiologica 2026.

Molecular biology reports · 2026 · PMID 42228044 · BioNex Evolve (PubMed-indexed)

This lab study used isolated female rat hearts to examine injury caused by stopping and restoring blood flow. MOTS-c was associated with improved recovery of heart function, reduced oxidative stress, and partial preservation of mitochondrial function and DNA. The researchers noted that the underlying signaling mechanisms need further validation.

Citation: Santhanam SS, Jayaraman S, Rajesh SS, Iyer VNH, Kurian GA. MOTS-c preserves mitochondrial subpopulation bioenergetics and genome integrity to attenuate cardiac ischemia reperfusion injury. Molecular biology reports 2026.

Protein and peptide letters · 2026 · PMID 41764620 · BioNex Evolve (PubMed-indexed)

This animal study tested MOTS-c in male mice with acetaminophen-induced liver injury. MOTS-c reduced liver damage, markers of liver injury, inflammation, oxidative stress, and liver cell death. The researchers linked these protective effects to suppression of the MAPK signaling pathway.

Citation: Li N, Xu Y, Chen Q, Jiang J, Li WW. MOTS-c Protects Against Acetaminophen-induced Liver Injury through the MAPK Signaling Pathway. Protein and peptide letters 2026.

Molecular neurobiology · 2026 · PMID 41706383 · BioNex Evolve (PubMed-indexed)

This animal study tested MOTS-c in a valproic acid-induced rat model of autism. MOTS-c reversed impaired sociability, repetitive behaviors, cerebellar cell loss, and increased oxidative stress, but not anxiety or neocortical damage. Blood levels of tetrahydrobiopterin and brain-derived neurotrophic factor did not significantly change, suggesting the observed benefits were independent of changes in these factors.

Citation: Güvenir Seven S, Sahin H, Erkanlı Şentürk G, Uysal N, Uzun H, Ekici O, Rakıcı G, Şimşek G. Therapeutic Effects of MOTS-c in the Valproic Acid-Induced Autism Model in Rats: Role of Tetrahydrobiopterin and Brain-Derived Neurotrophic Factor. Molecular neurobiology 2026.

Naunyn-Schmiedeberg's archives of pharmacology · 2026 · PMID 41593376 · BioNex Evolve (PubMed-indexed)

This animal laboratory study tested MOTS-c in isolated rat hearts injured by interrupted and restored blood flow, with supporting computer modeling. MOTS-c reduced heart tissue damage, improved heart function, and strengthened antioxidant defenses while reducing markers of inflammation and cell death. The isolated-heart findings require further research before application to humans.

Citation: Santhanam SS, Jayaraman S, Kurian GA. Exogenous MOTS-c mitigates myocardial ischemia-reperfusion injury: experimental and in silico evidence from rat heart models. Naunyn-Schmiedeberg's archives of pharmacology 2026.

The International journal of neuroscience · 2026 · PMID 40753494 · BioNex Evolve (PubMed-indexed)

This animal study tested MOTS-c in mice with experimentally induced sepsis. MOTS-c improved survival, reduced brain injury and inflammation, and reduced leakage through the blood-brain barrier, which helps protect the brain.

Citation: Bai Y, Wu H, Wang X, Guo Y, Gong B, Dong B, Yu Y. A mitochondrial-derived peptide MOTS-c contributes to the protective effect against brain injury associated with LPS-induced sepsis by strengthening the blood-brain barrier's ultrastructure. The International journal of neuroscience 2026.

ClinicalTrials.gov · 2026 · NCT07505745 · ClinicalTrials.gov

This recruiting human trial is testing whether investigational MOTS-c improves the body’s response to insulin compared with placebo in adults with prediabetes and overweight or obesity. Safety is also being monitored; no results are reported.

Population / model

Prediabetes; Insulin Resistance; Overweight/Obesity

Citation: Hudson Biotech. A Phase 2a, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy, Safety, and Pharmacodynamics of MOTS-c (a Mitochondrial-Derived Peptide) in Adults With Prediabetes and Overweight/Obesity. ClinicalTrials.gov 2026.

ClinicalTrials.gov · 2026 · NCT07678073 · ClinicalTrials.gov

This human trial compares general anesthesia with combined spinal-epidural anesthesia in adult kidney transplant recipients. It will measure markers of iron-related cell death, humanin and MOTS-c levels, and early transplant outcomes. The trial is recruiting, and no results are reported.

Population / model

Kidney Disease, End-Stage; Kidney Transplant; Kidney; Kidney Disease; Renal Transplant

Citation: University of Gaziantep. Comparison of the Effects of General Anesthesia and Combined Spinal-Epidural Anesthesia on Ferroptosis, Humanin and MOTS-c Levels in Renal Transplantation: A Prospective Controlled Study. ClinicalTrials.gov 2026.

Redox Biology · 2025 · PMID 40403491 · BioNex Evolve (PubMed-indexed)

This animal and lab study examined MOTS-c in lung injury caused by interrupted and restored blood flow, alongside human observations after heart-lung bypass. In rats, MOTS-c reduced oxidative damage, inflammation, lung injury, and mortality by activating antioxidant defenses. In patients, changes in blood MOTS-c levels predicted acute respiratory distress syndrome better than traditional biomarkers.

Citation: Li X, Zhan F, Qiu G, Lu P, Shen Z, Qi Y. MOTS-c attenuates lung ischemia-reperfusion injury via MYH9-dependent nuclear translocation and transcriptional activation of antioxidant genes.. Redox Biology 2025.

Cardiovascular drugs and therapy · 2025 · PMID 40172798 · BioNex Evolve (PubMed-indexed)

The title considers MOTS-c as a possible candidate for diabetes-related heart muscle disease. The abstract was not available, so results are not summarized.

Citation: Yerra VG, Connelly KA. MOTS-c: Magical Molecule for Diabetic Cardiomyopathy?. Cardiovascular drugs and therapy 2025.

Life sciences · 2025 · PMID 41083123 · BioNex Evolve (PubMed-indexed)

This review examines MOTS-c in relation to type 2 diabetes risk factors and complications, including preclinical studies of metabolic disease. Emerging evidence suggests that insufficient MOTS-c production may contribute to diabetes and its complications. The review explores its potential to protect against diabetes-related heart muscle disease, rather than establishing effectiveness in humans.

Citation: Fang T, Han JC, Taberner A, Pham T. MOTS-c in type 2 diabetes mellitus: From risk factors to cardiac complications and potential treatment. Life sciences 2025.

Histochemistry and cell biology · 2025 · PMID 40478460 · BioNex Evolve (PubMed-indexed)

This lab study examined MOTS-c in pancreatic islets, clusters of hormone-producing cells isolated from rats and pigs. MOTS-c affected islet function, including reducing insulin and glucagon release and improving cell survival. Its effects differed between the species.

Citation: Bień J, Pruszynska-Oszmalek E, Kolodziejski P, Leciejewska N, Szczepankiewicz D, Grzęda E, Sassek M. MOTS-c modulates pancreatic islet function in rats and pigs in vitro. Histochemistry and cell biology 2025.

Journal of muscle research and cell motility · 2025 · PMID 40608240 · BioNex Evolve (PubMed-indexed)

This animal study examined MOTS-c in male rats whose hindlimbs were suspended to prevent normal weight-bearing. MOTS-c prevented increased calf muscle fatigue and the shift from slow to fast muscle fibers, while reducing shrinkage of slow fibers but not fast fibers. It also supported processes involved in protein balance and mitochondrial maintenance.

Citation: Sidorenko DA, Lvova ID, Tyganov SA, Shenkman BS, Sharlo KA. The impact of mitokine MOTS-c administration on the soleus muscle of rats subjected to a 7-day hindlimb suspension. Journal of muscle research and cell motility 2025.

Scientific reports · 2025 · PMID 40425777 · BioNex Evolve (PubMed-indexed)

This animal and lab study examined MOTS-c and aerobic exercise in rats with type 2 diabetes and liver scarring, alongside experiments in cultured cells. Both MOTS-c and exercise improved liver scarring in rats. Cell experiments showed that MOTS-c reduced reactive oxygen molecules and changed antioxidant and scarring-related signals, supporting a role for the Keap1-Nrf2-Smad2/3 pathway.

Citation: Chen F, Li Z, Wang T, Fu Y, Lyu L, Xing C, Li S, Li. MOTS-c mimics exercise to combat diabetic liver fibrosis by targeting Keap1-Nrf2-Smad2/3. Scientific reports 2025.

Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology · 2025 · PMID 39876762 · BioNex Evolve (PubMed-indexed)

This lab study tested MOTS-c in two muscle cell lines representing different muscle fiber types. MOTS-c increased survival and promoted development into specialized muscle cells in C2C12 cells but not L6 cells, while slowing proliferation in both. Fat accumulation decreased in C2C12 cells and increased in L6 cells, suggesting responses depend on muscle cell type.

Citation: Leciejewska N, Pruszyńska-Oszmałek E, Kołodziejski P, Szczepankiewicz D, Nogowski L, Sassek M. MOTS-c Impact on Muscle Cell Differentiation and Metabolism Across Fiber Types. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 2025.

Medicine and science in sports and exercise · 2025 · PMID 40674654 · BioNex Evolve (PubMed-indexed)

This human trial compared repeated heat exposure with sham treatment in physically active men whose ankle was immobilized. Heat exposure increased circulating MOTS-c and decreased FGF21 in skeletal muscle, while immobilization itself did not change these signals. Immobilization reduced calf muscle size; the abstract does not establish that heat exposure prevented this loss.

Citation: Elhusseiny R, Ihsan M, Labidi M, Alhammoud M, Mtibaa K, Nader N, Nasir N, Farooq A, Papakostas E, Olory B, Cruz F, D'Hooghe P, Racinais S, Deldicque L. Repeated Heat Stress Modulates the Levels of the Mitokines MOTS-C and FGF21 in Active Men during Calf Muscle Immobilization. Medicine and science in sports and exercise 2025.

Cardiovascular drugs and therapy · 2025 · PMID 38141139 · BioNex Evolve (PubMed-indexed)

This animal study tested MOTS-c in mice with type 1 diabetes and diabetes-related heart damage. MOTS-c improved heart function and structural abnormalities, restored AMPK signaling, and reduced heart inflammation. The researchers suggested that its protective effects may involve AMPK activation and reduced inflammation.

Citation: Wu N, Shen C, Wang J, Chen X, Zhong P. MOTS-c Peptide Attenuated Diabetic Cardiomyopathy in STZ-Induced Type 1 Diabetic Mouse Model. Cardiovascular drugs and therapy 2025.

Advanced Science · 2024 · PMID 39321430 · BioNex Evolve (PubMed-indexed)

This lab and animal study examined MOTS-c in ovarian cancer and also analyzed patient blood and tumor samples. Lower MOTS-c levels in patients were associated with poorer prognosis. MOTS-c inhibited cancer cell growth and movement, promoted cancer cell death, and reduced tumor growth in animals without systemic toxicity.

Citation: Yin Y, Li Y, Ma B, Ren C, Zhao S, Li J. Mitochondrial-Derived Peptide MOTS-c Suppresses Ovarian Cancer Progression by Attenuating USP7-Mediated LARS1 Deubiquitination.. Advanced Science 2024.

iScience · 2024 · PMID 39559755 · BioNex Evolve (PubMed-indexed)

This laboratory, mouse, and human genetic study examined how MOTS-c affects muscle through the enzyme CK2. MOTS-c directly activated CK2 in cell-free tests and prevented muscle wasting and increased muscle glucose uptake in mice; suppressing CK2 weakened these effects. A less-active MOTS-c variant was associated with differing risks of muscle loss and type 2 diabetes depending on sex, age, and activity.

Citation: Kumagai H, Kim SJ, Miller B, Zempo H, Tanisawa K, Natsume T, Lee SH, Wan J, Leelaprachakul N, Kumagai ME, Ramirez R, Mehta HH. MOTS-c modulates skeletal muscle function by directly binding and activating CK2.. iScience 2024.

American journal of physiology. Endocrinology and metabolism · 2024 · PMID 38170165 · BioNex Evolve (PubMed-indexed)

This animal study examined MOTS-c in male mice with muscle wasting caused by immobilization. MOTS-c reduced muscle loss, fat buildup within muscle, and circulating inflammatory signals. The findings suggest that regulation of fat-related genes and muscle signaling pathways contributes to these effects.

Citation: Kumagai H, Kim SJ, Miller B, Natsume T, Wan J, Kumagai ME, Ramirez R, Lee SH, Sato A, Mehta HH, Yen K, Cohen P. Mitochondrial-derived microprotein MOTS-c attenuates immobilization-induced skeletal muscle atrophy by suppressing lipid infiltration.. American journal of physiology. Endocrinology and metabolism 2024.

Gut · 2024 · PMID 37788894 · BioNex Evolve (PubMed-indexed)

This study measured MOTS-c in people with and without hepatitis B and tested its effects in infected mice and cells. Higher MOTS-c levels were associated with lower viral DNA levels in humans. In animal and laboratory experiments, MOTS-c inhibited viral replication and improved liver function without notable toxicity, with effects linked to mitochondrial regulation and antiviral signaling.

Citation: Lin C, Luo L, Xun Z, Zhu C, Huang Y, Ye Y, Zhang J, Chen T, Wu S, Zhan F, Yang B, Liu C. Novel function of MOTS-c in mitochondrial remodelling contributes to its antiviral role during HBV infection.. Gut 2024.

Biochemical and biophysical research communications · 2024 · PMID 39616938 · BioNex Evolve (PubMed-indexed)

This animal study examined the effects of MOTS-c on heart structure and inflammation in rats with diabetes. MOTS-c reduced proteins involved in the ROS/TXNIP/NLRP3 pathway and suppressed heart inflammation. The findings suggested that blocking this pathway helps MOTS-c reduce diabetes-related heart muscle damage.

Citation: Fu Y, Tang M, Duan Y, Pan Y, Liang M, Yuan J, Wang M, Laher I, Li S. MOTS-c regulates the ROS/TXNIP/NLRP3 pathway to alleviate diabetic cardiomyopathy. Biochemical and biophysical research communications 2024.

Drug design, development and therapy · 2024 · PMID 39050800 · BioNex Evolve (PubMed-indexed)

This animal study examined MOTS-c in male mice with traumatic brain injury. MOTS-c improved learning, memory, and movement while reducing inflammation, molecular damage, and cell death. Analyses also identified changes in signaling and energy metabolism linked to these effects.

Citation: Li F, Jia Y, Fang J, Gong L, Zhang Y, Wei S, Wu L, Jiang P. Neuroprotective Mechanism of MOTS-c in TBI Mice: Insights from Integrated Transcriptomic and Metabolomic Analyses. Drug design, development and therapy 2024.

Histochemistry and cell biology · 2024 · PMID 38430258 · BioNex Evolve (PubMed-indexed)

This lab study examined MOTS-c in cultured pancreatic alpha and beta cell lines, rather than in humans or whole animals. MOTS-c lowered insulin production and release in beta cells while increasing glucagon production and release in alpha cells. It also affected cell survival and programmed cell death.

Citation: Bień J, Pruszyńska-Oszmałek E, Kołodziejski P, Leciejewska N, Szczepankiewicz D, Sassek M. MOTS-c regulates pancreatic alpha and beta cell functions in vitro. Histochemistry and cell biology 2024.

Neuroscience letters · 2024 · PMID 38462167 · BioNex Evolve (PubMed-indexed)

This animal study examined MOTS-c infused into the brain in male rats with and without obesity. MOTS-c increased brain production of the reproductive signal GnRH and blood levels of testosterone, LH, and FSH, with stronger hormone increases in rats without obesity. These findings suggest that MOTS-c may stimulate the reproductive hormone system.

Citation: Ozturk Öztürk DA, Erden Y, Tekin S. Central MOTS-c infusion affects reproductive hormones in obese and non-obese rats. Neuroscience letters 2024.

Reproductive toxicology (Elmsford, N.Y.) · 2024 · PMID 39079574 · BioNex Evolve (PubMed-indexed)

This animal study examined MOTS-c and a Humanin analog in male mice exposed to cyclophosphamide chemotherapy before puberty. Both peptides protected sperm-producing function against reproductive injury, and researchers identified changes in genes related to male reproductive function.

Citation: Wang J, Wen W, Liu L, He J, Deng R, Su M, Zhao S, Wang H, Rao M, Tang L. Effect of Humanin and MOTS-c on ameliorating reproductive damage induced by prepubertal cyclophosphamide chemotherapy in male mice. Reproductive toxicology (Elmsford, N.Y.) 2024.

Blood purification · 2024 · PMID 39111290 · BioNex Evolve (PubMed-indexed)

This observational human study examined blood MOTS-c levels as a risk marker in people receiving long-term hemodialysis. Higher levels were independently associated with the combined outcome of death or nonfatal cardiovascular events, and adding MOTS-c improved prediction models. Larger, more varied studies are needed to confirm how broadly these findings apply.

Citation: Bolignano D, Greco M, Presta P, Duni A, Zicarelli M, Mercuri S, Pappas E, Lakkas L, Musolino M, Naka KK, Misiti R, Foti DP, Andreucci M, Coppolino G, Dounousi E. The Mitochondrial-Derived Peptide MOTS-c May Refine Mortality and Cardiovascular Risk Prediction in Chronic Hemodialysis Patients: A Multicenter Cohort Study. Blood purification 2024.

Neurological research · 2024 · PMID 37899006 · BioNex Evolve (PubMed-indexed)

This animal study tested MOTS-c in male mice with experimentally induced acute and chronic inflammatory pain. MOTS-c reduced pain-related behaviors and sensitivity, alongside reduced inflammation and nerve-cell activation in the spinal cord and affected paw. The researchers suggested that MOTS-c may be a potential target for inflammatory pain research.

Citation: Wang Z, Yang L, Xu L, Liao J, Lu P, Jiang J. Central and peripheral mechanism of MOTS-c attenuates pain hypersensitivity in a mice model of inflammatory pain. Neurological research 2024.

Current radiopharmaceuticals · 2024 · PMID 38314601 · BioNex Evolve (PubMed-indexed)

This observational human study measured MOTS-c and humanin in people with lung or breast cancer before, during, and after radiotherapy. Lung cancer patients had higher MOTS-c levels, which rose further with radiotherapy; breast cancer patients had lower humanin levels. Radiotherapy changed MOTS-c levels in lung cancer patients but not breast cancer patients.

Citation: Kavak AG, Karslioglu I, Saracaloglu A, Demiryürek S, Demiryürek AT. Impact of Radiation Therapy on Serum Humanin and MOTS-c Levels in Patients with Lung or Breast Cancer. Current radiopharmaceuticals 2024.

Diabetes research and clinical practice · 2024 · PMID 38636847 · BioNex Evolve (PubMed-indexed)

This animal study examined how interval exercise intensity affected naturally occurring MOTS-c and metabolic markers in male diabetic sand rats. Exercise increased MOTS-c and proteins involved in energy regulation. The moderate-intensity diabetic group showed higher levels of several metabolic proteins and reduced insulin resistance.

Citation: Parseh S, Shakerian S, Reza Tabandeh M, Habibi A. An 8-Week study on the effects of high and Moderate-Intensity interval exercises on mitochondrial MOTS-C changes and their relation to metabolic markers in male diabetic sand rats. Diabetes research and clinical practice 2024.

Theranostics · 2024 · PMID 38389837 · BioNex Evolve (PubMed-indexed)

This animal and laboratory study examined injury to the heart's small blood vessels in mice and cells exposed to a bacterial toxin. Blocking the enzyme DNA-PKcs reduced injury, while blocking MOTS-c removed that protection. Adding MOTS-c improved the protective barrier formed by blood-vessel lining cells.

Citation: Zou R, Shi W, Chang X, Zhang M, Tan S, Li R, Zhou H, Li Y, Wang G, Lv W, Fan X. The DNA-dependent protein kinase catalytic subunit exacerbates endotoxemia-induced myocardial microvascular injury by disrupting the MOTS-c/JNK pathway and inducing profilin-mediated lamellipodia degradation. Theranostics 2024.

Frontiers in Endocrinology · 2023 · PMID 36761202 · BioNex Evolve (PubMed-indexed)

This review examines how MOTS-c, a peptide made by mitochondria, affects cellular stress responses and metabolism; the abstract does not specify the species underlying the findings. It reports improved glucose metabolism in skeletal muscle and declining levels with age. The authors state that no effective method for clinical use has been developed.

Citation: Zheng Y, Wei Z, Wang T. MOTS-c: A promising mitochondrial-derived peptide for therapeutic exploitation.. Frontiers in Endocrinology 2023.

Metabolites · 2023 · PMID 36677050 · BioNex Evolve (PubMed-indexed)

This review summarized genes and cellular pathways linked to MOTS-c in metabolic disorders; the abstract does not specify the study populations. It describes potential effects on insulin resistance, obesity, muscle function, and other processes, mainly through a cellular energy-sensing pathway called AICAR–AMPK. Diagnostic and treatment applications are presented as future possibilities.

Citation: Gao Y, Wei X, Wei P, Lu H, Zhong L, Tan J, Liu H, Liu Z. MOTS-c Functionally Prevents Metabolic Disorders.. Metabolites 2023.

Scientific reports · 2023 · PMID 37957221 · BioNex Evolve (PubMed-indexed)

This animal study examined MOTS-c, alone or with aerobic exercise, in rats with type 2 diabetes. MOTS-c reduced heart-cell structural damage and improved heart function, sugar and fat metabolism, and antioxidant defenses. Combining MOTS-c with exercise produced greater improvements in some oxidative-damage and energy-signaling markers than either intervention alone.

Citation: Tang M, Su Q, Duan Y, Fu Y, Liang M, Pan Y, Yuan J, Wang M, Pang X, Ma J, Laher I, Li S. The role of MOTS-c-mediated antioxidant defense in aerobic exercise alleviating diabetic myocardial injury. Scientific reports 2023.

Frontiers in physiology · 2023 · PMID 37200834 · BioNex Evolve (PubMed-indexed)

This review examines MOTS-c research involving bone-forming and bone-resorbing cells. It reports that MOTS-c promotes bone-forming cell growth, development, and mineral deposition while inhibiting the production of bone-resorbing cells. Exercise increases MOTS-c expression, but how this influences bone regulation remains unclear.

Citation: Yi X, Hu G, Yang Y, Li J, Jin J, Chang B. Role of MOTS-c in the regulation of bone metabolism. Frontiers in physiology 2023.

Biologia futura · 2023 · PMID 37067760 · BioNex Evolve (PubMed-indexed)

This animal study examined thyroid hormones and energy-related proteins after MOTS-c was delivered directly into the brain in male rats. MOTS-c increased food consumption without changing body weight, lowered blood TSH, T3, and T4 levels, and increased the energy-related proteins UCP1 and UCP3 in tissues outside the brain.

Citation: Bahar MR, Tekin S, Beytur A, Onalan EE, Ozyalin F, Colak C, Sandal S. Effects of intracerebroventricular MOTS-c infusion on thyroid hormones and uncoupling proteins. Biologia futura 2023.

Molecular neurobiology · 2023 · PMID 37380822 · BioNex Evolve (PubMed-indexed)

This animal and lab study tested MOTS-c in rats and cultured PC12 cells exposed to rotenone, a chemical that damages dopamine-producing neurons. MOTS-c pretreatment protected against mitochondrial dysfunction and oxidative stress and reduced losses of nerve-related proteins in rats. The findings suggested that MOTS-c could directly interact with Nrf2 to activate antioxidant defenses.

Citation: Xiao J, Zhang Q, Shan Y, Ye F, Zhang X, Cheng J, Wang X, Zhao Y, Dan G, Chen M, Sai Y. The Mitochondrial-Derived Peptide (MOTS-c) Interacted with Nrf2 to Defend the Antioxidant System to Protect Dopaminergic Neurons Against Rotenone Exposure. Molecular neurobiology 2023.

Mitochondrion · 2023 · PMID 37307934 · BioNex Evolve (PubMed-indexed)

This literature review explored whether MOTS-c could have a role in pulmonary fibrosis, a disease involving lung scarring; the abstract does not specify the populations or experimental models reviewed. It describes promising effects on metabolism, cellular function, and inflammation, but presents MOTS-c as a potential research target rather than an established treatment for lung fibrosis.

Citation: Zhang Z, Chen D, Du K, Huang Y, Li X, Li Q, Lv X. MOTS-c: A potential anti-pulmonary fibrosis factor derived by mitochondria. Mitochondrion 2023.

Diabetes & metabolism journal · 2023 · PMID 36824008 · PubMed

This review examines MOTS-c research in type 1 and type 2 diabetes; the abstract does not specify the study populations or experimental models reviewed. It describes mitochondrial peptides as associated with regulation of cell metabolism and insulin action, and suggests that understanding MOTS-c may inform future therapies.

Citation: Kong BS, Lee C, Cho YM. Mitochondrial-Encoded Peptide MOTS-c, Diabetes, and Aging-Related Diseases.. Diabetes & metabolism journal 2023.

Journal of translational medicine · 2023 · PMID 36670507 · PubMed

This review examines MOTS-c in stress responses, metabolism, and aging; the abstract does not specify the populations or experimental models reviewed. It describes MOTS-c moving into the cell nucleus during stress or exercise and regulating stress-adaptation genes. The authors highlight its potential role in maintaining energy balance and supporting healthy aging.

Citation: Wan W, Zhang L, Lin Y, Rao X, Wang X, Hua F, Ying J. Mitochondria-derived peptide MOTS-c: effects and mechanisms related to stress, metabolism and aging.. Journal of translational medicine 2023.

Life sciences · 2023 · PMID 36584915 · PubMed

This animal study examined how MOTS-c and aerobic exercise affect heart structure, function, and signaling in rats. Both increased heart weight and thickened heart muscle fibers, while enhancing measures of cardiac function. The findings suggest similar effects through activation of the NRG1-ErbB4-C/EBPβ signaling pathway.

Citation: Yuan J, Xu B, Ma J, Pang X, Fu Y, Liang M, Wang M, Pan Y, Duan Y, Tang M, Zhu B, Laher I et al.. MOTS-c and aerobic exercise induce cardiac physiological adaptation via NRG1/ErbB4/CEBPβ modification in rats.. Life sciences 2023.

Pharmacological Research · 2022 · PMID 34798268 · BioNex Evolve (PubMed-indexed)

This animal and lab study examined MOTS-c in mice with experimentally induced gestational diabetes and in cell experiments. In mice, MOTS-c reduced high blood sugar, improved insulin sensitivity and glucose tolerance, and reduced offspring birth weight and deaths caused by gestational diabetes. Lab experiments also found increased glucose uptake and protection of insulin-producing cells from chemical injury.

Citation: Yin Y, Pan Y, He J, Zhong H, Wu Y, Ji C. The mitochondrial-derived peptide MOTS-c relieves hyperglycemia and insulin resistance in gestational diabetes mellitus.. Pharmacological Research 2022.

Peptides · 2022 · PMID 35842023 · BioNex Evolve (PubMed-indexed)

This laboratory study tested MOTS-c in human and mouse muscle precursor cells. MOTS-c increased formation of immature muscle fibers and blocked IL-6-induced STAT3 activity, while a modified version of the peptide did not. The findings suggest that a specific region of MOTS-c helps promote muscle cell development through STAT3 signaling.

Citation: García-Benlloch S, Revert-Ros F, Blesa JR, Alis R. MOTS-c promotes muscle differentiation in vitro.. Peptides 2022.

International journal of molecular sciences · 2022 · PMID 36233287 · PubMed

This review examines MOTS-c in aging and age-related disorders, without specifying the populations or experimental models behind the reported benefits. It reports that MOTS-c levels decline with age and that the peptide regulates genes during metabolic stress. The authors describe beneficial effects in age-related diseases and potential to reverse some aging-related changes.

Citation: Mohtashami Z, Singh MK, Salimiaghdam N, Ozgul M, Kenney MC. MOTS-c, the Most Recent Mitochondrial Derived Peptide in Human Aging and Age-Related Diseases.. International journal of molecular sciences 2022.

Frontiers in endocrinology · 2022 · PMID 35370955 · PubMed

This animal study compared MOTS-c and aerobic exercise in rats with experimentally induced type 2 diabetes. Both reduced abnormalities in heart structure and function. The findings suggest that MOTS-c activates the NRG1-ErbB4 signaling pathway and mimics exercise-related heart protection in this model.

Citation: Li S, Wang M, Ma J, Pang X, Yuan J, Pan Y, Fu Y, Laher I. MOTS-c and Exercise Restore Cardiac Function by Activating of NRG1-ErbB Signaling in Diabetic Rats.. Frontiers in endocrinology 2022.

Aging · 2022 · PMID 36490309 · PubMed

This randomized human study measured blood MOTS-c in patients with HER2-positive breast cancer receiving chemotherapy and trastuzumab, with or without metformin. Neither regimen significantly changed circulating MOTS-c. Changes also did not differ significantly according to whether patients achieved a complete pathological response, regardless of metformin use.

Citation: Cuyàs E, Verdura S, Martin-Castillo B, Menendez JA. Circulating levels of MOTS-c in patients with breast cancer treated with metformin.. Aging 2022.

Biochimica et biophysica acta. General subjects · 2021 · PMID 34520826 · PubMed

This review covers human and mouse research on exercise and mitochondrial peptides, including MOTS-c. Brief high-intensity exercise can increase humanin and MOTS-c in human muscle and blood, but evidence for lasting changes with training is conflicting. In animal studies, MOTS-c improved exercise performance and produced some exercise-like metabolic changes in mice.

Citation: Woodhead JST, Merry TL. Mitochondrial-derived peptides and exercise.. Biochimica et biophysica acta. General subjects 2021.

American journal of physiology. Endocrinology and metabolism · 2020 · PMID 32776825 · PubMed

This review examines mitochondrial peptides, including MOTS-c, in human research and animal studies in rodents. Obesity, diabetes, and aging were associated with lower circulating peptide levels, while human muscle responses varied by context. Peptide treatment enhanced insulin sensitivity and protected against age-related metabolic disorders in rodents, but whether these effects can become therapies remains undetermined.

Citation: Merry TL, Chan A, Woodhead JST, Reynolds JC, Kumagai H, Kim SJ, Lee C. Mitochondrial-derived peptides in energy metabolism.. American journal of physiology. Endocrinology and metabolism 2020.

BioEssays : news and reviews in molecular, cellular and developmental biology · 2019 · PMID 31378979 · PubMed

This review discusses laboratory findings about how MOTS-c helps mitochondria communicate with the cell nucleus. It describes MOTS-c moving into the nucleus during metabolic stress and directly regulating gene activity to support cellular balance. The authors propose that mitochondrial and nuclear genomes coordinate these adaptive responses.

Citation: Benayoun BA, Lee C. MOTS-c: A Mitochondrial-Encoded Regulator of the Nucleus.. BioEssays : news and reviews in molecular, cellular and developmental biology 2019.

Cell metabolism · 2018 · PMID 29983246 · BioNex Evolve (PubMed-indexed)

This laboratory study examined how MOTS-c, a peptide made from mitochondrial genetic instructions, affects gene activity in cells under metabolic stress. MOTS-c moved into the cell nucleus and regulated genes, including those involved in antioxidant responses, through a process dependent on the energy-sensing enzyme AMPK.

Citation: Kim KH, Son JM, Benayoun BA, Lee C. The Mitochondrial-Encoded Peptide MOTS-c Translocates to the Nucleus to Regulate Nuclear Gene Expression in Response to Metabolic Stress.. Cell metabolism 2018.

Rejuvenation research · 2018 · PMID 30058454 · PubMed

This review discusses mitochondrial peptides in lab studies of cells and animal studies in mice. Despite reported cell-protective and metabolic benefits, a recent cell study found that humanin and MOTS-c increased the secretion of immune-signaling substances by senescent cells, which have stopped dividing. The authors suggest that cell protection may permit increased inflammatory signaling.

Citation: Mendelsohn AR, Larrick JW. Mitochondrial-Derived Peptides Exacerbate Senescence.. Rejuvenation research 2018.

ClinicalTrials.gov · 2017 · NCT03878706 · ClinicalTrials.gov

This human observational study will compare blood vessel and heart function across diabetes medication groups in people with type 2 diabetes and high cardiovascular risk or heart failure with preserved pumping function. The study is recruiting, and no results are reported.

Population / model

Diabetes Mellitus, Type 2

Citation: University of Athens. The Effect of GLP-1 Agonist, SGLT2 Inhibitor and Their Combination on Endothelial Function, Arterial Stiffness and Left Ventricular Deformation in Patients With Type 2 Diabetes With High Cardiovascular Risk. ClinicalTrials.gov 2017.

ClinicalTrials.gov · 2016 · NCT06133946 · ClinicalTrials.gov

This human observational study follows newborn genetic and hearing screening in Nantong, China, with ongoing follow-up of children with hearing loss. The record lists the study as active but not recruiting, and the abstract reports no results.

Population / model

Hearing Loss

Citation: Affiliated Hospital of Nantong University. Cohort of Universal Newborn Deafness-gene Screening in Nantong City, China. ClinicalTrials.gov 2016.

Free radical biology & medicine · 2016 · PMID 27216708 · PubMed

This review discusses MOTS-c and its role in muscle and fat metabolism at the cellular and whole-body levels; the abstract does not specify the species studied. It reports that MOTS-c targets skeletal muscle and enhances glucose metabolism, with potential implications for obesity, diabetes, exercise, and longevity.

Citation: Lee C, Kim KH, Cohen P. MOTS-c: A novel mitochondrial-derived peptide regulating muscle and fat metabolism.. Free radical biology & medicine 2016.

Cell Metabolism · 2015 · editorial

This animal study examined the mitochondrial-derived peptide MOTS-c in relation to metabolic balance, obesity, and insulin resistance. The abstract was not available, so results are not summarized.

Population / model

Mice and cell cultures

Limitations

Mouse data; no human efficacy trials.

Citation: Lee C, et al.. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metabolism 2015.

ClinicalTrials.gov · 2014 · NCT04027712 · ClinicalTrials.gov

This planned observational human study examines whether MOTS-c and beta-amyloid levels are associated with platelet activity despite clopidogrel use and cardiovascular death in people with coronary artery disease and type 2 diabetes. Its status is unknown, and the abstract provides no results establishing these associations.

Population / model

Diabetes; Clopidogrel Resistance; Amyloid; Insulin Resistance

Citation: University of Athens. High On-treatment Platelet Reactivity, Increased B-amyloid and Downregulation of MOTS-c Predict Mortality in Patients With Coronary Artery Disease and Type 2 Diabetes Mellitus: a 2-year Follow up Study. ClinicalTrials.gov 2014.

Journal of minimally invasive gynecology · 2026 · PMID 40543759 · PubMed

This systematic review and meta-analysis examined treatments for women with sexual desire, arousal, or orgasm difficulties without sexual pain conditions. Bremelanotide improved overall sexual function, desire, and arousal, and reduced distress. Mindfulness-based cognitive behavioral therapy improved desire, arousal, and orgasm, while flibanserin improved desire; both also reduced distress.

Citation: Toledo RG, Winkelman WD, Reyes-Gonzalez D, Bergeron S, Fladger A, Hacker MR, Anand M. Female Sexual Desire, Arousal, and Orgasmic Dysfunctions: A Systematic Review and Meta-Analysis of Treatment Options.. Journal of minimally invasive gynecology 2026.

Neuropharmacology · 2025 · PMID 39793696 · BioNex Evolve (PubMed-indexed)

This animal study examined bremelanotide’s effects on brain receptor gene activity and sexual reward in female Syrian hamsters. Bremelanotide did not change melanocortin receptor gene activity in the dopamine reward system or enhance the rewarding effects of sexual interactions in the behavioral test.

Citation: Borland JM, Kohut-Jackson AL, Peyla AC, Hall MA, Mermelstein PG, Meisel RL. Female Syrian hamster analyses of bremelanotide, a US FDA approved drug for the treatment of female hypoactive sexual desire disorder. Neuropharmacology 2025.

ClinicalTrials.gov · 2025 · NCT06867835 · ClinicalTrials.gov

This completed, open-label human trial investigated whether bremelanotide passes into breast milk in healthy, premenopausal lactating women and how its concentration changes over time. The abstract reports no results.

Population / model

Lactating Mother

Citation: Cosette Pharmaceuticals, Inc.. A Phase 4, Open-Label Study of a Single Dose of Vyleesi® (Bremelanotide Injection) in Healthy, Premenopausal Lactating Female Subjects to Measure the Concentration of Bremelanotide in Breast Milk. ClinicalTrials.gov 2025.

Clinical obstetrics and gynecology · 2025 · PMID 39846877 · PubMed

This review evaluated medications for sexual dysfunction in women, focusing on low sexual desire and including bremelanotide, flibanserin, and investigational therapies. It discusses study outcomes, safety, and clinical management, but the abstract does not report specific efficacy or safety findings.

Citation: How A, Jowdy C, Novatcheva E, Clayton AH. Novel Pharmacologic Treatments of Female Sexual Dysfunction.. Clinical obstetrics and gynecology 2025.

Diseases (Basel, Switzerland) · 2025 · PMID 41002740 · PubMed

This review examined melanocortin receptor gene variations, immune-cell functions, and links to human diseases rather than reporting a new clinical trial. It described associations between receptor gene changes and several diseases, alongside evidence that these receptors help regulate inflammation. Drugs targeting these receptors were discussed as having potential uses in inflammatory diseases.

Citation: Bardhan M, Anand A, Javed A, Chilo MA, Khan N, Garg T, Surana A, Huang H, Samim MM, Suresh V, Khare A, Menon B et al.. Polymorphism of Melanocortin Receptor Genes-Association with Inflammatory Traits and Diseases.. Diseases (Basel, Switzerland) 2025.

Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2025 · PMID 40518469 · PubMed

This review compared sexual-health guidelines for female cancer survivors. The guidelines agreed on several aspects of care but differed on others, and evidence for medicines addressing low sexual desire, including bremelanotide, was limited. The authors identified a need for more research on drug treatments and types of counselling.

Citation: Bhinder JK, Kennedy SKF, Faouk Al Aadah C, Al-Khaifi M. 2024 SOGC, 2024 NCCN, 2022 ESO-ESMO, and 2018 ASCO: a comparison of female cancer survivorship guidelines for the management of sexual health concerns.. Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer 2025.

The Annals of pharmacotherapy · 2025 · PMID 38767282 · PubMed

This review examined medicines for distressing low sexual desire in premenopausal women, focusing on flibanserin and bremelanotide. It highlighted limited efficacy, potential side effects, and concerns about transparency in reporting. The authors concluded that further research using suitable measures of clinical benefit is needed before widespread adoption.

Citation: Barakeh D, Mdaihly H, Karaoui LR. Pharmacotherapy of Hypoactive Sexual Desire Disorder in Premenopausal Women.. The Annals of pharmacotherapy 2025.

Expert review of clinical pharmacology · 2025 · PMID 41088800 · PubMed

This review examined medicines for hot flashes and reduced sexual desire in breast cancer patients receiving endocrine therapy. It discussed newer agents, including flibanserin and bremelanotide, but noted that their clinical trials excluded breast cancer patients. Evidence specific to this population was still awaited from ongoing research.

Citation: Fuhrman J, Yun J, Indorf A. Practical considerations and emerging approaches for the management of vasomotor and sexual symptoms in breast cancer patients on endocrine therapies.. Expert review of clinical pharmacology 2025.

Journal of sex research · 2024 · PMID 36809187 · BioNex Evolve (PubMed-indexed)

This review examined how benefits were measured in bremelanotide trials involving women with hypoactive sexual desire disorder. Previously unpublished outcomes showed effects ranging from none to small. Overall benefits were statistically modest and limited to measures with little evidence that they validly assess outcomes in these women.

Citation: Spielmans GI, Ellefson EM. Small Effects, Questionable Outcomes: Bremelanotide for Hypoactive Sexual Desire Disorder. Journal of sex research 2024.

ClinicalTrials.gov · 2024 · NCT06565611 · ClinicalTrials.gov

This human trial is assessing the safety, tolerability, and effectiveness of bremelanotide combined with tirzepatide in people with obesity, using a randomized, placebo-controlled design. It is active but not recruiting, and no results are reported.

Population / model

Obesity

Citation: Palatin Technologies, Inc. A Phase II, Randomized, Double-Blind, Placebo-Controlled, Clinical Study Investigating the Safety, Tolerability, and Effectiveness of the Co-Administration of Bremelanotide With Tirzepatide (GLP-1/GIP) for the Treatment of Obesity. ClinicalTrials.gov 2024.

Cureus · 2024 · PMID 39036127 · PubMed

This review examined sexual function in women with premenstrual dysphoric disorder or premenstrual syndrome. Studies reported frequent, debilitating sexual distress before menstruation, but the evidence was understudied and had methodological limitations. Although flibanserin and bremelanotide were described as effective for female sexual dysfunction, their effects when both conditions occur together remained inconclusive.

Citation: Gollapudi M, Thomas A, Yogarajah A, Ospina D, Daher JC, Rahman A, Santistevan L, Patel RV, Abraham J, Oommen SG, Siddiqui HF. Understanding the Interplay Between Premenstrual Dysphoric Disorder (PMDD) and Female Sexual Dysfunction (FSD).. Cureus 2024.

Expert opinion on pharmacotherapy · 2023 · PMID 36242769 · BioNex Evolve (PubMed-indexed)

This review evaluated bremelanotide’s proposed mechanism and clinical trial evidence in premenopausal women with low sexual desire causing distress. Questionnaire scores improved significantly, but the overall clinical benefit appeared modest; bremelanotide appeared moderately safe and well tolerated, with nausea the most common adverse reaction. The authors highlighted placebo effects and possible expectation bias as challenges in interpreting the findings.

Citation: Cipriani S, Alfaroli C, Maseroli E, Vignozzi L. An evaluation of bremelanotide injection for the treatment of hypoactive sexual desire disorder. Expert opinion on pharmacotherapy 2023.

Nature reviews. Endocrinology · 2023 · PMID 37365323 · PubMed

This review examines preclinical and human research on the brain's melanocortin signaling system as a target for metabolic disorders. It describes this system as promising for conditions including obesity and severe weight loss, while discussing drug-development challenges. Bremelanotide is mentioned as a drug targeting these receptors, not as a demonstrated treatment for metabolic disorders.

Citation: Sweeney P, Gimenez LE, Hernandez CC, Cone RD. Targeting the central melanocortin system for the treatment of metabolic disorders.. Nature reviews. Endocrinology 2023.

Neurology international · 2022 · PMID 35076581 · BioNex Evolve (PubMed-indexed)

This review examined bremelanotide for women with hypoactive sexual desire disorder, which involves low sexual desire that causes significant distress or interpersonal difficulty. The studies reviewed showed improvements in desire, arousal, and orgasm scores compared with placebo.

Citation: Edinoff AN, Sanders NM, Lewis KB, Apgar TL, Cornett EM, Kaye AM, Kaye AD. Bremelanotide for Treatment of Female Hypoactive Sexual Desire.. Neurology international 2022.

Journal of women's health (2002) · 2022 · PMID 35147466 · BioNex Evolve (PubMed-indexed)

This review assessed bremelanotide’s safety across human clinical studies, including studies in premenopausal women with low sexual desire. Side effects were mostly mild to moderate, most commonly nausea, flushing, headache, and injection-site reactions; nausea was the main reason for stopping treatment. Small, temporary blood pressure increases were also observed.

Citation: Clayton AH, Kingsberg SA, Portman D, Sadiq A, Krop J, Jordan R, Lucas J, Simon JA. Safety Profile of Bremelanotide Across the Clinical Development Program.. Journal of women's health (2002) 2022.

Journal of women's health (2002) · 2022 · PMID 35230162 · BioNex Evolve (PubMed-indexed)

This analysis examined bremelanotide versus placebo across subgroups of premenopausal women with distressing low sexual desire in the RECONNECT trials. Bremelanotide was associated with statistically significant improvements in desire and reduced distress across age, weight, body mass index, and testosterone subgroups, with few exceptions.

Citation: Simon JA, Kingsberg SA, Portman D, Jordan R, Lucas J, Sadiq A, Krop J, Clayton AH. Prespecified and Integrated Subgroup Analyses from the RECONNECT Phase 3 Studies of Bremelanotide. Journal of women's health (2002) 2022.

CNS spectrums · 2022 · PMID 33455598 · BioNex Evolve (PubMed-indexed)

This review examined how bremelanotide may affect brain signaling relevant to low sexual desire causing distress in premenopausal women. Animal studies suggest it may activate melanocortin receptors in a brain region involved in sexual function, increasing release of dopamine, a chemical messenger linked to sexual desire.

Citation: Pfaus JG, Sadiq A, Spana C, Clayton AH. The neurobiology of bremelanotide for the treatment of hypoactive sexual desire disorder in premenopausal women. CNS spectrums 2022.

ClinicalTrials.gov · 2022 · NCT05709444 · ClinicalTrials.gov

This completed, open-label human trial studied bremelanotide alongside therapy targeting the renin-angiotensin-aldosterone system in people with type 2 diabetic kidney disease. It aimed to assess urinary protein, kidney filtering-cell function, and kidney tissue changes, but the abstract reports no results.

Population / model

Kidney Disease

Citation: Palatin Technologies, Inc. A Phase IIb, Multicenter, Open-Label, Prospective Study of Bremelanotide in Diabetic Kidney Disease to Assess the Efficacy in Reducing Urinary Protein and Maintaining Podocyte Density and Function. ClinicalTrials.gov 2022.

Current psychiatry reports · 2022 · PMID 35102537 · PubMed

This review discussed diagnosis and drug treatments for sexual dysfunction in women, including bremelanotide for low sexual desire. The authors argued that combining desire and arousal disorders into one diagnostic category is less accurate and may hinder access to effective treatments. The abstract mentions updated bremelanotide safety and efficacy evidence but gives no specific findings for it.

Citation: Lee JH, Lee JE, Harsh V, Clayton AH. Pharmacotherapy for Sexual Dysfunction in Women.. Current psychiatry reports 2022.

Current opinion in obstetrics & gynecology · 2022 · PMID 36036468 · PubMed

This review examined drug treatments for sexual dysfunction in people assigned female at birth, particularly problems related to menopause and low sexual desire. It concluded that the reviewed hormone treatments and brain-acting therapies, including bremelanotide, are safe and can improve sexual desire and satisfaction in the populations discussed. The abstract provides no separate results for bremelanotide.

Citation: Burton CS, Mishra K. Pharmacologic therapeutic options for sexual dysfunction.. Current opinion in obstetrics & gynecology 2022.

Medicina (Kaunas, Lithuania) · 2022 · PMID 35630054 · PubMed

This review examined sexual dysfunction and the effects of blood pressure medicines in women with hypertension. Sexual dysfunction appeared more common in women with hypertension than in those with normal blood pressure. Beta-blockers had relatively strong evidence of harmful effects on female sexual function, while angiotensin receptor blockers were relatively beneficial.

Citation: Zhong Q, Anderson Y. Management of Hypertension with Female Sexual Dysfunction.. Medicina (Kaunas, Lithuania) 2022.

The Urologic clinics of North America · 2022 · PMID 35428435 · PubMed

This review examined medical and nonmedical approaches to sexual dysfunction in women before and after menopause. It described female sexual dysfunction as involving overlapping biological, psychological, and social factors. Flibanserin and bremelanotide were discussed for acquired, generalized low sexual desire causing distress before menopause, while testosterone was reported effective for this condition after menopause.

Citation: Nappi RE, Tiranini L, Martini E, Bosoni D, Righi A, Cucinella L. Medical Treatment of Female Sexual Dysfunction.. The Urologic clinics of North America 2022.

Drug and therapeutics bulletin · 2021 · PMID 34642243 · BioNex Evolve (PubMed-indexed)

This review examined human clinical trial evidence and outcome measures for bremelanotide and flibanserin in women with low sexual desire. The authors reported limited benefit from flibanserin and no increase in enjoyable sexual experiences with bremelanotide. They criticized changes in trial outcomes and called for closer scrutiny of conflicts of interest and clinically meaningful benefits.

Citation: Mintzes B, Tiefer L, Cosgrove L. Bremelanotide and flibanserin for low sexual desire in women: the fallacy of regulatory precedent. Drug and therapeutics bulletin 2021.

Journal of women's health (2002) · 2021 · PMID 33538638 · BioNex Evolve (PubMed-indexed)

This human study used exit surveys and interviews with premenopausal women who completed bremelanotide trials for distressing low sexual desire. Women receiving bremelanotide described increased desire, physical arousal, and improved quality of sexual activities with their partners. Placebo recipients reported benefits such as better partner communication, but not the physiological responses described by bremelanotide recipients.

Citation: Koochaki P, Revicki D, Wilson H, Pokrzywinski R, Jordan R, Lucas J, Williams LA, Sadiq A, Krop J. The Patient Experience of Premenopausal Women Treated with Bremelanotide for Hypoactive Sexual Desire Disorder: RECONNECT Exit Study Results. Journal of women's health (2002) 2021.

Journal of sex research · 2021 · PMID 33678061 · BioNex Evolve (PubMed-indexed)

This reanalysis examined bremelanotide trial data from women with hypoactive sexual desire disorder. The author found modest benefits on incompletely reported measures of questionable validity and substantially more withdrawals due to adverse events. Trial completion and follow-up participation suggested a preference for placebo; the author concluded that bremelanotide was generally not useful and criticized the original reporting.

Citation: Spielmans GI. Re-Analyzing Phase III Bremelanotide Trials for "Hypoactive Sexual Desire Disorder" in Women. Journal of sex research 2021.

ClinicalTrials.gov · 2021 · NCT04943068 · ClinicalTrials.gov

This completed human trial evaluated the effectiveness and safety of injected bremelanotide in premenopausal women with hypoactive sexual desire disorder, with or without decreased arousal. The abstract reports no results.

Population / model

Hypoactive Sexual Desire Disorder

Citation: Kwang Dong Pharmaceutical co., ltd.. A Phase 3, Bridging, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Trial to Evaluate the Efficacy and Safety of Subcutaneously Administered Bremelanotide in Premenopausal Women With Hypoactive Sexual Desire Disorder (With or Without Decreased Arousal). ClinicalTrials.gov 2021.

Journal of midwifery & women's health · 2021 · PMID 34510696 · PubMed

This clinical review discusses low sexual desire that causes distress in women, including its biology, assessment, diagnosis, and treatment options such as bremelanotide. It emphasizes that the underlying biology remains uncertain and that assessment should consider biological, psychological, and social factors. The abstract does not report specific bremelanotide effectiveness results.

Citation: Pettigrew JA, Novick AM. Hypoactive Sexual Desire Disorder in Women: Physiology, Assessment, Diagnosis, and Treatment.. Journal of midwifery & women's health 2021.

The Annals of pharmacotherapy · 2020 · PMID 31893927 · BioNex Evolve (PubMed-indexed)

This review examined human trials of bremelanotide for hypoactive sexual desire disorder. It found statistically significant improvements in sexual desire and reductions in distress related to low desire, although the clinical benefit may be modest. Common adverse effects included nausea, facial flushing, and headache.

Citation: Mayer D, Lynch SE. Bremelanotide: New Drug Approved for Treating Hypoactive Sexual Desire Disorder.. The Annals of pharmacotherapy 2020.

Journal of pharmaceutical and biomedical analysis · 2020 · PMID 32353679 · BioNex Evolve (PubMed-indexed)

This laboratory and animal study developed a sensitive blood test to measure bremelanotide and examined its absorption after oral administration in beagle dogs. The test was validated, and the dog experiments indicated minimal oral absorption.

Citation: Sauter M, Uhl P, Burhenne J, Haefeli WE. Ultra-sensitive quantification of the therapeutic cyclic peptide bremelanotide utilizing UHPLC-MS/MS for evaluation of its oral plasma pharmacokinetics. Journal of pharmaceutical and biomedical analysis 2020.

International journal of impotence research · 2020 · PMID 33558671 · PubMed

This review examined evidence on managing low sexual desire and its potential application to transgender women. The authors suggested that options including sex therapy and medications such as bremelanotide may help, but emphasized the lack of treatment-efficacy data in transgender women. They called for more research in this population.

Citation: Cocchetti C, Ristori J, Mazzoli F, Vignozzi L, Maggi M, Fisher AD. Management of hypoactive sexual desire disorder in transgender women: a guide for clinicians.. International journal of impotence research 2020.

Obstetrics & Gynecology · 2019 · editorial

These randomized phase 3 human trials studied bremelanotide for hypoactive sexual desire disorder, a condition involving low sexual desire. The abstract was not available, so results are not summarized.

Population / model

Premenopausal women with HSDD (RECONNECT studies)

Limitations

Modest effect sizes; nausea common.

Citation: Kingsberg SA, et al.. Bremelanotide for the treatment of hypoactive sexual desire disorder: two randomized phase 3 trials. Obstetrics & Gynecology 2019.

Drugs · 2019 · PMID 31429064 · BioNex Evolve (PubMed-indexed)

This review describes bremelanotide's development for premenopausal women with acquired, generalized low sexual desire that causes distress or interpersonal difficulty. It explains that the peptide may influence brain pathways involved in sexual response through melanocortin receptors, but the abstract provides no specific clinical trial results.

Citation: Dhillon S, Keam SJ. Bremelanotide: First Approval.. Drugs 2019.

The Medical letter on drugs and therapeutics · 2019 · PMID 31381550 · BioNex Evolve (PubMed-indexed)

This review concerns bremelanotide (Vyleesi) for hypoactive sexual desire disorder, a condition involving low sexual desire. The abstract was not available, so results are not summarized.

The journal of sexual medicine · 2019 · PMID 31277966 · BioNex Evolve (PubMed-indexed)

This analysis of a human trial evaluated clinically meaningful responses to bremelanotide in premenopausal women with low sexual desire and/or sexual arousal difficulties. The researchers identified thresholds for meaningful improvement and found significantly higher responder rates than placebo across all assessed outcomes in one treatment group. Bremelanotide was reported as safe and well tolerated in the trial.

Citation: Althof S, Derogatis LR, Greenberg S, Clayton AH, Jordan R, Lucas J, Spana C. Responder Analyses from a Phase 2b Dose-Ranging Study of Bremelanotide. The journal of sexual medicine 2019.

ClinicalTrials.gov · 2019 · NCT03973047 · ClinicalTrials.gov

This completed, randomized human trial studied how often nausea occurred in healthy premenopausal women receiving bremelanotide alone or with Zofran beforehand. The abstract reports no results.

Population / model

Nausea

Citation: AMAG Pharmaceuticals, Inc.. A Phase 1, Randomized Study to Evaluate the Rate of Nausea in Healthy Premenopausal Female Subjects Treated With a Single Dose of Bremelanotide Alone or With Zofran. ClinicalTrials.gov 2019.

ClinicalTrials.gov · 2019 · NCT04179734 · ClinicalTrials.gov

This registered, placebo-controlled human trial studied how activating the melanocortin-4 receptor affects brain activity and sexual arousal during erotic visual stimuli in premenopausal women with low sexual desire. The trial is listed as completed, but the supplied record reports no results.

Population / model

Hypoactive Sexual Desire Disorder

Citation: Imperial College Healthcare NHS Trust. Physiological Study to Determine the Role of the Melanocortin-4 Receptor in Brain Activity in Women With Hypoactive Sexual Desire Disorder. ClinicalTrials.gov 2019.

Sexual medicine · 2018 · PMID 29523488 · PubMed

This review examined diagnosis and treatment evidence for women with low sexual desire that causes distress. It emphasized that biological, psychological, social, and situational factors all contribute, and described medication options as limited. At the time of publication, bremelanotide was in late-stage clinical development.

Citation: Clayton AH, Kingsberg SA, Goldstein I. Evaluation and Management of Hypoactive Sexual Desire Disorder.. Sexual medicine 2018.

Sexual medicine reviews · 2018 · PMID 29576442 · PubMed

This review compared the size of improvements in medication and psychotherapy trials involving women with distressing low sexual desire. Medications and psychotherapies showed similarly large improvements, but placebo groups improved more than wait-list groups. The authors concluded that these different comparison groups distort estimates of relative effectiveness and do not support favoring psychotherapy over medication.

Citation: Pyke RE, Clayton AH. Effect Size in Efficacy Trials of Women With Decreased Sexual Desire.. Sexual medicine reviews 2018.

Expert opinion on emerging drugs · 2018 · PMID 30251897 · PubMed

This review examined existing and investigational medicines for sexual dysfunction in women, including bremelanotide. The authors identified inadequate diagnostic categories, a lack of established trial outcome measures, and stalled development of promising drugs as barriers to progress. They also highlighted social and cultural bias as an obstacle to developing new treatments.

Citation: Miller MK, Smith JR, Norman JJ, Clayton AH. Expert opinion on existing and developing drugs to treat female sexual dysfunction.. Expert opinion on emerging drugs 2018.

Obstetrics and gynecology · 2018 · PMID 29995725 · PubMed

This systematic review and meta-analysis examined placebo responses in randomized drug trials involving women with sexual dysfunction. Sexual function improved in both placebo and medication groups, with placebo accounting for most of the treatment effect. The authors concluded that the studied medicines were, overall, minimally superior to placebo.

Citation: Weinberger JM, Houman J, Caron AT, Patel DN, Baskin AS, Ackerman AL, Eilber KS, Anger JT. Female Sexual Dysfunction and the Placebo Effect: A Meta-analysis.. Obstetrics and gynecology 2018.

Journal of hypertension · 2017 · PMID 27977473 · BioNex Evolve (PubMed-indexed)

This randomized human trial studied bremelanotide’s effects on blood pressure and heart rate in premenopausal women with sexual dysfunction and normal or controlled high blood pressure. Portable monitoring detected small, temporary blood pressure increases accompanied by reduced heart rate. Discontinuations due to blood pressure increases were similar across treatment and placebo groups.

Citation: White WB, Myers MG, Jordan R, Lucas J. Usefulness of ambulatory blood pressure monitoring to assess the melanocortin receptor agonist bremelanotide. Journal of hypertension 2017.

Clinical therapeutics · 2017 · PMID 28189361 · BioNex Evolve (PubMed-indexed)

This randomized human trial tested the safety of intranasal bremelanotide with and without alcohol in healthy men and women. The combination was found to be safe and generally well tolerated under the study conditions, with no clinically significant interaction in how the substances were processed. No significant drug-related low blood pressure effects or serious adverse events were reported.

Citation: Clayton AH, Lucas J, DeRogatis LR, Jordan R. Phase I Randomized Placebo-controlled, Double-blind Study of the Safety and Tolerability of Bremelanotide Coadministered With Ethanol in Healthy Male and Female Participants. Clinical therapeutics 2017.

Therapeutic advances in chronic disease · 2017 · PMID 28203348 · PubMed

This review examined flibanserin and other approaches to distressing low sexual desire in women before and after menopause. Several medicines, including bremelanotide, had shown some clinical benefit, but trials had important design limitations and limited applicability to broader populations. The review also described side effects and other limitations of flibanserin.

Citation: Gelman F, Atrio J. Flibanserin for hypoactive sexual desire disorder: place in therapy.. Therapeutic advances in chronic disease 2017.

Women's health (London, England) · 2016 · PMID 27181790 · BioNex Evolve (PubMed-indexed)

This randomized, placebo-controlled human trial evaluated bremelanotide in premenopausal women with sexual dysfunction. The pooled bremelanotide groups analyzed showed greater improvements in satisfying sexual events, sexual function, and sexual distress than placebo. The authors described it as safe and well tolerated in this trial; reported adverse events included nausea, flushing, and headache.

Citation: Clayton AH, Althof SE, Kingsberg S, DeRogatis LR, Kroll R, Goldstein I, Kaminetsky J, Spana C, Lucas J, Jordan R, Portman DJ. Bremelanotide for female sexual dysfunctions in premenopausal women: a randomized, placebo-controlled dose-finding trial. Women's health (London, England) 2016.

ClinicalTrials.gov · 2015 · NCT02338960 · ClinicalTrials.gov

This completed human trial compared bremelanotide with placebo in premenopausal women with hypoactive sexual desire disorder, with or without decreased arousal. It was designed to evaluate effectiveness and safety, but the abstract reports no results.

Population / model

Hypoactive Sexual Desire Disorder

Citation: Palatin Technologies, Inc. Phase 3, Randomized, Double-blind, Placebo-controlled, Trial With an Open-label Extension Phase to Evaluate the Efficacy and Safety of Subcutaneously Bremelanotide in Premenopausal Women With Hypoactive Sexual Desire Disorder (HSDD). ClinicalTrials.gov 2015.

ClinicalTrials.gov · 2011 · NCT01382719 · ClinicalTrials.gov

This completed human trial was designed to compare bremelanotide with placebo for safety and effectiveness in premenopausal women with sexual arousal difficulties, low sexual desire, or both. The abstract describes the study design but reports no results.

Population / model

Female Sexual Arousal Disorder; Hypoactive Sexual Desire Disorder

Citation: Palatin Technologies, Inc. A Placebo-controlled, Randomized, Parallel Group, Dose-finding Trial to Evaluate the Efficacy and Safety of Subcutaneously Administered Bremelanotide in Premenopausal Women With FSAD (Female Sexual Arousal Disorder) and/or HSDD (Hypoactive Sexual Desire Disorder). ClinicalTrials.gov 2011.

The Urologic clinics of North America · 2011 · PMID 21621083 · PubMed

This review examined medicines acting on the brain and spinal cord for erectile dysfunction in men, including nasal bremelanotide and apomorphine. Several agents showed potential to improve erectile function, but evidence on effectiveness and tolerability remained inadequate.

Citation: Kumar R, Nehra A. Central nervous system agents and erectile dysfunction.. The Urologic clinics of North America 2011.

The Journal of urology · 2008 · PMID 18206919 · BioNex Evolve (PubMed-indexed)

This randomized human trial compared nasal bremelanotide with placebo in men whose erectile dysfunction had not responded to sildenafil. Bremelanotide produced more positive clinical results and greater intercourse satisfaction, but also more drug-related adverse effects. The authors stated that further studies were needed before drawing final conclusions about efficacy.

Citation: Safarinejad MR, Hosseini SY. Salvage of sildenafil failures with bremelanotide: a randomized, double-blind, placebo controlled study. The Journal of urology 2008.

The journal of sexual medicine · 2008 · PMID 18179455 · BioNex Evolve (PubMed-indexed)

This retracted article described a randomized, placebo-controlled trial of bremelanotide in women with arousal disorder. The journal withdrew it after reviewers raised concerns about the methods, results, and statistical interpretation, and the author did not respond to requests for original data and explanations. The journal stated that it could no longer verify the results or methods.

Citation: Safarinejad MR. RETRACTED: Evaluation of the safety and efficacy of bremelanotide, a melanocortin receptor agonist, in female subjects with arousal disorder: a double-blind placebo-controlled, fixed dose, randomized study. The journal of sexual medicine 2008.

The journal of sexual medicine · 2007 · PMID 17958619 · BioNex Evolve (PubMed-indexed)

This animal research review examined bremelanotide’s effects on sexual behavior and brain activity in female rats. Bremelanotide selectively increased behaviors that invite sexual activity, without changing how rats paced encounters or their mating posture. The findings suggest it may act by activating dopamine signaling in a brain region involved in sexual behavior.

Citation: Pfaus J, Giuliano F, Gelez H. Bremelanotide: an overview of preclinical CNS effects on female sexual function. The journal of sexual medicine 2007.

The journal of sexual medicine · 2006 · PMID 16839319 · BioNex Evolve (PubMed-indexed)

This preliminary randomized human trial compared intranasal bremelanotide with placebo in premenopausal women with sexual arousal disorder. More women reported moderate or high desire, and those attempting intercourse more often reported satisfaction with their arousal after bremelanotide. Measured genital blood-flow responses to erotic videos did not differ significantly.

Citation: Diamond LE, Earle DC, Heiman JR, Rosen RC, Perelman MA, Harning R. An effect on the subjective sexual response in premenopausal women with sexual arousal disorder by bremelanotide (PT-141), a melanocortin receptor agonist.. The journal of sexual medicine 2006.

2006 · PMID 31369224 · BioNex Evolve (PubMed-indexed)

This record concerns bremelanotide. The abstract was not available, so results are not summarized.

ClinicalTrials.gov · 2006 · NCT00425256 · ClinicalTrials.gov

This registered human trial was designed to compare intranasal bremelanotide with placebo for safety and effectiveness in women with female sexual arousal disorder during at-home use. The trial is listed as completed, but the supplied record reports no results.

Population / model

Sexual Arousal Disorder

Citation: Palatin Technologies, Inc. Evaluate the Safety and Efficacy of Bremelanotide in Women With Female Sexual Arousal Disorder (FSAD). ClinicalTrials.gov 2006.

Urology · 2005 · PMID 15833522 · BioNex Evolve (PubMed-indexed)

This randomized human trial studied nasal PT-141 combined with sildenafil in men with erectile dysfunction who reported responding to sildenafil or vardenafil. The combination produced a significantly greater erectile response to visual sexual stimulation than sildenafil alone. It was reported as safe and well tolerated in this trial, with no new or more frequent or severe adverse events.

Citation: Diamond LE, Earle DC, Garcia WD, Spana C. Co-administration of low doses of intranasal PT-141, a melanocortin receptor agonist, and sildenafil to men with erectile dysfunction results in an enhanced erectile response. Urology 2005.

Current opinion in investigational drugs (London, England : 2000) · 2004 · PMID 15134289 · BioNex Evolve (PubMed-indexed)

This historical review describes PT-141 nasal spray development for erectile dysfunction and female sexual dysfunction. It reports that a phase IIb human trial in patients with erectile dysfunction had been completed and phase III trials were planned at the time. The abstract provides no trial results.

Citation: Hedlund P. PT-141 Palatin.. Current opinion in investigational drugs (London, England : 2000) 2004.

International journal of impotence research · 2004 · PMID 14999221 · BioNex Evolve (PubMed-indexed)

These human studies evaluated injected PT-141 in healthy men and men with erectile dysfunction who reported an inadequate response to Viagra. PT-141 produced statistically significant erectile responses in both groups under the tested conditions. The researchers reported that it was safe and well tolerated in these studies.

Citation: Rosen RC, Diamond LE, Earle DC, Shadiack AM, Molinoff PB. Evaluation of the safety, pharmacokinetics and pharmacodynamic effects of subcutaneously administered PT-141, a melanocortin receptor agonist, in healthy male subjects and in patients with an inadequate response to Viagra. International journal of impotence research 2004.

International journal of impotence research · 2004 · PMID 14963471 · BioNex Evolve (PubMed-indexed)

These placebo-controlled human studies evaluated nasal PT-141 in healthy men and men with mild-to-moderate erectile dysfunction who responded to sildenafil. PT-141 produced statistically significant erectile responses compared with placebo under the tested conditions and was reported as well tolerated. Flushing and nausea were the most common adverse events.

Citation: Diamond LE, Earle DC, Rosen RC, Willett MS, Molinoff PB. Double-blind, placebo-controlled evaluation of the safety, pharmacokinetic properties and pharmacodynamic effects of intranasal PT-141, a melanocortin receptor agonist, in healthy males and patients with mild-to-moderate erectile dysfunction. International journal of impotence research 2004.

Annals of the New York Academy of Sciences · 2003 · PMID 12851303 · BioNex Evolve (PubMed-indexed)

This research examined PT-141 in rats, nonhuman primates, men without erectile dysfunction, and men with erectile dysfunction. PT-141 produced penile erections in animals and rapidly increased erectile activity in men; rat experiments also showed activation of neurons in a relevant brain region. The findings suggested promise for sexual dysfunction treatment, rather than establishing effectiveness.

Citation: Molinoff PB, Shadiack AM, Earle D, Diamond LE, Quon CY. PT-141: a melanocortin agonist for the treatment of sexual dysfunction. Annals of the New York Academy of Sciences 2003.

British journal of pharmacology · 2025 · PMID 40692165 · BioNex Evolve (PubMed-indexed)

This animal and lab study examined Semax in female mice with spinal cord injury and in a cell model of nerve inflammation. Semax improved functional recovery in mice and reduced oxidative stress and inflammatory cell death in the models. The findings linked these effects to opioid receptors and a pathway that removes molecular tags from proteins.

Citation: Liu R, Chen Y, Huang H, Li X, Lv J, Jiang L, Jiang H, Wu C, Chen W, Xu H, Zhu Z, Cai H. Semax peptide targets the μ opioid receptor gene Oprm1 to promote deubiquitination and functional recovery after spinal cord injury in female mice.. British journal of pharmacology 2025.

Bioinorganic chemistry and applications · 2025 · PMID 40496623 · BioNex Evolve (PubMed-indexed)

This lab study examined Semax in copper–amyloid-beta reactions and cultured SH-SY5Y cells. Semax removed copper from amyloid-beta complexes, altered their chemical cycling, and reduced production of reactive oxygen molecules. The cell findings suggest that Semax has protective properties against oxidative stress caused by copper-driven amyloid-beta oxidation.

Citation: Tomasello MF, Di Rosa MC, Naletova I, Sciacca MFM, Giuffrida A, Maccarrone G, Attanasio F. Semax, a Copper Chelator Peptide, Decreases the Cu(II)-Catalyzed ROS Production and Cytotoxicity of aβ by Metal Ion Stripping and Redox Silencing.. Bioinorganic chemistry and applications 2025.

Acta naturae · 2025 · PMID 41479572 · BioNex Evolve (PubMed-indexed)

This animal study tested Semax and a derivative in genetically modified mice used as a model of Alzheimer's disease. Both peptides improved cognitive function in behavioral tests and reduced amyloid deposits in the cortex and hippocampus.

Citation: Radchenko AI, Kuzubova EV, Apostol AA, Mitkevich VA, Andreeva LA, Limborska SA, Stepenko YV, Shmigerova VS, Solin AV, Korokin MV, Pokrovskii MV, Myasoedov NF. The Potential of the Peptide Drug Semax and Its Derivative for Correcting Pathological Impairments in the Animal Model of Alzheimer's Disease.. Acta naturae 2025.

Bulletin of experimental biology and medicine · 2025 · PMID 41171324 · BioNex Evolve (PubMed-indexed)

This lab study examined Semax’s effects on calcium signals in nerve cells within rat brain slices. Semax increased the frequency of spontaneous calcium fluctuations in hippocampal cells but did not significantly affect acid-triggered calcium increases in cerebellar cells. The findings suggest its protective mechanism is not related to reducing calcium entry through acid-sensing channels in those cerebellar cells.

Citation: Kolbaev SN, Sharonova IN, Skrebitsky VG. The Effect of Peptide Semax, an ACTH(4-10) Analogue, on Intracellular Calcium Dynamics in Rat Brain Neurons. Bulletin of experimental biology and medicine 2025.

International journal of molecular sciences · 2025 · PMID 40650034 · BioNex Evolve (PubMed-indexed)

This animal study examined how Semax and another ACTH-like peptide affected gene activity in rat brain regions after an experimentally induced stroke. Both peptides tended to normalize disrupted gene activity, but effects differed by brain region. The other peptide also worsened some gene-activity disturbances in the striatum, mainly involving inflammation.

Citation: Filippenkov IB, Shpetko YY, Ales DA, Stavchansky VV, Denisova AE, Yuzhakov VV, Fomina NK, Gubsky LV, Andreeva LA, Myasoedov NF, Limborska SA, Dergunova LV. Genes That Associated with Action of ACTH-like Peptides with Neuroprotective Potential in Rat Brain Regions with Different Degrees of Ischemic Damage. International journal of molecular sciences 2025.

Neuropeptides · 2025 · PMID 41004910 · PubMed

This review examined peptides and proteins, including Semax, in preclinical studies and early human trials of neurodegenerative diseases. It reports effects on oxidative stress, inflammation, cellular energy systems, and nerve-cell connections. The authors highlight potential protective benefits but emphasize delivery challenges and the need for further clinical validation.

Citation: Giri S, Chandra P. Modulation of neuropathological pathways by bioactive peptides and proteins/polypeptides: Targeting oxidative stress in neurodegenerative diseases.. Neuropeptides 2025.

European journal of pharmacology · 2024 · PMID 39442746 · BioNex Evolve (PubMed-indexed)

This animal study tested Semax and Melanotan II in male rats exposed to chronic unpredictable stress. Both peptides reversed or reduced loss of pleasure-seeking behavior, suppressed weight gain, adrenal enlargement, and reductions in a brain protein involved in nerve-cell support. Neither peptide changed immobility in the forced-swim test.

Citation: Inozemtseva LS, Yatsenko KA, Glazova NY, Kamensky AA, Myasoedov NF, Levitskaya NG, Grivennikov IA, Dolotov OV. Antidepressant-like and antistress effects of the ACTH(4-10) synthetic analogs Semax and Melanotan II on male rats in a model of chronic unpredictable stress. European journal of pharmacology 2024.

Biochemistry. Biokhimiia · 2024 · PMID 39418522 · PubMed

This animal study examined gene activity in the frontal brain region of rats given Semax or a related ACTH-like peptide under normal conditions. Both peptides mainly reduced activity of immune-related genes. Differences between their effects involved genes linked to nerve signaling and ion-channel regulation.

Citation: Filippenkov IB, Glazova NY, Sebentsova EA, Stavchansky VV, Andreeva LA, Myasoedov NF, Levitskaya NG, Limborska SA, Dergunova LV. Changes of Transcriptomic Activity in Rat Brain Cells under the Influence of Synthetic Adrenocorticotropic Hormone-Like Peptides.. Biochemistry. Biokhimiia 2024.

ClinicalTrials.gov · 2023 · NCT05832060 · ClinicalTrials.gov

This registered human trial was designed to compare two forms of electrical brain stimulation with sham stimulation for improving reading skills in children and adolescents with dyslexia. Its status is unknown, and the abstract presents expected benefits and safety as hypotheses rather than results.

Population / model

Developmental Dyslexia

Citation: Bambino Gesù Hospital and Research Institute. Comparing the Efficacy of tDCS and tRNS to Improve Reading Skills in Children and Adolescents With Dyslexia. ClinicalTrials.gov 2023.

ACS chemical neuroscience · 2022 · PMID 35080861 · BioNex Evolve (PubMed-indexed)

This lab study tested how Semax affected amyloid-beta clumping and copper interactions in artificial membrane models and laboratory assays, not in people. Semax prevented amyloid-beta–copper complexes from forming and showed anti-clumping and protective properties, especially when copper was present. The findings suggest that Semax inhibits amyloid fiber formation by interfering with these complexes.

Citation: Sciacca MFM, Naletova I, Giuffrida ML, Attanasio F. Semax, a Synthetic Regulatory Peptide, Affects Copper-Induced Abeta Aggregation and Amyloid Formation in Artificial Membrane Models.. ACS chemical neuroscience 2022.

Bulletin of experimental biology and medicine · 2022 · PMID 36322304 · BioNex Evolve (PubMed-indexed)

This animal study tested Selank in morphine-dependent rats whose withdrawal was triggered by naloxone. Selank reduced overall withdrawal signs, including convulsive reactions, drooping eyelids, and posture problems, and raised the threshold for responding to touch. Its effects were slightly weaker than those of diazepam.

Citation: Konstantinopolsky MA, Chernyakova IV, Kolik LG. Selank, a Peptide Analog of Tuftsin, Attenuates Aversive Signs of Morphine Withdrawal in Rats. Bulletin of experimental biology and medicine 2022.

Genes · 2022 · PMID 36553646 · PubMed

This animal study examined inflammation-related and nerve-signaling gene activity in rats after brain blood flow was blocked and restored. Unlike previously reported effects of Semax, the related peptides PGP and PGPL mostly left the measured gene activity unchanged. Some genes responded differently to these peptides than to Semax.

Citation: Stavchansky VV, Filippenkov IB, Remizova JA, Denisova AE, Mozgovoy IV, Gubsky LV, Myasoedov NF, Andreeva LA, Limborska SA, Dergunova LV. Insight into Glyproline Peptides' Activity through the Modulation of the Inflammatory and Neurosignaling Genetic Response Following Cerebral Ischemia-Reperfusion.. Genes 2022.

International Journal of Molecular Sciences · 2021 · DOI 10.3390/ijms22126179 · BioNex Evolve

This animal study examined brain protein expression and the protective effects of Semax in rats after interrupted and restored blood flow to the brain. The abstract was not available, so results are not summarized.

Neuropeptides · 2021 · PMID 33418449 · BioNex Evolve (PubMed-indexed)

This animal study examined whether Semax could reduce long-term effects of early-life exposure to the antidepressant fluvoxamine in rats. Fluvoxamine exposure disrupted anxiety-related behavior, learning, and brain chemical levels. Subsequent Semax administration reduced anxiety-like behavior, improved learning, and normalized the brain chemical levels affected by fluvoxamine.

Citation: Glazova NY, Manchenko DM, Volodina MA, Merchieva SA, Andreeva LA, Kudrin VS, Myasoedov NF, Levitskaya NG. Semax, synthetic ACTH(4-10) analogue, attenuates behavioural and neurochemical alterations following early-life fluvoxamine exposure in white rats.. Neuropeptides 2021.

Current reviews in clinical and experimental pharmacology · 2021 · PMID 32621722 · BioNex Evolve (PubMed-indexed)

This animal study examined Selank's effects on immune-signaling proteins in male rats exposed to social stress. Stress increased several of these proteins, and Selank reduced some toward control levels, which the authors interpreted as stress-protective activity. The abstract inconsistently refers to Semax in one part of its results.

Citation: Leonidovna YA, Aleksandrovna SM, Aleksandrovna TA, Aleksandrovna BO, Fedorovich MN, Aleksandrovna AL. The Influence of Selank on the Level of Cytokines Under the Conditions of "Social" Stress. Current reviews in clinical and experimental pharmacology 2021.

Bulletin of experimental biology and medicine · 2021 · PMID 33459919 · BioNex Evolve (PubMed-indexed)

This animal study examined Semax’s effects on the colon in male rats exposed to restraint stress. Semax lowered the stress hormone corticosterone, reduced stress-related tissue damage, and promoted adaptation of the intestinal wall to stress.

Citation: Svishcheva MV, Mishina YS, Medvedeva OA, Bobyntsev II, Mukhina AY, Kalutskii PV, Andreeva LA, Myasoedov NF. Morphofunctional State of the Large Intestine in Rats under Conditions of Restraint Stress and Administration of Peptide ACTH_(4-7)-PGP (Semax). Bulletin of experimental biology and medicine 2021.

Genes (Basel) · 2020 · DOI 10.3390/genes11060681 · BioNex Evolve

This animal study examined gene activity related to the protective properties of Semax in rats after interrupted and restored blood flow to the brain. The abstract was not available, so results are not summarized.

Doklady biological sciences : proceedings of the Academy of Sciences of the USSR, Biological sciences sections · 2020 · PMID 32342318 · BioNex Evolve (PubMed-indexed)

This human study used resting-state brain scans to examine Selank and Semax effects in healthy participants compared with placebo. Researchers identified shared and distinct effects on functional connectivity, meaning coordinated brain activity, between the right amygdala and the right temporal cortex.

Citation: Panikratova YR, Lebedeva IS, Sokolov OY, Rumshiskaya AD, Kupriyanov DA, Kost NV, Myasoedov NF. Functional Connectomic Approach to Studying Selank and Semax Effects.. Doklady biological sciences : proceedings of the Academy of Sciences of the USSR, Biological sciences sections 2020.

Bulletin of experimental biology and medicine · 2020 · PMID 32651826 · BioNex Evolve (PubMed-indexed)

This animal study examined Selank's effects on the colon wall in male rats exposed to repeated restraint stress. Selank reduced levels of the stress hormone corticosterone, lessened stress-related tissue damage, and accelerated adaptation to stress.

Citation: Mukhina AY, Mishina ES, Bobyntsev II, Medvedeva OA, Svishcheva MV, Kalutskii PV, Andreeva LA, Myasoedov NF. Morphological Changes in the Large Intestine of Rats Subjected to Chronic Restraint Stress and Treated with Selank. Bulletin of experimental biology and medicine 2020.

Bulletin of experimental biology and medicine · 2020 · PMID 32737723 · BioNex Evolve (PubMed-indexed)

This animal study examined Semax’s effects on colon bacteria in male rats exposed to restraint stress. Stress reduced normally resident bacteria and increased potentially harmful microorganisms; Semax prevented these changes under some tested conditions. The authors suggested that effects on the nervous system and intestinal receptors might explain the findings.

Citation: Svishcheva MV, Mukhina AY, Medvedeva OA, Shevchenko AV, Bobyntsev II, Kalutskii PV, Andreeva LA, Myasoedov NF. Composition of Colon Microbiota in Rats Treated with ACTH(4-7)-PGP Peptide (Semax) under Conditions of Restraint Stress. Bulletin of experimental biology and medicine 2020.

Bulletin of experimental biology and medicine · 2020 · PMID 32246363 · PubMed

This animal study tested deltalicin and Semax in rats with experimentally induced diabetes. Both peptides, along with the comparator sulodexide, reduced total cholesterol, triglycerides, and LDL cholesterol while increasing HDL cholesterol. Deltalicin had stronger effects than Semax and sulodexide on total cholesterol, LDL cholesterol, and an index of artery-clogging risk.

Citation: Elagina AA, Lyashev YD, Lyashev AY, Pronyaeva TV, Chahine AR. Correction of Lipid Metabolism Disorders in Diabetes Mellitus with Peptide Drugs.. Bulletin of experimental biology and medicine 2020.

Bulletin of experimental biology and medicine · 2019 · PMID 31243679 · BioNex Evolve (PubMed-indexed)

This animal study examined Selank's effects on liver tissue in male rats exposed to chronic foot-shock stress. Selank reduced the severity of stress-related degenerative changes and, under some tested conditions, restored the balance between liver-cell nucleus and cytoplasm size.

Citation: Fomenko EV, Bobyntsev II, Ivanov AV, Belykh AE, Andreeva LA, Myasoedov NF. Effect of Selank on Morphological Parameters of Rat Liver in Chronic Foot-Shock Stress.. Bulletin of experimental biology and medicine 2019.

Bulletin of experimental biology and medicine · 2019 · PMID 31236882 · BioNex Evolve (PubMed-indexed)

This animal study tested Selank’s effects on gut microbes in male rats exposed to repeated restraint stress. Stress reduced normally resident microbes and increased potentially harmful ones, while Selank restored the gut microbial community. The researchers proposed nervous-system and immune mechanisms as possible explanations.

Citation: Mukhina AY, Medvedeva OA, Svishcheva MV, Shevchenko AV, Efremova NN, Bobyntsev II, Kalutskii PV, Andreeva LA, Myasoedov NF. State of Colon Microbiota in Rats during Chronic Restraint Stress and Selank Treatment. Bulletin of experimental biology and medicine 2019.

Bulletin of experimental biology and medicine · 2019 · PMID 31625062 · BioNex Evolve (PubMed-indexed)

This animal study examined Selank’s effects on memory and the brain protein BDNF in rats exposed to long-term alcohol consumption. Selank prevented alcohol-withdrawal-related memory and attention disturbances and improved object-recognition performance in rats not exposed to alcohol. Tests of brain tissue also showed that Selank prevented alcohol-induced increases in BDNF in the hippocampus and frontal cortex.

Citation: Kolik LG, Nadorova AV, Antipova TA, Kruglov SV, Kudrin VS, Durnev AD. Selank, Peptide Analogue of Tuftsin, Protects Against Ethanol-Induced Memory Impairment by Regulating of BDNF Content in the Hippocampus and Prefrontal Cortex in Rats. Bulletin of experimental biology and medicine 2019.

Bulletin of experimental biology and medicine · 2019 · PMID 31028579 · BioNex Evolve (PubMed-indexed)

This animal study examined Semax’s effects on immune responses disrupted by experimentally induced social stress. Semax restored cell-based and antibody-related immune responses, along with the ability of neutrophils to engulf particles. The authors interpreted these findings as evidence of immune-modulating properties and called for further research.

Citation: Samotrueva MA, Yasenyavskaya AL, Murtalieva VK, Bashkina OA, Myasoedov NF, Andreeva LA, Karaulov AV. Experimental Substantiation of Application of Semax as a Modulator of Immune Reaction on the Model of "Social" Stress. Bulletin of experimental biology and medicine 2019.

Protein and peptide letters · 2018 · PMID 30255741 · BioNex Evolve (PubMed-indexed)

This animal laboratory study used brain-cell membranes to investigate how Selank might produce anti-anxiety effects. Selank enhanced GABA binding by modifying receptor activity and altered the effects of some other drugs on that binding. The findings suggest that selective modulation of GABA receptors may be one mechanism behind its anti-anxiety effects.

Citation: Vyunova TV, Andreeva L, Shevchenko K, Myasoedov N. Peptide-based Anxiolytics: The Molecular Aspects of Heptapeptide Selank Biological Activity.. Protein and peptide letters 2018.

Bulletin of experimental biology and medicine · 2018 · PMID 30225715 · BioNex Evolve (PubMed-indexed)

This human study used resting-state brain scans to compare healthy volunteers receiving Semax or placebo. The Semax group showed a greater volume of the medial frontal component of the brain's default mode network than controls. The study demonstrated the location of Semax-related effects on this brain network.

Citation: Lebedeva IS, Panikratova YR, Sokolov OY, Kupriyanov DA, Rumshiskaya AD, Kost NV, Myasoedov NF. Effects of Semax on the Default Mode Network of the Brain.. Bulletin of experimental biology and medicine 2018.

Bulletin of experimental biology and medicine · 2018 · PMID 29577196 · BioNex Evolve (PubMed-indexed)

This lab study examined Semax’s effects on electrical currents triggered by GABA and glycine in isolated rat brain neurons. Semax increased GABA-triggered currents in cerebellar cells and reduced glycine-triggered currents in hippocampal cells. These effects developed slowly and were difficult to reverse, suggesting involvement of signaling processes inside the cells.

Citation: Sharonova IN, Bukanova YV, Myasoedov NF, Skrebitskii VG. Modulation of GABA- and Glycine-Activated Ionic Currents with Semax in Isolated Cerebral Neurons. Bulletin of experimental biology and medicine 2018.

Frontiers in pharmacology · 2017 · PMID 28293190 · BioNex Evolve (PubMed-indexed)

This lab study examined how Selank, GABA, and olanzapine affected genes involved in nerve-cell signaling in IMR-32 neuroblastoma cells. Selank alone did not change the activity of the genes studied, but it nearly eliminated GABA-related changes and broadened the changes seen with olanzapine. The findings partially support the hypothesis that Selank may affect how GABA interacts with its receptors.

Citation: Filatova E, Kasian A, Kolomin T, Rybalkina E, Alieva A, Andreeva L, Limborska S, Myasoedov N, Pavlova G, Slominsky P, Shadrina M. GABA, Selank, and Olanzapine Affect the Expression of Genes Involved in GABAergic Neurotransmission in IMR-32 Cells.. Frontiers in pharmacology 2017.

Bulletin of experimental biology and medicine · 2017 · PMID 28853100 · BioNex Evolve (PubMed-indexed)

This animal study examined Selank’s effects on liver and blood markers in male rats exposed to restraint stress. Under acute stress, Selank increased overall antioxidant activity in the liver, while other effects varied across experimental conditions. Under chronic stress, it reduced liver superoxide dismutase activity, a marker of oxidative damage, and blood AST enzyme activity; other measured markers were unchanged.

Citation: Fomenko EV, Bobyntsev II, Kryukov AA, Ivanov AV, Andreeva LA, Myasoedov NF. Effect of Selank on Functional State of Rat Hepatocytes under Conditions of Restraint Stress. Bulletin of experimental biology and medicine 2017.

Bulletin of experimental biology and medicine · 2017 · PMID 28361410 · BioNex Evolve (PubMed-indexed)

This laboratory study tested Selank in slices of rat hippocampus, a brain region involved in memory. Selank increased the strength and frequency of spontaneous inhibitory signals in the studied nerve cells. In some cells, this increase was preceded by a temporary decrease.

Citation: Povarov IS, Kondratenko RV, Derevyagin VI, Myasoedov NF, Skrebitsky VG. Effect of Selank on Spontaneous Synaptic Activity of Rat Hippocampal CA1 Neurons. Bulletin of experimental biology and medicine 2017.

Doklady biological sciences : proceedings of the Academy of Sciences of the USSR, Biological sciences sections · 2017 · PMID 28702721 · BioNex Evolve (PubMed-indexed)

This animal study tested Semax and Selank in rats with chemically induced Parkinson-like damage to dopamine-producing nerve cells. Neither peptide changed movement in the maze test or passive defensive behavior. Selank reduced anxiety in the maze test.

Citation: Slominsky PA, Shadrina MI, Kolomin TA, Stavrovskaya AV, Filatova EV, Andreeva LA, Illarioshkin SN, Myasoedov NF. Peptides semax and selank affect the behavior of rats with 6-OHDA induced PD-like parkinsonism. Doklady biological sciences : proceedings of the Academy of Sciences of the USSR, Biological sciences sections 2017.

Bulletin of experimental biology and medicine · 2017 · PMID 28948544 · BioNex Evolve (PubMed-indexed)

This animal study examined Semax’s effects on changes in the heart’s sympathetic nerve supply after an experimentally induced heart attack in rats. Semax reduced nerve growth in the wall separating the heart’s ventricles, but did not change the density of beta-adrenergic receptors.

Citation: Gavrilova SA, Markov MA, Berdalin AB, Kurenkova AD, Koshelev VB. Changes in Sympathetic Innervation of the Heart in Rats with Experimental Myocardial Infarction. Effect of Semax. Bulletin of experimental biology and medicine 2017.

Journal of molecular recognition : JMR · 2017 · PMID 27921334 · PubMed

This laboratory study examined how Semax and its breakdown products bind to nerve-cell membranes. Some fragments competed for Semax binding sites, while others had their own binding characteristics. The authors propose that Semax and its fragments act together as an interacting regulatory system, rather than through Semax alone.

Citation: Vyunova TV, Andreeva LA, Shevchenko KV, Myasoedov NF. Synacton and individual activity of synthetic and natural corticotropins.. Journal of molecular recognition : JMR 2017.

Bulletin of experimental biology and medicine · 2017 · PMID 29181670 · PubMed

This animal study used a laboratory blood-clotting test to examine glyproline peptides, including Selank; the abstract does not identify the species. The tested peptides shifted clotting measurements toward reduced clot formation, with Selank showing the strongest anticoagulant effect.

Citation: Rogozinskaya EY, Lyapina MG. Anticoagulant Effects of Arginine-Containing Peptides of the Glyproline Family (His-Phe-Arg-Trp-Pro-Gly-Pro and Thr-Lys-Pro-Arg-Pro-Gly-Pro) Revealed by Thromboelastography.. Bulletin of experimental biology and medicine 2017.

Bulletin of experimental biology and medicine · 2016 · PMID 27878720 · BioNex Evolve (PubMed-indexed)

This animal study examined Selank’s effects on alcohol-induced movement and behavioral sensitization in male mice. Selank prevented alcohol-induced excessive movement and blocked the expression of an increased movement response associated with repeated alcohol exposure, without preventing that sensitization from developing. The authors suggested that Selank may influence alcohol’s motivational effects.

Citation: Kolik LG, Nadorova AV, Seredenin SB. Selank Inhibits Ethanol-Induced Hyperlocomotion and Manifestation of Behavioral Sensitization in DBA/2 Mice. Bulletin of experimental biology and medicine 2016.

Doklady biological sciences : proceedings of the Academy of Sciences of the USSR, Biological sciences sections · 2016 · PMID 27411820 · BioNex Evolve (PubMed-indexed)

This animal study examined Semax, vitamin C, and heavy-metal salts in a learned avoidance task in rats. The metal salts impaired the avoidance response, while Semax counteracted this impairment to a degree comparable to vitamin C. The authors interpreted the findings as confirming Semax’s antioxidant properties.

Citation: Inozemtsev AN, Bokieva SB, Karpukhina OV, Gumargalieva KZ, Kamensky AA, Myasoedov NF. Semax prevents learning and memory inhibition by heavy metals. Doklady biological sciences : proceedings of the Academy of Sciences of the USSR, Biological sciences sections 2016.

Bulletin of experimental biology and medicine · 2016 · PMID 27591879 · BioNex Evolve (PubMed-indexed)

This animal study examined Semax’s effects on sympathetic nerves and blood vessels after experimentally induced heart attacks in rats. Semax moderated sympathetic activation, prevented increased nerve-ending density, and reduced alpha-adrenaline receptors without affecting beta receptors. In isolated tail artery segments after interrupted and restored blood flow, it also reduced responses to electrical stimulation and norepinephrine.

Citation: Gorbacheva AM, Berdalin AB, Stulova AN, Nikogosova AD, Lin MD, Buravkov SV, Gavrilova SA, Koshelev VB. Changes in Sympathetic Innervation of Rat Caudal Artery in Experimental Myocardial Infarction. Effect of Semax Peptide. Bulletin of experimental biology and medicine 2016.

Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova · 2015 · PMID 26356395 · PubMed

This human study compared phenazepam alone with selank plus phenazepam in people with anxiety disorders. The combined treatment produced an earlier therapeutic effect on the HDRS rating scale and reduced several phenazepam side effects during treatment and after withdrawal. The authors reported a positive impact on quality of life.

Citation: Medvedev VE, Tereshchenko ON, Kost NV, Ter-Israelyan AY, Gushanskaya EV, Chobanu IK, Sokolov OY, Myasoedov NF. [Optimization of the treatment of anxiety disorders with selank].. Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova 2015.

Molecular immunology · 2014 · PMID 24291245 · BioNex Evolve (PubMed-indexed)

This animal study examined how Selank and its fragment Gly-Pro affected inflammation-related gene activity in mouse spleens over time. Both peptides altered genes involved in immune responses, often with similar patterns. The researchers suggested that Gly-Pro might contribute to Selank’s overall effect.

Citation: Kolomin T, Morozova M, Volkova A, Shadrina M, Andreeva L, Slominsky P, Limborska S, Myasoedov N. The temporary dynamics of inflammation-related genes expression under tuftsin analog Selank action. Molecular immunology 2014.

Bulletin of experimental biology and medicine · 2014 · PMID 24913576 · BioNex Evolve (PubMed-indexed)

This animal study tested Selank during acute alcohol withdrawal in rats with a history of long-term alcohol consumption. In alcohol-preferring rats, Selank eliminated withdrawal-related anxiety in behavioral tests and prevented pain sensitivity to normally nonpainful mechanical stimulation. It did not affect alcohol consumption.

Citation: Kolik LG, Nadorova AV, Kozlovskaya MM. Efficacy of peptide anxiolytic selank during modeling of withdrawal syndrome in rats with stable alcoholic motivation. Bulletin of experimental biology and medicine 2014.

Doklady biological sciences : proceedings of the Academy of Sciences of the USSR, Biological sciences sections · 2014 · PMID 25371249 · BioNex Evolve (PubMed-indexed)

This animal study examined Selank’s effects on blood clotting, blood fats, and blood sugar in experimental metabolic syndrome. The abstract was not available, so results are not summarized.

Citation: Mjasoedov NF, Andreeva LA, Grigorjeva ME, Obergan TY, Shubina TA, Lyapina LA. The influence of Selank on the parameters of the hemostasis system, lipid profile, and blood sugar level in the course of experimental metabolic syndrome. Doklady biological sciences : proceedings of the Academy of Sciences of the USSR, Biological sciences sections 2014.

BMC genomics · 2014 · PMID 24661604 · BioNex Evolve (PubMed-indexed)

This animal study examined how Semax changed brain gene activity in rats after an artery blockage restricted blood flow. Semax mainly increased activity of immune-related genes and also changed genes involved in blood vessel formation and function. The authors suggested these effects are likely key mechanisms underlying the peptide’s brain-protective effects.

Citation: Medvedeva EV, Dmitrieva VG, Povarova OV, Limborska SA, Skvortsova VI, Myasoedov NF, Dergunova LV. The peptide semax affects the expression of genes related to the immune and vascular systems in rat brain focal ischemia: genome-wide transcriptional analysis. BMC genomics 2014.

Pharmacotherapy · 2014 · PMID 24877185 · PubMed

This analysis used published human cardiovascular trial data to model the relationship between LDL cholesterol and coronary death or nonfatal heart attack. The best-fitting model projected diminishing reductions in these events as LDL cholesterol fell to lower levels. It studied cholesterol and statins, not the Semax peptide.

Citation: Charland SL, Stanek EJ. Sigmoidal maximal effect modeling of low-density lipoprotein cholesterol concentration and annual incidence of coronary heart disease events in secondary prevention trials.. Pharmacotherapy 2014.

Journal of molecular neuroscience : MN · 2013 · PMID 22772900 · BioNex Evolve (PubMed-indexed)

This animal study examined how Semax and its fragment Pro-Gly-Pro affected VEGF-related gene activity after blocked blood flow in rat brains. Both peptides altered Vegf-b and Vegf-d activity in directions opposite to the effects of reduced blood flow. The authors suggest these changes may help lessen the effects of brain ischemia.

Citation: Medvedeva EV, Dmitrieva VG, Povarova OV, Limborska SA, Skvortsova VI, Myasoedov NF, Dergunova LV. Effect of semax and its C-terminal fragment Pro-Gly-Pro on the expression of VEGF family genes and their receptors in experimental focal ischemia of the rat brain. Journal of molecular neuroscience : MN 2013.

Bulletin of experimental biology and medicine · 2012 · PMID 23113251 · BioNex Evolve (PubMed-indexed)

This animal study examined Semax during recovery from stress in rats with different stress tolerance. Semax given before stress reduced the stress-induced increase in macrophage immune cells and tissue damage in active regions of the spleen.

Citation: Bakhmet AA, Koplik EV. Antistress effect of Semax in the course of recovery of spleen lymphoid structures after the stress in rats with different behavioral activity. Bulletin of experimental biology and medicine 2012.

Bulletin of experimental biology and medicine · 2012 · PMID 22803132 · BioNex Evolve (PubMed-indexed)

This animal study examined whether Semax could reduce the later effects of early-life maternal separation in rats. Maternal separation slowed growth and increased activity, emotional reactivity, and anxiety. Semax reduced the impact on body weight and normalized anxiety levels.

Citation: Volodina MA, Sebentsova EA, Glazova NY, Levitskaya NG, Andreeva LA, Manchenko DM, Kamensky AA, Myasoedov NF. Semax attenuates the influence of neonatal maternal deprivation on the behavior of adolescent white rats. Bulletin of experimental biology and medicine 2012.

ClinicalTrials.gov · 2012 · NCT01747200 · ClinicalTrials.gov

This completed human study investigated whether transcranial magnetic stimulation could alter brain rhythms and interfere with recognizing pictures of familiar objects in healthy adults. The abstract describes brain-wave monitoring and recognition tests, but reports no results.

Population / model

Repetitive TMS (rTMS); Sham rTMS; Bilateral rTMS; Unilateral rTMS

Citation: National Institute of Neurological Disorders and Stroke (NINDS). Modulating Behavior in Humans by Entrainment With Rhythmic Transcranial Magnetic Stimulation. ClinicalTrials.gov 2012.

Regulatory peptides · 2011 · PMID 21609736 · BioNex Evolve (PubMed-indexed)

This animal study examined how Selank and its fragments affected inflammation-related gene activity in mouse spleens. They significantly changed the activity of multiple genes, including Bcl6, which is involved in immune system development, and genes it regulates. The findings support Selank’s involvement in regulating inflammation, without establishing whether these changes improve health.

Citation: Kolomin T, Shadrina M, Andreeva L, Slominsky P, Limborska S, Myasoedov N. Expression of inflammation-related genes in mouse spleen under tuftsin analog Selank. Regulatory peptides 2011.

Cellular and molecular neurobiology · 2010 · PMID 19633950 · BioNex Evolve (PubMed-indexed)

This animal study examined Semax and Pro-Gly-Pro in rats after a brain artery was permanently blocked to model stroke. Both peptides increased the activity of genes for nerve-growth proteins and their receptors in the brain's cortex. Semax selectively affected these genes in tissue with reduced blood supply, whereas Pro-Gly-Pro's effects were mainly nonspecific.

Citation: Dmitrieva VG, Povarova OV, Skvortsova VI, Limborska SA, Myasoedov NF, Dergunova LV. Semax and Pro-Gly-Pro activate the transcription of neurotrophins and their receptor genes after cerebral ischemia.. Cellular and molecular neurobiology 2010.

Doklady. Biochemistry and biophysics · 2010 · PMID 20380151 · BioNex Evolve (PubMed-indexed)

This animal study examined changes in gene activity in rat hippocampus and spleen cells after one-time and repeated Selank administration. The abstract was not available, so results are not summarized.

Citation: Kolomin TA, Shadrina MI, Agniullin YV, Shram SI, Slominskii PA, Limborska SA, Myasoedov NF. Transcriptomic response of rat hippocampus and spleen cells to single and chronic administration of the peptide selank. Doklady. Biochemistry and biophysics 2010.

Bulletin of experimental biology and medicine · 2010 · PMID 21113455 · BioNex Evolve (PubMed-indexed)

This animal study examined Semax’s effects on blood-clotting control in rats exposed to acute or chronic immobilization stress. Repeated nasal administration stimulated the body’s anticoagulation system, showing a protective effect against the increased tendency to clot caused by stress.

Citation: Grigorjeva ME, Lyapina LA. Anticoagulation and antiplatelet effects of semax under conditions of acute and chronic immobilization stress. Bulletin of experimental biology and medicine 2010.

Neuroscience and behavioral physiology · 2008 · PMID 18197389 · BioNex Evolve (PubMed-indexed)

This animal study tested Selank in adult rats that had experienced reduced oxygen before birth. Selank improved sensory attention and learning, normalized exploratory behavior, and restored the balance between brain serotonin and noradrenaline systems.

Citation: Semenova TP, Kozlovskaya MM, Zuikov AV, Kozlovskii II, Zakharova NM, Andreeva LA. Use of Selank to correct measures of integrative brain activity and biogenic amine levels in adult rats resulting from antenatal hypoxia. Neuroscience and behavioral physiology 2008.

Doklady biological sciences : proceedings of the Academy of Sciences of the USSR, Biological sciences sections · 2008 · PMID 18841804 · BioNex Evolve (PubMed-indexed)

This animal study examined how Selank administered through the nose regulates expression of BDNF, a protein involved in nerve-cell support, in the rat hippocampus. The abstract was not available, so results are not summarized.

Citation: Inozemtseva LS, Karpenko EA, Dolotov OV, Levitskaya NG, Kamensky AA, Andreeva LA, Grivennikov IA. Intranasal administration of the peptide Selank regulates BDNF expression in the rat hippocampus in vivo. Doklady biological sciences : proceedings of the Academy of Sciences of the USSR, Biological sciences sections 2008.

Restorative neurology and neuroscience · 2008 · PMID 18431004 · BioNex Evolve (PubMed-indexed)

This lab study tested Semax in cultured nerve and support cells from the rat basal forebrain. Semax may increase survival of acetylcholine-producing neurons and increased activity of an enzyme involved in making acetylcholine, without affecting other measured neuron counts or support-cell growth. The relevance to Alzheimer’s disease remains unclear.

Citation: Grivennikov IA, Dolotov OV, Zolotarev YA, Andreeva LA, Myasoedov NF, Leacher L, Black IB, Dreyfus CF. Effects of behaviorally active ACTH (4-10) analogue - Semax on rat basal forebrain cholinergic neurons. Restorative neurology and neuroscience 2008.

Vestnik Rossiiskoi akademii meditsinskikh nauk · 2008 · PMID 19140465 · PubMed

This review discussed theories of emotional stress, brain signaling, and peptides including Semax; the abstract does not specify human or animal study populations. It describes these peptides as factors that increase resistance to stress and emphasizes individual differences in stress tolerance.

Citation: Sudakov KV. [Evolution of the stress concept].. Vestnik Rossiiskoi akademii meditsinskikh nauk 2008.

Bulletin of experimental biology and medicine · 2007 · PMID 18683497 · BioNex Evolve (PubMed-indexed)

This animal study tested Selank’s effects on learning, memory, and attention in adult rats whose brain catecholamine signaling system had been damaged by a neurotoxin early in life. Selank restored cognitive processes disrupted by this experimentally induced damage.

Citation: Semenova TP, Kozlovskaya MM, Zakharova NM, Kozlovskii II, Zuikov AV. Effect of selank on cognitive processes after damage inflicted to the cerebral catecholamine system during early ontogeny. Bulletin of experimental biology and medicine 2007.

Bulletin of experimental biology and medicine · 2007 · PMID 18019011 · BioNex Evolve (PubMed-indexed)

This animal study examined the anti-ulcer effects of Selank and substances formed when it breaks down in the body. The tested peptides reduced the area of experimentally induced stomach ulcers.

Citation: Pavlov TS, Samonina GE, Bakaeva ZV, Zolotarev YA, Guseva AA. Selank and its metabolites maintain homeostasis in the gastric mucosa. Bulletin of experimental biology and medicine 2007.

Neuroscience letters · 2007 · PMID 17353092 · BioNex Evolve (PubMed-indexed)

This animal study examined how Semax affected genes for the nerve-supporting proteins NGF and BDNF in healthy male rats. Semax increased activity of both genes in the hippocampus and increased BDNF gene activity in the brainstem and cerebellum, while reducing NGF gene activity in the frontal cortex. The findings showed rapid changes that differed by gene and brain region.

Citation: Agapova TY, Agniullin YV, Shadrina MI, Shram SI, Slominsky PA, Lymborska SA, Myasoedov NF. Neurotrophin gene expression in rat brain under the action of Semax, an analogue of ACTH 4-10. Neuroscience letters 2007.

Bulletin of experimental biology and medicine · 2007 · PMID 18239779 · BioNex Evolve (PubMed-indexed)

This lab study tested Semax and its Pro-Gly-Pro fragment in cultured nerve cells exposed to toxic glutamate conditions. Both peptides delayed disruption of calcium regulation and loss of mitochondrial electrical potential, and improved cell survival. The findings suggest that Semax's protective effects may involve improved mitochondrial resistance to calcium stress.

Citation: Storozhevykh TP, Tukhbatova GR, Senilova YE, Pinelis VG, Andreeva LA, Myasoyedov NF. Effects of semax and its Pro-Gly-Pro fragment on calcium homeostasis of neurons and their survival under conditions of glutamate toxicity. Bulletin of experimental biology and medicine 2007.

Bulletin of experimental biology and medicine · 2007 · PMID 18018999 · BioNex Evolve (PubMed-indexed)

This animal study compared Semax with the ACTH4-10 peptide fragment in pain-response tests involving rats and mice. Semax reduced pain sensitivity in all experimental models, and the researchers concluded that its structural modification increased pain-relieving potency compared with ACTH4-10.

Citation: Ivanova DM, Levitskaya NG, Andreeva LA, Kamenskii AA, Myasoedov NF. Comparative study of analgesic potency of ACTH4-10 fragment and its analog semax. Bulletin of experimental biology and medicine 2007.

Journal of neurochemistry · 2006 · PMID 16635254 · BioNex Evolve (PubMed-indexed)

This animal and lab study examined Semax binding and levels of brain-derived neurotrophic factor, a protein involved in brain adaptability, in rats. Semax showed specific binding to membranes from the basal forebrain and increased the protein's levels there, but not in the cerebellum. The authors suggested that increased levels might partly explain Semax's cognitive effects.

Citation: Dolotov OV, Karpenko EA, Seredenina TS, Inozemtseva LS, Levitskaya NG, Zolotarev YA, Kamensky AA, Grivennikov IA, Engele J, Myasoedov NF. Semax, an analogue of adrenocorticotropin (4-10), binds specifically and increases levels of brain-derived neurotrophic factor protein in rat basal forebrain.. Journal of neurochemistry 2006.

Bulletin of experimental biology and medicine · 2006 · PMID 17415472 · BioNex Evolve (PubMed-indexed)

This animal and laboratory study tested Selank in mice with drug-induced dopamine-related behaviors and examined receptor binding in rat brain membranes. Selank reduced the behaviors, and naloxone blocked this effect, but Selank did not directly displace compounds bound to the tested dopamine or opioid receptors. The researchers proposed indirect modulation of the body’s opioid system as an explanation.

Citation: Meshavkin VK, Kost NV, Sokolov OY, Zolotarev YA, Myasoedov NF, Zozulya AA. Naloxone-blocked depriming effect of anxiolytic selank on apomorphine-induced behavioral manifestations of hyperfunction of dopamine system. Bulletin of experimental biology and medicine 2006.

Bulletin of experimental biology and medicine · 2006 · PMID 17603664 · BioNex Evolve (PubMed-indexed)

This animal study examined Semax after an experimentally induced loss of blood supply to part of the brain’s prefrontal cortex. Semax reduced the volume of damaged brain tissue and improved memory retention and performance in a learned passive avoidance task.

Citation: Romanova GA, Silachev DN, Shakova FM, Kvashennikova YN, Viktorov IV, Shram SI, Myasoedov NF. Neuroprotective and antiamnesic effects of Semax during experimental ischemic infarction of the cerebral cortex. Bulletin of experimental biology and medicine 2006.

Bulletin of experimental biology and medicine · 2006 · PMID 16984088 · BioNex Evolve (PubMed-indexed)

This animal study tested Semax when dopamine receptors were blocked with haloperidol. Semax had virtually no effect on haloperidol-related disturbances in orientation, exploration, or movement. However, giving Semax beforehand prevented impairment in learning an active avoidance task.

Citation: Sebentsova EA, Levitskaya NG, Andreeva LA, Alfeeva LY, Kamenskii AA, Myasoedov NF. Effects of semax against the background of dopaminergic receptor blockade with haloperidol. Bulletin of experimental biology and medicine 2006.

Brain research · 2006 · PMID 16996037 · BioNex Evolve (PubMed-indexed)

This animal study examined Semax’s effects on learning-related behavior and brain signaling in rats. Semax increased BDNF protein, activation of its receptor trkB, and related gene activity in the hippocampus, while treated rats showed more learned avoidance responses. The researchers suggested that this signaling system may explain Semax’s effects on cognitive function.

Citation: Dolotov OV, Karpenko EA, Inozemtseva LS, Seredenina TS, Levitskaya NG, Rozyczka J, Dubynina EV, Novosadova EV, Andreeva LA, Alfeeva LY, Kamensky AA, Grivennikov IA, Myasoedov NF, Engele J. Semax, an analog of ACTH(4-10) with cognitive effects, regulates BDNF and trkB expression in the rat hippocampus. Brain research 2006.

Neurochemical research · 2005 · PMID 16362768 · BioNex Evolve (PubMed-indexed)

This animal study examined Semax’s effects on dopamine and serotonin systems in rodents’ brains. Semax increased a serotonin breakdown product but did not change dopamine levels on its own. It enhanced the dopamine release and increased movement triggered by amphetamine.

Citation: Eremin KO, Kudrin VS, Saransaari P, Oja SS, Grivennikov IA, Myasoedov NF, Rayevsky KS. Semax, an ACTH(4-10) analogue with nootropic properties, activates dopaminergic and serotoninergic brain systems in rodents.. Neurochemical research 2005.

Bulletin of experimental biology and medicine · 2005 · PMID 16848230 · BioNex Evolve (PubMed-indexed)

This animal study examined seasonal effects of Selank on exploratory behavior in arctic ground squirrels. Selank increased exploration most strongly in spring and fall, with the greatest effect during a seasonal depression-like state. It did not affect overall movement activity.

Citation: Semenova TP, Kozlovskaya MM, Zuikov AV, Kozlovskii II, Andreeva LA. Seasonal effects of Selank on the behavior of hibernating animals. Bulletin of experimental biology and medicine 2005.

Bulletin of experimental biology and medicine · 2005 · PMID 16027870 · BioNex Evolve (PubMed-indexed)

This animal study tested the Semax fragment Pro-Gly-Pro in rats with experimentally reduced blood flow to the brain. The fragment did not affect neurological impairment or mortality. The researchers concluded that Semax’s previously observed neuroprotective effects mainly depend on its ACTH4-7 fragment instead.

Citation: Fadyukova OE, Kadi A, Bai O, Andzhusheva GM, Koshelev VB. C-terminal Pro-Gly-Pro tripeptide in contrast to full-length neuropeptide semax exhibits no neuroprotective effect in experimental cerebral ischemia. Bulletin of experimental biology and medicine 2005.

Doklady biological sciences : proceedings of the Academy of Sciences of the USSR, Biological sciences sections · 2004 · PMID 15508574 · BioNex Evolve (PubMed-indexed)

This animal study explored a new property of Selank, described in the title as a synthetic anti-anxiety compound, and its derivatives. The title does not identify the property or animal species. The abstract was not available, so results are not summarized.

Citation: Pavlov TS, Samonina GE, Andreeva LA, Myasoedov NF, Ashmarin IP. A new property of the synthetic anxiolytic Selank and its derivatives. Doklady biological sciences : proceedings of the Academy of Sciences of the USSR, Biological sciences sections 2004.

Neuroscience and behavioral physiology · 2004 · PMID 15341218 · BioNex Evolve (PubMed-indexed)

This animal study tested Semax in rats with toxin-induced damage to the brain's dopamine system. Semax reduced the severity of behavioral disturbances, including reduced movement and increased anxiety. The researchers suggested that protection may involve effects on dopamine signaling and support for nerve cells.

Citation: Levitskaya NG, Sebentsova EA, Andreeva LA, Alfeeva LY, Kamenskii AA, Myasoedov NF. The neuroprotective effects of Semax in conditions of MPTP-induced lesions of the brain dopaminergic system. Neuroscience and behavioral physiology 2004.

Neuroscience and behavioral physiology · 2003 · PMID 14552529 · BioNex Evolve (PubMed-indexed)

This animal study examined Selank effects on learning and memory in rats with initially poor or normal learning ability using an active avoidance task. Selank significantly improved learning in poor-learning rats, with more correct responses and fewer errors after repeated administration. In normal rats, its strongest learning effects appeared later during repeated training.

Citation: Kozlovskii II, Danchev ND. The optimizing action of the synthetic peptide Selank on a conditioned active avoidance reflex in rats.. Neuroscience and behavioral physiology 2003.

Bulletin of experimental biology and medicine · 2003 · PMID 12802399 · BioNex Evolve (PubMed-indexed)

This lab study tested Semax in cultured rat adrenal tumor cells exposed to oxidative stress from hydrogen peroxide. Semax reduced the number of damaged cells, and its effectiveness depended on when it was added. The authors suggest protection against oxidative damage may contribute to its proposed nerve-protective effects.

Citation: Safarova ER, Shram SI, Zolotarev YA, Myasoedov NF. Effect of Semax peptide on survival of cultured rat pheochromocytoma cells during oxidative stress. Bulletin of experimental biology and medicine 2003.

Bulletin of experimental biology and medicine · 2002 · PMID 12124658 · PubMed

This laboratory study tested cerebrolysin and Semax in cultured rat tumor cells used to study nerve-cell development. Cerebrolysin promoted cell development and survival and reduced programmed cell death, while Semax showed no growth-supporting effect in these cells. The authors suggest that Semax’s protective effects involve other mechanisms.

Citation: Safarova ER, Shram SI, Grivennikov IA, Myasoedov NF. Trophic effects of nootropic peptide preparations cerebrolysin and semax on cultured rat pheochromocytoma.. Bulletin of experimental biology and medicine 2002.

PMID 11245825 · BioNex Evolve (PubMed-indexed)

This animal study tested Semax and glycine in rats with reduced blood flow to the brain, examining nitric oxide production and neurological function. Semax reduced the rise in nitric oxide and restored neurological functioning. Glycine did not reduce nitric oxide levels or improve neurological deficits.

PMID 28255762 · BioNex Evolve (PubMed-indexed)

This animal study examined brain gene activity after Semax or the related peptide PGP in rats with injury caused by blocked brain blood flow. Semax most strongly affected immune-response pathways, while PGP reduced immune activity and nerve-signaling processes. The authors suggest that communication between the nervous and immune systems may explain Semax's protective effects.

PMID 16963804 · BioNex Evolve (PubMed-indexed)

This animal study examined repeated treatment with the tuftsin analogue TP-7 in rats with high emotional reactivity. TP-7 significantly reduced anxiety- and fear-related behavior, and the effects persisted throughout the experiment. It did not change body weight on its own.

PMID 14969422 · BioNex Evolve (PubMed-indexed)

This animal study compared Selank and related tuftsin-family peptides in male rats and mice exposed to a stressful conflict situation. The peptides showed positive emotional and anti-stress effects. Individual effects varied with the peptides' molecular structures or their breakdown products.

ClinicalTrials.gov · 2017 · NCT03031535 · ClinicalTrials.gov

This completed human trial compared a nasal formulation of octreotide with an injected formulation in healthy adults. It assessed safety, tolerability, how the drug enters and leaves the body, and effects on growth hormone and insulin-like growth factor 1; no results are reported.

Population / model

Healthy Volunteer Study

Citation: Dauntless Pharmaceuticals. A Two-Part, Phase 1, Randomized, Crossover Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Intranasal Octreotide (DP1038) Versus Subcutaneous Sandostatin® Injection in Healthy Adult Volunteers. ClinicalTrials.gov 2017.

ClinicalTrials.gov · 2015 · NCT02196831 · ClinicalTrials.gov

This completed human trial was designed to test whether tesamorelin reduces liver fat, inflammation, scarring, and liver cell damage in people with HIV and nonalcoholic fatty liver disease. These were proposed benefits, not reported findings; the abstract provides no results from this trial.

Population / model

Human Immunodeficiency Virus (HIV); Nonalcoholic Fatty Liver Disease (NAFLD); Nonalcoholic Steatohepatitis (NASH)

Citation: Massachusetts General Hospital. Tesamorelin Effects on Liver Fat and Histology in HIV: A Collaborative UO1 Grant. ClinicalTrials.gov 2015.

ClinicalTrials.gov · 2014 · NCT02271282 · ClinicalTrials.gov

This completed human pilot study examined estrogen-receptor blockade in older men and women, focusing on growth hormone and insulin-like growth factor-1. The abstract describes background information and a hypothesis about reduced estrogen activity, but reports no study results.

Population / model

Normal Healthy Volunteers

Citation: Mayo Clinic. Pilot Study of Estradiol-Receptor Blockade in Older Men and Women. ClinicalTrials.gov 2014.

ClinicalTrials.gov · 2011 · NCT01410799 · ClinicalTrials.gov

This registered human trial planned to study whether GHRH could increase growth hormone and improve muscle, bone, and fat tissues in healthy older men and women. Planned assessments included strength, body composition, physical performance, and sugar metabolism. The trial was terminated, and no results are provided.

Population / model

Hormone Deficiency; Aging

Citation: University of Pennsylvania. Three Month Treatment of GHRH (Growth Hormone Releasing Hormone) in the Elderly. ClinicalTrials.gov 2011.

ClinicalTrials.gov · 2008 · NCT00675506 · ClinicalTrials.gov

This registered human trial evaluated synthetic growth hormone-releasing hormone in people with abdominal obesity, focusing on abdominal fat and cardiovascular function. The record lists the trial as completed but provides no results, so whether these outcomes improved is not reported.

Population / model

Abdominal Obesity; Growth Hormone Deficiency

Citation: Massachusetts General Hospital. Physiologic Effects of Long-Term GHRH1-44 in Abdominal Obesity. ClinicalTrials.gov 2008.

Bioconjugate chemistry · 2007 · PMID 17243755 · BioNex Evolve (PubMed-indexed)

This lab and animal study tested a method for attaching the polymer PEG to a specific site on growth hormone-releasing factor. The modified peptide resisted breakdown in rat biological samples and remained in rats’ blood longer, with less distribution to liver and kidneys. It enhanced initial growth hormone release in animals despite reduced activity in lab testing.

Citation: Youn YS, Lee KC. Site-specific PEGylation for high-yield preparation of Lys(21)-amine PEGylated growth hormone-releasing factor (GRF) (1-29) using a GRF(1-29) derivative FMOC-protected at Tyr(1) and Lys(12). Bioconjugate chemistry 2007.

ClinicalTrials.gov · 2007 · NCT00324064 · ClinicalTrials.gov

This completed human study aimed to examine sex differences in growth hormone responses to growth hormone-releasing hormone (GHRH) in healthy people and people with growth hormone deficiency. It also aimed to examine links with cell-signaling proteins, sex hormones, and pubertal development; the abstract lists study aims rather than results.

Population / model

Growth Hormone Deficiency

Citation: Children's Mercy Hospital Kansas City. Sexually Dimorphic Effects of GHRH in Adult Growth Hormone Testing. ClinicalTrials.gov 2007.

ClinicalTrials.gov · 2007 · NCT00608023 · ClinicalTrials.gov

This completed human extension trial assessed the effectiveness and long-term safety of TH9507, a growth hormone-releasing hormone analogue, in people with HIV and excess abdominal fat. The abstract provides no results.

Population / model

Lipodystrophy; HIV Infections

Citation: Theratechnologies. A Multicenter, Double-blind, Randomized, Placebo-controlled Extension Study Assessing the Efficacy and Long-term Safety of a 2 mg Dose of TH9507, a GHRH Analog, in HIV Subjects With Excess Abdominal Fat Accumulation. ClinicalTrials.gov 2007.

ClinicalTrials.gov · 2007 · NCT00807365 · ClinicalTrials.gov

This registered human trial planned to examine whether GHRH could raise growth hormone and improve muscle, bone, and fat tissues in older adults. It also planned to assess how the body processes sugar, fat, and protein. The trial was terminated, and no results are provided.

Population / model

Elderly

Citation: Johns Hopkins University. Six Month Treatment of GHRH in the Elderly. ClinicalTrials.gov 2007.

ClinicalTrials.gov · 2007 · NCT00720902 · ClinicalTrials.gov

This terminated human study planned to compare markers of heart attack and stroke risk in adults with growth hormone deficiency and adults with normal growth hormone secretion. Researchers hypothesized greater cardiovascular risk with deficiency, but the provided abstract reports no results.

Population / model

Growth Hormone Deficiency

Citation: Columbia University. Assessment of Cardiovascular Risk Markers in GH Deficient Patients With Nonsecreting Pituitary Adenomas. ClinicalTrials.gov 2007.

Clinical interventions in aging · 2006 · PMID 18046908 · BioNex Evolve (PubMed-indexed)

This article considers whether sermorelin could offer a better approach to managing growth hormone insufficiency that develops in adults. The abstract was not available, so results are not summarized.

Citation: Walker RF. Sermorelin: a better approach to management of adult-onset growth hormone insufficiency?. Clinical interventions in aging 2006.

ClinicalTrials.gov · 2006 · NCT00257712 · ClinicalTrials.gov

This completed human trial compared growth hormone-releasing hormone (GHRH) with placebo in healthy older adults and older adults with mild cognitive impairment. It examined memory and problem-solving ability, but the abstract reports no results.

Population / model

Aging; Mild Cognitive Impairment

Citation: University of Washington. GHRH: Cognition in Aging and MCI. ClinicalTrials.gov 2006.

Journal of controlled release : official journal of the Controlled Release Society · 2005 · PMID 15987661 · BioNex Evolve (PubMed-indexed)

This lab and animal study examined how GRF(1-29)NH2 interacts with blood proteins and is released from a biodegradable implant in rats. Protein binding caused the peptide to become insoluble, but implants still released it slowly and produced a detectable increase in circulating growth hormone. Combining the peptide with arginine improved its solubility in plasma.

Citation: Mariette B, Coudane J, Vert M. Interactions of GRF(1-29)NH2 with plasma proteins and their effects on the release of the peptide from a PLAGA matrix. Journal of controlled release : official journal of the Controlled Release Society 2005.

ClinicalTrials.gov · 2005 · NCT00123253 · ClinicalTrials.gov

This completed human trial assessed TH9507's effectiveness and safety in people with HIV taking antiretroviral therapy who had excess abdominal fat. The abstract cites an earlier trial showing reduced fat around internal organs and in the trunk, without significant changes in limb fat or fat beneath the skin. It provides no results from the current trial.

Population / model

HIV Infections; Lipodystrophy

Citation: Theratechnologies. A Phase 3 Multicenter, Double-Blind, Randomized, Placebo-Controlled Study Assessing the Efficacy and Safety of a 2 mg Dose of TH9507, a Growth Hormone Releasing Factor Analog, in HIV Patients With Excess of Abdominal Fat Accumulation. ClinicalTrials.gov 2005.

ClinicalTrials.gov · 2004 · NCT01060488 · ClinicalTrials.gov

This registered randomized human trial compared GHRH plus arginine with an insulin tolerance test for diagnosing adult growth hormone deficiency. It included healthy volunteers and people considered likely or unlikely to have the deficiency. The trial is marked completed, but no diagnostic accuracy results are provided.

Population / model

Growth Hormone Deficiency

Citation: Merck KGaA, Darmstadt, Germany. A Phase III, Multicentric, Open-label, Randomised, Comparative, Parallel Group Study of (GHRH + Arginine) Combination Test vs. Insulin Tolerance Test (ITT) in the Diagnosis of Adult Growth Hormone Deficiency (AGHD). ClinicalTrials.gov 2004.

ClinicalTrials.gov · 2004 · NCT00791843 · ClinicalTrials.gov

This completed human trial studied whether synthetic growth hormone-releasing hormone (GHRH) could improve heart structure and function in older adults with congestive heart failure and likely reduced growth hormone effects. Its use for heart failure was investigational, and the provided abstract reports no results.

Population / model

Congestive Heart Failure

Citation: University of Pennsylvania. The Effect of GHRH Therapy on Myocardial Structure and Function in Congestive Heart Failure. ClinicalTrials.gov 2004.

Advanced drug delivery reviews · 2003 · PMID 14499707 · PubMed

This review describes laboratory and animal testing of growth hormone-releasing peptides related to sermorelin, modified by attaching polyethylene glycol to improve stability. Tests included receptor activity in the lab and growth hormone responses in rats and pigs. Some modified peptides retained laboratory activity similar to the unmodified peptide and produced a stronger growth hormone response.

Citation: Esposito P, Barbero L, Caccia P, Caliceti P, D'Antonio M, Piquet G, Veronese FM. PEGylation of growth hormone-releasing hormone (GRF) analogues.. Advanced drug delivery reviews 2003.

ClinicalTrials.gov · 2001 · NCT03018886 · ClinicalTrials.gov

This completed human study aimed to validate a growth hormone-releasing hormone (GHRH) plus arginine test for diagnosing growth hormone deficiency in adults. It also aimed to examine how sex and age affect the test response, but the provided abstract reports no results.

Population / model

Growth Hormone Deficiency

Citation: Helsinki University Central Hospital. Diagnosis of Adult Growth Hormone Deficiency With Growth Hormone Releasing Hormone Plus Arginine Stimulation Test. ClinicalTrials.gov 2001.

European journal of endocrinology · 2000 · PMID 10754477 · PubMed

This randomized human study compared growth hormone responses to GHRH in adult survivors of childhood brain tumors treated with cranial radiation and matched controls. Survivors had reduced growth hormone responses. The authors suggest this may reflect direct pituitary damage, loss of long-term stimulation from GHRH, or both.

Citation: Achermann JC, Brook CG, Hindmarsh PC. The GH response to low-dose bolus growth hormone-releasing hormone (GHRH(1-29)NH2) is attenuated in patients with longstanding post-irradiation GH insufficiency.. European journal of endocrinology 2000.

Clinical endocrinology · 1999 · PMID 10594518 · PubMed

This human study examined growth hormone release in healthy volunteers and survivors of childhood brain tumors treated with cranial radiation. Continuous GHRH increased growth hormone peaks in healthy adults without changing their timing, while combining it with intermittent somatostatin produced regular pulses. Many irradiated survivors also developed more regular release, but their responses remained reduced.

Citation: Achermann JC, Hindmarsh PC, Robinson IC, Matthews DR, Brook CG. The relative roles of continuous growth hormone-releasing hormone (GHRH(1-29)NH2) and intermittent somatostatin(1-14)(SS) in growth hormone (GH) pulse generation: studies in normal and post cranial irradiated individuals.. Clinical endocrinology 1999.

Metabolism: clinical and experimental · 1997 · PMID 9005976 · PubMed

This human trial studied GHRH in healthy older men with low baseline IGF-I, a hormone involved in growth. GHRH increased nighttime growth hormone release, and some strength and endurance measures improved, but IGF-I, body composition, and measured muscle energy responses did not change. No significant adverse effects were observed.

Citation: Vittone J, Blackman MR, Busby-Whitehead J, Tsiao C, Stewart KJ, Tobin J, Stevens T, Bellantoni MF, Rogers MA, Baumann G, Roth J, Harman SM et al.. Effects of single nightly injections of growth hormone-releasing hormone (GHRH 1-29) in healthy elderly men.. Metabolism: clinical and experimental 1997.

The Journal of clinical endocrinology and metabolism · 1997 · PMID 9360512 · PubMed

This randomized, placebo-controlled human trial studied a growth hormone-releasing hormone analog in healthy older men and women. It increased growth hormone secretion and IGF-I levels, alongside increases in some immune cell populations and responses. Total T-cell counts, major T-cell subsets, and natural killer cell counts did not change.

Citation: Khorram O, Yeung M, Vu L, Yen SS. Effects of [norleucine27]growth hormone-releasing hormone (GHRH) (1-29)-NH2 administration on the immune system of aging men and women.. The Journal of clinical endocrinology and metabolism 1997.

Journal of pediatric endocrinology & metabolism : JPEM · 1997 · PMID 9364340 · PubMed

This human study compared growth hormone release after hexarelin or GHRH 1-29 in patients with beta-thalassemia receiving regular transfusions and iron-removal therapy. Hexarelin produced a significantly greater rise in blood growth hormone than GHRH 1-29.

Citation: Tolis G, Karydis I, Markousis V, Karagiorga M, Mesimeris T, Lenaerts V, Deghenghi R. Growth hormone release by the novel GH releasing peptide hexarelin in patients with homozygous beta-thalassemia.. Journal of pediatric endocrinology & metabolism : JPEM 1997.

ClinicalTrials.gov · 1996 · NCT00000380 · ClinicalTrials.gov

This completed human trial examined growth hormone-releasing hormone (GHRH) versus placebo for sleep disturbances in otherwise healthy older men and older women receiving estrogen replacement therapy. The abstract suggests GHRH may help older adults but reports no results from this trial.

Population / model

Sleep Disorders

Citation: University of Washington. Age-Related Sleep Impairment - Treatment w/GHRH. ClinicalTrials.gov 1996.

Hormone research · 1996 · PMID 8950613 · PubMed

This review discusses growth hormone-releasing peptides in human, animal, and laboratory research. Oral GHRP-2 stimulated growth hormone release in children and acted synergistically with growth hormone-releasing hormone. In an animal experiment, GHRP-6 altered gene activity in rat brain regions controlling growth hormone release, although whether its effects were direct remained unclear.

Citation: Argente J, García-Segura LM, Pozo J, Chowen JA. Growth hormone-releasing peptides: clinical and basic aspects.. Hormone research 1996.

The Journal of pharmacy and pharmacology · 1995 · PMID 8583376 · BioNex Evolve (PubMed-indexed)

This laboratory study used rat intestinal tissue preparations to examine the breakdown of GRF(1-29)NH2 and a modified version of the peptide. The enzyme DPP IV was the main source of breakdown at the intestinal cell surface. The modified peptide, designed to resist this enzyme in blood, was also much more stable in intestinal cells.

Citation: Bai JP, Chang LL. The involvement of dipeptidyl peptidase IV in brush-border degradation of GRF(1-29)NH2 by intestinal mucosal cells. The Journal of pharmacy and pharmacology 1995.

The Journal of pediatric endocrinology · 1994 · PMID 7735368 · PubMed

This human study examined repeated GHRH priming in children with short stature and delayed growth who had not responded to an initial GHRH test. Some children developed a stronger growth hormone response after priming, while others did not. The study explored whether this approach could help distinguish hypothalamic from pituitary causes of growth hormone deficiency.

Citation: Bueno G, Bueno M, Garagorri JM, Juste G, Rejas J, Alvarez I. Priming with GHRH (1-29) NH2: an aid in differential diagnosis between hypothalamic and pituitary deficiencies.. The Journal of pediatric endocrinology 1994.

European journal of endocrinology · 1994 · PMID 7921207 · PubMed

This randomized study examined growth hormone responses to a growth hormone-releasing hormone analogue in adult male volunteers. Some tested conditions significantly increased peak growth hormone compared with saline, while another did not. The timing and persistence of the hormone response also differed across conditions.

Citation: Spoudeas HA, Winrow AP, Hindmarsh PC, Brook CG. Low-dose growth hormone-releasing hormone tests: a dose-response study.. European journal of endocrinology 1994.

ClinicalTrials.gov · 1993 · NCT00004332 · ClinicalTrials.gov

This completed human study investigated whether the body's own growth hormone-releasing hormone contributes to stimulated growth hormone release and persistently excessive secretion in patients with acromegaly. The abstract lists study objectives but reports no results.

Population / model

Acromegaly

Citation: National Center for Research Resources (NCRR). Study of the Effect of Growth Hormone-Releasing Hormone Antagonist on Growth Hormone Release in Acromegaly. ClinicalTrials.gov 1993.

Acta paediatrica (Oslo, Norway : 1992). Supplement · 1993 · PMID 8329825 · PubMed

This human study examined how injected or intranasal GHRH was absorbed and stimulated growth hormone release in healthy men. Both routes stimulated growth hormone release, but nasal absorption was low. Responses persisted with repeated intranasal administration, without suppressing growth hormone secretion the following night.

Citation: Wilton P, Chardet Y, Danielson K, Widlund L, Gunnarsson R. Pharmacokinetics of growth hormone-releasing hormone(1-29)-NH2 and stimulation of growth hormone secretion in healthy subjects after intravenous or intranasal administration.. Acta paediatrica (Oslo, Norway : 1992). Supplement 1993.

Neuropeptides · 1991 · PMID 2067598 · BioNex Evolve (PubMed-indexed)

This animal study tested a modified growth hormone-releasing factor on a pain-related withdrawal reflex in rats with surgically altered nervous systems. It specifically blocked reflex enhancement caused by vasoactive intestinal peptide (VIP), but not enhancement caused by several other peptides or skin-nerve stimulation. The authors suggest VIP may not participate in normal transmission of pain signals from the skin.

Citation: Xu XJ, Wiesenfeld-Hallin Z. An analogue of growth hormone releasing factor (GRF), (Ac-Try1, D-Phe2)-GRF-(1-29), specifically antagonizes the facilitation of the flexor reflex induced by intrathecal vasoactive intestinal peptide in rat spinal cord. Neuropeptides 1991.

Canadian journal of physiology and pharmacology · 1991 · PMID 1829020 · BioNex Evolve (PubMed-indexed)

This laboratory study compared natural rat growth hormone-releasing factor with a shorter synthetic version in tests of growth hormone release. Their relative potency differed between testing systems, and prior exposure to the synthetic version reduced later responses to either peptide. The authors suggested that the peptides may act differently at the receptor or in signaling steps within cells.

Citation: Kraicer J, French MB, Lussier BT, Moor BC, Brazlan P. A comparison of the biological activities of authentic rat GRF(1-43)OH with the analogue rat GRF(1-29)NH2. Canadian journal of physiology and pharmacology 1991.

Clinical endocrinology · 1991 · PMID 1934527 · BioNex Evolve (PubMed-indexed)

This human study examined whether clonidine changed growth hormone release during continuous growth hormone-releasing factor infusion in healthy young adults. The infusion increased the size of growth hormone peaks without changing their frequency. Clonidine pretreatment increased overall growth hormone release and peak frequency, with nearly all release occurring within those peaks.

Citation: Lima L, Arce V, Diaz MJ, Tresguerres JA, Devesa J. Clonidine pretreatment modifies the growth hormone secretory pattern induced by short-term continuous GRF infusion in normal man. Clinical endocrinology 1991.

The American journal of physiology · 1990 · PMID 2116730 · BioNex Evolve (PubMed-indexed)

This animal study tested a modified growth hormone-releasing factor that blocks vasoactive intestinal peptide (VIP) activity in anesthetized cats. It reduced widening of colon blood vessels triggered by pelvic nerve stimulation or added VIP. It did not significantly change VIP release, indicating that its effect was not due to reducing release of that peptide.

Citation: Blank MA, Kimura K, Fuortes M, Jaffe BM. VIP antagonist [N-Ac-Tyr1,D-Phe2]-GRF-(1-29)-NH2: an inhibitor of vasodilation in the feline colon. The American journal of physiology 1990.

Methods and findings in experimental and clinical pharmacology · 1990 · PMID 2087150 · BioNex Evolve (PubMed-indexed)

This human study compared short-term memory after growth hormone-releasing factor or placebo in healthy young people. The groups performed similarly before administration, but afterward the peptide group performed better on word-recall tests. The provided abstract is truncated and does not include the authors’ full conclusions.

Citation: Alvarez XA, Cacabelos R. Effects of GRF (1-29) NH2 on short-term memory: neuroendocrine and neuropsychological assessment in healthy young subjects. Methods and findings in experimental and clinical pharmacology 1990.

General and comparative endocrinology · 1990 · PMID 1981568 · BioNex Evolve (PubMed-indexed)

This lab study examined carp growth hormone-releasing factors and somatostatin in cultured rainbow trout pituitary cells. The carp peptides stimulated growth hormone release, while somatostatin inhibited it. Cell density affected the responses, whereas the length of incubation did not.

Citation: Luo DS, McKeown BA, Rivier J, Vale W. In vitro responses of rainbow trout (Oncorhynchus mykiss) somatotrophs to carp growth hormone-releasing factor (GRF) and somatostatin. General and comparative endocrinology 1990.

Journal of steroid biochemistry · 1988 · PMID 2898557 · BioNex Evolve (PubMed-indexed)

This animal study examined the growth hormone response to GRF (1-29) NH2 in female rats treated shortly after birth with estradiol benzoate or testosterone propionate. The abstract was not available, so results are not summarized.

Citation: Aguilar E, López F. GH response to GRF (1-29) NH2 in female rats treated neonatally with estradiol benzoate or testosterone propionate. Journal of steroid biochemistry 1988.

International journal of peptide and protein research · 1988 · PMID 3149952 · BioNex Evolve (PubMed-indexed)

This laboratory and animal study examined newly made ring-shaped analogs of growth hormone-releasing factor and their molecular shapes. Several analogs showed strong biological activity, including in animals, and retained a helical structure. The researchers suggested that maintaining a favorable molecular shape may explain the high activity of one analog.

Citation: Felix AM, Heimer EP, Wang CT, Lambros TJ, Fournier A, Mowles TF, Maines S, Campbell RM, Wegrzynski BB, Toome V. Synthesis, biological activity and conformational analysis of cyclic GRF analogs. International journal of peptide and protein research 1988.

Reproduction, nutrition, developpement · 1987 · PMID 3114840 · BioNex Evolve (PubMed-indexed)

This animal study measured hormone responses to growth hormone-releasing factor (GRF) and thyrotropin-releasing hormone (TRH) in newborn calves. GRF stimulated growth hormone release, while TRH increased growth hormone, prolactin, and thyroid hormones, with some responses differing by age. Neither peptide significantly changed IGF1, insulin, or blood glucose.

Citation: Coxam V, Davicco MJ, Opmeer FA, Ravault JP, Barlet JP. Plasma somatotropin and somatomedin C concentrations following GRF or TRH injections in newborn calves. Reproduction, nutrition, developpement 1987.

Clinical endocrinology · 1986 · PMID 2874906 · BioNex Evolve (PubMed-indexed)

This human study examined whether pirenzepine, which blocks certain nerve-signal receptors, changed growth hormone responses to GRF 1-29 and TRH in people with acromegaly. It did not alter these responses. The findings were consistent with the view that growth hormone-producing pituitary tumors function independently of normal control signals from the hypothalamus.

Citation: Jordan V, Dieguez C, Valcavi R, Artioli C, Portioli I, Rodriguez-Arnao MD, Gomez-Pan A, Hall R, Scanlon MF. Lack of effect of muscarinic cholinergic blockade on the GH responses to GRF 1-29 and TRH in acromegalic subjects. Clinical endocrinology 1986.

Clinical endocrinology · 1986 · PMID 2871952 · BioNex Evolve (PubMed-indexed)

This human study examined how blocking different nerve-signaling pathways or giving thyroid-releasing hormone affected growth hormone release triggered by GRF 1-29. Dopamine and alpha-adrenergic blockade and thyroid-releasing hormone did not change the response, while atropine reduced it. The findings support an important role for acetylcholine-related pathways in regulating growth hormone release.

Citation: Jordan V, Dieguez C, Lafaffian I, Rodriguez-Arnao MD, Gomez-Pan A, Hall R, Scanlon MF. Influence of dopaminergic, adrenergic and cholinergic blockade and TRH administration on GH responses to GRF 1-29. Clinical endocrinology 1986.

Peptides · 1986 · PMID 3018703 · BioNex Evolve (PubMed-indexed)

This lab study tested modified growth hormone-releasing factor peptides in cell membranes from rat pituitary, liver, and pancreas. Different parts of the peptides controlled receptor recognition and activation of a cell-signaling enzyme. Researchers also identified modifications that blocked growth hormone-releasing factor signaling in pituitary membranes or VIP signaling in pancreatic membranes.

Citation: Robberecht P, Waelbroeck M, Coy D, De Neef P, Camus JC, Christophe J. Comparative structural requirements of thirty GRF analogs for interaction with GRF- and VIP receptors and coupling to adenylate cyclase in rat adenopituitary, liver and pancreas. Peptides 1986.

Endocrinology · 1985 · PMID 2994998 · BioNex Evolve (PubMed-indexed)

This laboratory study tested modified growth hormone-releasing factor peptides in rat pituitary tissue preparations. Structural changes altered their ability to activate a signaling enzyme, and one modified peptide competitively blocked the original peptide’s action. This blocker also helped demonstrate that growth hormone-releasing factor and vasoactive intestinal peptide act through distinct receptors in the rat pituitary.

Citation: Robberecht P, Coy DH, Waelbroeck M, Heiman ML, de Neef P, Camus JC, Christophe J. Structural requirements for the activation of rat anterior pituitary adenylate cyclase by growth hormone-releasing factor (GRF): discovery of (N-Ac-Tyr1, D-Arg2)-GRF(1-29)-NH2 as a GRF antagonist on membranes. Endocrinology 1985.

Endocrinology · 1985 · PMID 2859987 · BioNex Evolve (PubMed-indexed)

This laboratory study tested growth hormone-releasing factor and modified versions of it in cell membranes from rat pancreas. The peptides interfered with binding to vasoactive intestinal peptide receptors, and one modified version selectively blocked enzyme activation triggered by either peptide. Other modifications changed receptor binding and signaling activity.

Citation: Waelbroeck M, Robberecht P, Coy DH, Camus JC, De Neef P, Christophe J. Interaction of growth hormone-releasing factor (GRF) and 14 GRF analogs with vasoactive intestinal peptide (VIP) receptors of rat pancreas. Discovery of (N-Ac-Tyr1,D-Phe2)-GRF(1-29)-NH2 as a VIP antagonist. Endocrinology 1985.

Sports Medicine · 2026 · PMID 41966639 · BioNex Evolve (PubMed-indexed)

This review examined peptide safety and effectiveness for musculoskeletal injuries and athletic performance, drawing on animal findings and available human evidence. Many unapproved peptides showed favorable tissue repair and metabolic outcomes in animals, but rigorous human safety data were scarce and there was potential for serious harm.

Citation: Mendias CL, Awan TM. Safety and Efficacy of Approved and Unapproved Peptide Therapies for Musculoskeletal Injuries and Athletic Performance.. Sports Medicine 2026.

The American Journal of Sports Medicine · 2026 · PMID 41476424 · BioNex Evolve (PubMed-indexed)

This review examined injectable peptides for orthopaedic injuries and sports medicine using laboratory, animal, and human research. BPC-157, TB-4, and TB-500 showed tissue-repair potential mainly in preclinical studies, while human evidence was limited or lacking. The authors concluded that evidence remains insufficient to support clinical use and that further safety and effectiveness research is needed.

Citation: Mayfield CK, Bolia IK, Feingold CL, Lin EH, Liu JN, Rick Hatch GF. Injectable Peptide Therapy: A Primer for Orthopaedic and Sports Medicine Physicians.. The American Journal of Sports Medicine 2026.

Joint diseases and related surgery · 2026 · PMID 42542926 · BioNex Evolve (PubMed-indexed)

This animal study tested BPC-157, TB-500, and their combination after Achilles tendon injury and repair in rats. Both peptides were associated with improved tendon tissue organization, but only TB-500 significantly increased the force tendons could withstand before breaking; BPC-157's overall tissue scores were not significantly improved. Combining the peptides provided no additional benefit.

Citation: Biçer O, Adanir O, Güleryüz Y, Balci EC, Dinçel YM, Yenigün MY, Aydin C, Bayrak BY. Effects of BPC-157 and TB-500 on Achilles tendon healing in rats: A histopathological and biomechanical study.. Joint diseases and related surgery 2026.

Journal of chromatography. B, Analytical technologies in the biomedical and life sciences · 2024 · PMID 38382158 · BioNex Evolve (PubMed-indexed)

This animal and laboratory study developed a method to measure TB-500 and its breakdown products in rats, human serum, and enzyme systems, then tested effects in connective-tissue cells. Only the breakdown product Ac-LKKTE significantly improved wound healing compared with controls. The authors suggested that previously reported wound-healing effects may come from this metabolite rather than TB-500 itself.

Citation: Rahaman KA, Muresan AR, Min H, Son J, Han HS, Kang MJ, Kwon OS. Simultaneous quantification of TB-500 and its metabolites in in-vitro experiments and rats by UHPLC-Q-Exactive orbitrap MS/MS and their screening by wound healing activities in-vitro.. Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 2024.

Nature neuroscience · 2024 · PMID 38741020 · PubMed

This animal study examined how the subcommissural organ, a brain gland, supports brain development in mice. Removing its cells during embryonic development caused severe fluid buildup and defects in nerve-cell development. Introducing gland-derived peptides—thymosin beta-4, thymosin beta-10, and NP24—substantially reduced these developmental defects.

Citation: Zhang T, Ai D, Wei P, Xu Y, Bi Z, Ma F, Li F, Chen XJ, Zhang Z, Zou X, Guo Z, Zhao Y et al.. The subcommissural organ regulates brain development via secreted peptides.. Nature neuroscience 2024.

Nature communications · 2023 · PMID 37696839 · PubMed

This animal and lab study examined loss of Sirt1 in blood-vessel lining cells in male mice and its effects on muscle cells. Although vessel function worsened, skeletal muscle insulin sensitivity improved. Increased release of thymosin beta-4 from Sirt1-deficient vessel-lining cells enhanced insulin signaling in muscle cells.

Citation: Li Q, Zhang Q, Kim YR, Gaddam RR, Jacobs JS, Bachschmid MM, Younis T, Zhu Z, Zingman L, London B, Rauckhorst AJ, Taylor EB et al.. Deficiency of endothelial sirtuin1 in mice stimulates skeletal muscle insulin sensitivity by modifying the secretome.. Nature communications 2023.

ClinicalTrials.gov · 2020 · NCT05485818 · ClinicalTrials.gov

This completed randomized human trial studied the efficacy and safety of injectable recombinant human thymosin beta 4 versus placebo in patients with an acute heart attack. The provided abstract describes the study design but reports no efficacy or safety results.

Population / model

Acute Myocardial Infarction

Citation: Beijing Northland Biotech. Co., Ltd.. Phase IIa Clinical Study of Efficacy and Safety of Injectable Recombinant Human Thymosin Beta 4 in Patients With Acute Myocardial Infarction. ClinicalTrials.gov 2020.

ClinicalTrials.gov · 2018 · NCT04555850 · ClinicalTrials.gov

This completed randomized, placebo-controlled human trial studied recombinant human thymosin beta-4 in healthy Chinese volunteers. It aimed to assess safety, tolerability, how the substance moves through the body, and possible immune reactions, but the provided abstract reports no results.

Population / model

Healthy

Citation: Beijing Northland Biotech. Co., Ltd.. A Randomized, Double-blind, Placebo-Controlled, Multiple Doses,Dose-escalation，Phase 1b Study of the Safety, Tolerability，Pharmacokinetics and the Potential Immunological Reaction of Recombinant Human Thymosin Beta4 in Chinese Healthy Volunteers. ClinicalTrials.gov 2018.

Analytical biochemistry · 2017 · PMID 28887173 · BioNex Evolve (PubMed-indexed)

This laboratory study examined how TB-500 and other peptides stick to glass and plastic surfaces used for testing. Products designed to reduce sticking did not improve peptide recovery in every case. The findings indicate that suitable testing materials depend on the peptide’s physical and chemical properties.

Citation: Judák P, Van Eenoo P, Deventer K. Adsorption effects of the doping relevant peptides Insulin Lispro, Synachten, TB-500 and GHRP 5.. Analytical biochemistry 2017.

World journal of gastroenterology · 2017 · PMID 28127198 · PubMed

This animal study tested a modified virus carrying the thymosin beta-4 gene in mice with chemically induced colon inflammation. It reduced colon injury, death of intestinal lining cells, inflammatory-cell buildup, and oxidative stress in both models. The authors concluded that this approach could potentially be developed for inflammatory bowel disease.

Citation: Zheng XY, Lv YF, Li S, Li Q, Zhang QN, Zhang XT, Hao ZM. Recombinant adeno-associated virus carrying thymosin β4 suppresses experimental colitis in mice.. World journal of gastroenterology 2017.

Journal of chromatography. A · 2012 · PMID 23084823 · BioNex Evolve (PubMed-indexed)

This animal and laboratory study developed a method to detect TB-500 and its breakdown products in horse urine and blood plasma for doping control. The method successfully confirmed these substances in samples from horses given TB-500. The study evaluated detection, not healing or other health benefits.

Citation: Ho EN, Kwok WH, Lau MY, Wong AS, Wan TS, Lam KK, Schiff PJ, Stewart BD. Doping control analysis of TB-500, a synthetic version of an active region of thymosin β₄, in equine urine and plasma by liquid chromatography-mass spectrometry.. Journal of chromatography. A 2012.

Diabetes research and clinical practice · 2012 · PMID 22217673 · PubMed

This animal study tested thymosin beta 4 in mice with a model of type 2 diabetes. It improved glucose tolerance and insulin resistance, reduced a marker of long-term blood sugar and triglycerides, and increased adiponectin. These findings were observed in mice, not established in humans.

Citation: Zhu J, Su LP, Ye L, Lee KO, Ma JH. Thymosin beta 4 ameliorates hyperglycemia and improves insulin resistance of KK Cg-Ay/J mouse.. Diabetes research and clinical practice 2012.

ClinicalTrials.gov · 2008 · NCT00743769 · ClinicalTrials.gov

This registered human trial planned to compare intravenous thymosin beta-4 with placebo in healthy volunteers, assessing safety, tolerability, and how it moves through the body. The trial was withdrawn, and the provided abstract reports no results.

Population / model

Myocardial Infarction; Myocardial Ischemia

Citation: RegeneRx Biopharmaceuticals, Inc.. A Randomized, Double-Blind, Placebo-Controlled, Dose-Response Phase 1 Study of the Safety and Tolerability of the Intravenous Administration of Thymosin Beta 4 and Its Pharmacokinetics After Single and Multiple Doses in Healthy Volunteers. ClinicalTrials.gov 2008.

Annals of the New York Academy of Sciences · 2007 · PMID 17495248 · PubMed

This review discusses lab research on how beta-thymosins affect actin, a protein that helps cells maintain shape and move. Some cellular effects fit their role in binding individual actin units, while others do not. The authors suggest these varied effects may also involve indirect changes to cell structure and signaling pathways.

Citation: Sun HQ, Yin HL. The beta-thymosin enigma.. Annals of the New York Academy of Sciences 2007.

ClinicalTrials.gov · 2006 · NCT00382174 · ClinicalTrials.gov

This completed randomized, placebo-controlled human trial evaluated thymosin beta-4 applied to the skin in patients with pressure ulcers. It aimed to assess safety, tolerability, and effectiveness, but the provided abstract reports no results.

Population / model

Pressure Ulcers

Citation: RegeneRx Biopharmaceuticals, Inc.. A Randomized, Double-Blind, Placebo-Controlled, Dose Response Study of the Safety and Efficacy of Thymosin Beta 4 in the Treatment of Patients With Pressure Ulcers. ClinicalTrials.gov 2006.

Cell proliferation · 1995 · PMID 7534483 · PubMed

This lab study examined thymosin beta-4 messenger RNA in cultured mouse cells as they resumed growth or progressed through cell division. Its levels rose when resting cells began proliferating but did not vary across stages in already-dividing cells. The authors concluded that the gene is regulated by cell proliferation rather than by the cell-cycle stage.

Citation: Zalvide JB, Alvarez CV, Vidal A, Dieguez C, Vega FV, Domínguez F. Regulation of thymosin beta 4 mRNA levels during cell proliferation.. Cell proliferation 1995.

The Journal of biological chemistry · 1993 · PMID 8416954 · PubMed

This lab study used thymosin beta-4 and thymosin beta-10 produced in bacteria to examine their interactions with skeletal muscle actin. Both bound individual actin units and similarly inhibited their assembly into filaments. The authors concluded that both primarily hold actin units apart, although some interactions remain incompletely understood.

Citation: Yu FX, Lin SC, Morrison-Bogorad M, Atkinson MA, Yin HL. Thymosin beta 10 and thymosin beta 4 are both actin monomer sequestering proteins.. The Journal of biological chemistry 1993.

The Journal of biological chemistry · 1982 · PMID 7054160 · PubMed

This animal and lab study isolated thymosin beta-4, established its amino acid sequence, and examined its biological activity. It induced expression of a DNA-related enzyme in mouse thymus cells, both in animals and in the lab, and inhibited movement of macrophages, a type of immune cell.

Citation: Low TL, Goldstein AL. Chemical characterization of thymosin beta 4.. The Journal of biological chemistry 1982.

BMJ open · 2026 · PMID 42419889 · BioNex Evolve (PubMed-indexed)

This protocol describes a registered randomized human trial testing tesamorelin plus exercise versus placebo plus exercise in sedentary older adults living with HIV who have excess abdominal fat and frailty or risk of frailty. The trial will assess physical function, muscle health, quality of life, and exercise adherence. No results are reported.

Citation: Erlandson KM, Gustafson L, Johnson JE, Kulik GL, Khuu V, Chahal N, Walpert AR, Galdamez ME, Zorgno I, Foldyna B, Jarraya M, Reusch JE, Lee H, Grinspoon SK, Jankowski CM, Fourman LT. Tesamorelin as an Adjunct to Exercise for Improving Physical Function in HIV (TRIUMPH): a clinical trial protocol. BMJ open 2026.

Obesity research & clinical practice · 2026 · PMID 41545261 · BioNex Evolve (PubMed-indexed)

This meta-analysis examined randomized trials of tesamorelin in adults with HIV-associated changes in body fat distribution. Tesamorelin was associated with reduced deep abdominal, trunk, limb, and liver fat and increased lean body mass, but no significant reduction in fat under the skin or body mass index. Reported side effects included joint and muscle pain, tingling, and injection-site reactions.

Citation: Badran AS, Helal A, Shata KS, Ayesh H. Body composition, hepatic fat, metabolic, and safety outcomes of Tesamorelin, a GHRH analogue, in HIV-associated lipodystrophy: A meta-analysis of randomized controlled trials. Obesity research & clinical practice 2026.

Journal of the International Association of Providers of AIDS Care · 2026 · PMID 42538058 · BioNex Evolve (PubMed-indexed)

This systematic review combined randomized trials of tesamorelin in people with HIV and treatment-associated changes in body fat distribution. Tesamorelin reduced deep abdominal fat, waist size, and trunk fat, increased lean body mass, and modestly improved cholesterol. Growth hormone-related side effects and more treatment discontinuations were observed, while long-term safety and durability of benefits remain uncertain.

Citation: Ditta AM, Naeem RM, Sami MM, Abdul Rafey M, Ali H, Amjad MW, Jahangir F, Rizvi KA, Mohammad F, Abu Dawood H, Suleman M, Saddique MN. Efficacy and Safety of Tesamorelin in People Living With HIV (PLWH) With Lipodystrophy: A Systematic Review and Meta-Analysis. Journal of the International Association of Providers of AIDS Care 2026.

Journal of clinical medicine · 2026 · PMID 41598480 · PubMed

This review examined human research on drugs intended to preserve muscle and other lean tissue during weight loss in people with overweight or obesity; animal studies were excluded. Weight loss was accompanied by lean tissue loss across methods, and several drug classes, including tesamorelin, were being explored. Most remained in early development, with some showing promise.

Citation: Arora G, Conde KR, Desouza CV. Pharmacologic Treatments for the Preservation of Lean Body Mass During Weight Loss.. Journal of clinical medicine 2026.

ClinicalTrials.gov · 2026 · NCT07481734 · ClinicalTrials.gov

This recruiting, randomized, placebo-controlled human trial is evaluating whether tesamorelin reduces liver fat in adults with metabolic dysfunction-associated fatty liver disease. Researchers will measure liver fat using MRI and monitor blood sugar and IGF-1 for safety. The trial is ongoing, and no results are reported.

Population / model

Metabolic Associated Steatotic Liver Disease; Nonalcoholic Steatohepatitis; Hepatic Steatosis

Citation: Hudson Biotech. A Randomized, Double-Blind, Placebo-Controlled Phase II Study of Tesamorelin (GHRH Analog) for Reducing Hepatic Steatosis in Adults With Metabolic Associated Steatotic Liver Disease (MASLD). ClinicalTrials.gov 2026.

The Journal of infectious diseases · 2025 · PMID 39813152 · BioNex Evolve (PubMed-indexed)

This randomized, open-label trial compared tesamorelin with standard care in people with suppressed HIV, abdominal obesity, and cognitive impairment. Tesamorelin reduced waist circumference more than standard care, but cognitive improvement did not differ significantly between groups. Limited statistical power and the absence of a placebo group restricted the conclusions.

Citation: Ellis RJ, Vaida F, Hu K, Dube M, Henry B, Chow F, Heaton RK, Lee D, Sattler F. Effects of Tesamorelin on Neurocognitive Impairment in Persons With HIV and Abdominal Obesity.. The Journal of infectious diseases 2025.

Current opinion in HIV and AIDS · 2025 · PMID 40397552 · PubMed

This review examined metabolic dysfunction-associated fatty liver disease in people with HIV. It reports a more aggressive disease course than in people without HIV, with HIV-related factors worsening progression. Studies of tesamorelin and GLP-1 receptor agonists have shown promise, but research evaluating therapies specifically in people with HIV remains limited.

Citation: Gattu AK, Fourman LT. Metabolic dysfunction-associated steatotic liver disease in people with HIV.. Current opinion in HIV and AIDS 2025.

AIDS (London, England) · 2024 · PMID 38905488 · BioNex Evolve (PubMed-indexed)

This analysis of a randomized human trial studied tesamorelin in people with HIV and fatty liver disease who were taking integrase inhibitors. Compared with placebo, tesamorelin significantly reduced fat around internal organs, liver fat, and the ratio of trunk to limb fat. It was well tolerated, with similar adverse-event rates and no worsening of blood sugar control.

Citation: Russo SC, Ockene MW, Arpante AK, Johnson JE, Lee H, Toribio M, Stanley TL, Hadigan CM, Grinspoon SK, Erlandson KM, Fourman LT. Efficacy and safety of tesamorelin in people with HIV on integrase inhibitors. AIDS (London, England) 2024.

Topics in antiviral medicine · 2024 · PMID 39746672 · PubMed

This review summarized conference findings on brain and mental health complications in people with HIV. Reports included evidence of ongoing HIV genetic activity in brain and spinal fluid cells despite virus-suppressing treatment, alongside links to vascular disease, genetic risk, and aging. Tesamorelin trials were discussed, but the abstract does not state their results.

Citation: Corley MJ, Letendre SL, Nightingale S. CROI 2024: Neuropsychiatric Complications in People With HIV.. Topics in antiviral medicine 2024.

AIDS (London, England) · 2021 · PMID 33756511 · BioNex Evolve (PubMed-indexed)

This analysis used completed human trials to compare tesamorelin responders with placebo recipients among people living with HIV and excess abdominal fat. In responders, fat density on CT scans increased both around internal organs and under the skin, independently of changes in fat quantity. The findings suggest improved fat quality in this selected group.

Citation: Lake JE, La K, Erlandson KM, Adrian S, Yenokyan G, Scherzinger A, Dubé MP, Stanley T, Grinspoon S, Falutz J, Mamputu JC, Marsolais C. Tesamorelin improves fat quality independent of changes in fat quantity.. AIDS (London, England) 2021.

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2021 · PMID 33852720 · PubMed

This randomized, placebo-controlled human trial examined tesamorelin in people with HIV and nonalcoholic fatty liver disease. Tesamorelin reduced blood markers related to immune cell activation and reduced activity in immune-related pathways in liver tissue. These findings suggest that increasing growth hormone activity may lessen immune activation in this population.

Citation: Stanley TL, Fourman LT, Wong LP, Sadreyev R, Billingsley JM, Feldpausch MN, Zheng I, Pan CS, Boutin A, Lee H, Corey KE, Torriani M et al.. Growth Hormone Releasing Hormone Reduces Circulating Markers of Immune Activation in Parallel with Effects on Hepatic Immune Pathways in Individuals with HIV-infection and Nonalcoholic Fatty Liver Disease.. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 2021.

Drug design, development and therapy · 2021 · PMID 34588764 · PubMed

This review examined drugs being developed for people with nonalcoholic steatohepatitis, a fatty liver disease involving chronic inflammation. It concluded that the disease's complexity makes a single therapy challenging and that combinations targeting different mechanisms will likely be needed. At publication, tesamorelin was expected to enter late-stage human trials; the abstract gives no tesamorelin results.

Citation: Fraile JM, Palliyil S, Barelle C, Porter AJ, Kovaleva M. Non-Alcoholic Steatohepatitis (NASH) - A Review of a Crowded Clinical Landscape, Driven by a Complex Disease.. Drug design, development and therapy 2021.

JCI insight · 2020 · PMID 32701508 · BioNex Evolve (PubMed-indexed)

Researchers analyzed liver biopsies from a randomized tesamorelin trial in people with HIV and nonalcoholic fatty liver disease. Tesamorelin increased activity of genes involved in cellular energy production and decreased activity of genes involved in inflammation, tissue repair, and cell division. These changes correlated with an improved gene-based score related to liver scarring.

Citation: Fourman LT, Billingsley JM, Agyapong G, Ho Sui SJ, Feldpausch MN, Purdy J, Zheng I, Pan CS, Corey KE, Torriani M, Kleiner DE, Hadigan CM, Stanley TL, Chung RT, Grinspoon SK. Effects of tesamorelin on hepatic transcriptomic signatures in HIV-associated NAFLD. JCI insight 2020.

The lancet. HIV · 2019 · PMID 31611038 · BioNex Evolve (PubMed-indexed)

This randomized human trial compared tesamorelin with placebo in people with HIV and non-alcoholic fatty liver disease. Tesamorelin reduced liver fat more than placebo, without differences in blood sugar changes, but caused more localized injection-site complaints, none considered serious. The authors concluded it might be beneficial, while longer-term effects on liver tissue need further study.

Citation: Stanley TL, Fourman LT, Feldpausch MN, Purdy J, Zheng I, Pan CS, Aepfelbacher J, Buckless C, Tsao A, Kellogg A, Branch K, Lee H, Liu CY, Corey KE, Chung RT, Torriani M, Kleiner DE, Hadigan CM, Grinspoon SK. Effects of tesamorelin on non-alcoholic fatty liver disease in HIV: a randomised, double-blind, multicentre trial. The lancet. HIV 2019.

The Journal of frailty & aging · 2019 · PMID 31237318 · BioNex Evolve (PubMed-indexed)

This exploratory analysis of human trials examined trunk muscles in adults with HIV and abdominal obesity. Among tesamorelin recipients whose internal abdominal fat decreased meaningfully, tesamorelin was associated with greater increases in muscle density and muscle area than placebo. Long-term effects and the impact on daily life need further study.

Citation: Adrian S, Scherzinger A, Sanyal A, Lake JE, Falutz J, Dubé MP, Stanley T, Grinspoon S, Mamputu JC, Marsolais C, Brown TT, Erlandson KM. The Growth Hormone Releasing Hormone Analogue, Tesamorelin, Decreases Muscle Fat and Increases Muscle Area in Adults with HIV. The Journal of frailty & aging 2019.

ClinicalTrials.gov · 2018 · NCT03150511 · ClinicalTrials.gov

This recruiting human trial is comparing tesamorelin with no treatment after surgical repair of upper-limb peripheral nerve injuries. Researchers will assess nerve regrowth, muscle function, and sensation to test whether tesamorelin improves recovery. The trial is ongoing, and no results are reported.

Population / model

Peripheral Nerve Injuries

Citation: Johns Hopkins University. Tesamorelin Therapy to Enhance Axonal Regeneration, Minimize Muscle Atrophy, and Improve Functional Outcomes Following Peripheral Nerve Injury. ClinicalTrials.gov 2018.

ClinicalTrials.gov · 2018 · NCT03226821 · ClinicalTrials.gov

This human trial planned to examine tesamorelin’s effects on body composition, fat tissue, metabolism, and insulin sensitivity in people with HIV-related changes in fat distribution and excess abdominal fat. The trial was terminated, and no results are reported.

Population / model

HIV Lipodystrophy Syndrome; Growth Hormone Deficiency; Body Composition

Citation: Columbia University. Body Composition and Adipose Tissue in HIV Lipodystrophy: Effects of Tesamorelin Therapy. ClinicalTrials.gov 2018.

PloS one · 2017 · PMID 28617838 · BioNex Evolve (PubMed-indexed)

This randomized, placebo-controlled human trial examined whether tesamorelin affected insulin response and blood sugar control in people with type 2 diabetes. Neither insulin response nor overall diabetes control differed significantly between groups. Total cholesterol and cholesterol outside the HDL category decreased significantly in one tesamorelin group compared with placebo.

Citation: Clemmons DR, Miller S, Mamputu JC. Safety and metabolic effects of tesamorelin, a growth hormone-releasing factor analogue, in patients with type 2 diabetes: A randomized, placebo-controlled trial. PloS one 2017.

ClinicalTrials.gov · 2017 · NCT02572323 · ClinicalTrials.gov

This completed human trial tested whether tesamorelin combined with a text-messaging application to support motivation and adherence could improve memory and thinking in older people with HIV. The abstract states the study aim but reports no results.

Population / model

Mild Cognitive Impairment

Citation: University of California, San Diego. Phase II Trial of Tesamorelin for Cognition in Aging HIV-Infected Persons. ClinicalTrials.gov 2017.

Best practice & research. Clinical endocrinology & metabolism · 2017 · PMID 28477736 · PubMed

This review examined growth hormone function in people with HIV, especially those with abnormal body fat distribution. Growth hormone release was reduced, although the underlying causes remain complex and incompletely understood. The review reports that tesamorelin is effective in reducing fat around internal organs in people with HIV-related fat redistribution.

Citation: Rochira V, Guaraldi G. Growth hormone deficiency and human immunodeficiency virus.. Best practice & research. Clinical endocrinology & metabolism 2017.

Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society · 2017 · PMID 29031905 · PubMed

This randomized, placebo-controlled human trial examined the hormone FGF21 during tesamorelin treatment in people with HIV and excess abdominal fat. FGF21 tended to decrease with tesamorelin, but the difference from placebo was not statistically significant. Across participants, FGF21 reductions were associated with reduced liver fat and improved liver-related markers, suggesting tesamorelin reduces liver fat through pathways other than increasing FGF21.

Citation: Braun LR, Feldpausch MN, Czerwonka N, Torriani M, Grinspoon SK, Stanley TL. Fibroblast growth factor 21 decreases after liver fat reduction via growth hormone augmentation.. Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society 2017.

2016 · PMID 30896905 · BioNex Evolve (PubMed-indexed)

This report reviews economic aspects of tesamorelin, also called Egrifta. The abstract was not available, so results are not summarized.

2016 · PMID 30920787 · BioNex Evolve (PubMed-indexed)

The title identifies a clinical review report on tesamorelin, also called Egrifta, without specifying a patient population. The abstract was not available, so results are not summarized.

2016 · PMID 30896908 · BioNex Evolve (PubMed-indexed)

The title identifies a Canadian Drug Expert Committee final recommendation concerning tesamorelin (Egrifta) for HIV-associated excess fat accumulation. The abstract was not available, so results are not summarized.

ClinicalTrials.gov · 2016 · NCT02931474 · ClinicalTrials.gov

This human trial planned to compare growth hormone-releasing hormone with placebo for sleep and hormone regulation in service members and veterans with traumatic brain injury and insomnia. The trial was withdrawn, and no results are reported.

Population / model

Sleep Disorder; Traumatic Brain Injury

Citation: National Institute of Nursing Research (NINR). The Impact of GHRH on Sleep Promotion and Endocrine Regulation in Service Members Who Sustained a Traumatic Brain Injury and Have Current Insomnia. ClinicalTrials.gov 2016.

Clinical pharmacokinetics · 2015 · PMID 25358450 · BioNex Evolve (PubMed-indexed)

This human study modeled how tesamorelin is absorbed and cleared in people with HIV and healthy participants. The model described blood concentrations in both groups, and one component of absorption increased over time. No clinically relevant predictors of tesamorelin's behavior in the body were identified among the characteristics studied.

Citation: González-Sales M, Barrière O, Tremblay PO, Nekka F, Mamputu JC, Boudreault S, Tanguay M. Population pharmacokinetic analysis of tesamorelin in HIV-infected patients and healthy subjects. Clinical pharmacokinetics 2015.

Journal of pharmacokinetics and pharmacodynamics · 2015 · PMID 25895899 · BioNex Evolve (PubMed-indexed)

This analysis used early-stage human trial data from people with HIV and healthy volunteers to model growth hormone and insulin-like growth factor responses to tesamorelin. The model accurately predicted changes in these hormones over time. Within the ranges studied, participant characteristics such as age, sex, and health status were not significantly associated with the model parameters.

Citation: González-Sales M, Barrière O, Tremblay PO, Nekka F, Mamputu JC, Boudreault S, Tanguay M. Population pharmacokinetic and pharmacodynamic analysis of tesamorelin in HIV-infected patients and healthy subjects. Journal of pharmacokinetics and pharmacodynamics 2015.

PloS one · 2015 · PMID 26457580 · BioNex Evolve (PubMed-indexed)

This analysis of human trials examined predictors of deep abdominal fat reduction with tesamorelin in people with HIV and excess abdominal fat. Participants with metabolic syndrome, elevated triglycerides, or white race were most likely to experience reductions. Tesamorelin recipients were more likely than placebo recipients to reach a fat threshold associated with lower health risk.

Citation: Mangili A, Falutz J, Mamputu JC, Stepanians M, Hayward B. Predictors of Treatment Response to Tesamorelin, a Growth Hormone-Releasing Factor Analog, in HIV-Infected Patients with Excess Abdominal Fat. PloS one 2015.

ClinicalTrials.gov · 2015 · NCT02196831 · ClinicalTrials.gov

This completed human trial was designed to test whether tesamorelin reduces liver fat, inflammation, scarring, and liver cell damage in people with HIV and nonalcoholic fatty liver disease. These were proposed benefits, not reported findings; the abstract provides no results from this trial.

Population / model

Human Immunodeficiency Virus (HIV); Nonalcoholic Fatty Liver Disease (NAFLD); Nonalcoholic Steatohepatitis (NASH)

Citation: Massachusetts General Hospital. Tesamorelin Effects on Liver Fat and Histology in HIV: A Collaborative UO1 Grant. ClinicalTrials.gov 2015.

The Journal of clinical endocrinology and metabolism · 2014 · PMID 24178787 · BioNex Evolve (PubMed-indexed)

This placebo-controlled human trial studied tesamorelin in adults with obesity and reduced growth hormone secretion, measuring muscle energy recovery after exercise. Tesamorelin increased the growth-related hormone IGF-I more than placebo. Increases in IGF-I were associated with improved muscle energy recovery, suggesting improved function of the cells' energy-producing mitochondria.

Citation: Makimura H, Murphy CA, Feldpausch MN, Grinspoon SK. The effects of tesamorelin on phosphocreatine recovery in obese subjects with reduced GH. The Journal of clinical endocrinology and metabolism 2014.

JAMA · 2014 · PMID 25038357 · BioNex Evolve (PubMed-indexed)

This randomized trial studied tesamorelin in adults with HIV and excess abdominal fat who were receiving antiretroviral treatment. Tesamorelin was associated with reduced fat around internal organs and modest reductions in liver fat compared with placebo. Further studies are needed to determine the clinical importance and long-term consequences.

Citation: Stanley TL, Feldpausch MN, Oh J, Branch KL, Lee H, Torriani M, Grinspoon SK. Effect of tesamorelin on visceral fat and liver fat in HIV-infected patients with abdominal fat accumulation: a randomized clinical trial. JAMA 2014.

Best practice & research. Clinical endocrinology & metabolism · 2013 · PMID 24054930 · PubMed

This review examined increasing growth hormone activity in older adults, emphasizing men. Limited controlled studies suggested that growth hormone increased lean mass and reduced fat, but there was little evidence of improved strength, physical performance, or quality of life. The review reports that tesamorelin restored normal growth hormone release patterns, reduced internal abdominal fat, artery wall thickness, and triglycerides, and improved cognition in older people.

Citation: Sattler FR. Growth hormone in the aging male.. Best practice & research. Clinical endocrinology & metabolism 2013.

ClinicalTrials.gov · 2013 · NCT01579695 · ClinicalTrials.gov

This observational human study planned to assess long-term safety concerns by comparing people with HIV and excess abdominal fat who received tesamorelin with similar people who did not. The study was terminated, and no results are reported.

Population / model

HIV

Citation: Theratechnologies. A Phase 4, Observational, Multicenter, 10-year Prospective Cohort Safety Study Comparing Subjects With HIV-associated Abdominal Lipohypertrophy Exposed to EGRIFTA® (Tesamorelin for Injection) to a Similar Group of Subjects Not Exposed to EGRIFTA®. ClinicalTrials.gov 2013.

The Annals of pharmacotherapy · 2012 · PMID 22298602 · BioNex Evolve (PubMed-indexed)

This review examined human trials of tesamorelin for HIV-associated lipodystrophy, a condition involving abnormal body fat distribution. Tesamorelin reduced waist size and fat around internal organs and improved some body image measures, with improvements maintained during continued treatment. The review noted limited long-term safety and adherence data.

Citation: Spooner LM, Olin JL. Tesamorelin: a growth hormone-releasing factor analogue for HIV-associated lipodystrophy.. The Annals of pharmacotherapy 2012.

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2012 · PMID 22495074 · BioNex Evolve (PubMed-indexed)

This analysis of randomized human trials examined whether loss of fat around internal organs was linked to metabolic changes in people with HIV receiving tesamorelin. Compared with nonresponders, those with substantial fat loss had improved triglyceride and adiponectin levels and better preservation of blood sugar regulation. These metabolic changes were associated with the reduction in internal abdominal fat.

Citation: Stanley TL, Falutz J, Marsolais C, Morin J, Soulban G, Mamputu JC, Assaad H, Turner R, Grinspoon SK. Reduction in visceral adiposity is associated with an improved metabolic profile in HIV-infected patients receiving tesamorelin. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 2012.

The Journal of clinical endocrinology and metabolism · 2012 · PMID 23015655 · PubMed

This randomized, placebo-controlled human trial studied tesamorelin in adults with abdominal obesity and reduced growth hormone release. Tesamorelin reduced fat around internal organs and improved triglycerides, an inflammation marker, and neck artery wall thickness, without significantly changing fat under the skin or worsening blood sugar. No serious adverse events or differences in adverse events between groups were reported.

Citation: Makimura H, Feldpausch MN, Rope AM, Hemphill LC, Torriani M, Lee H, Grinspoon SK. Metabolic effects of a growth hormone-releasing factor in obese subjects with reduced growth hormone secretion: a randomized controlled trial.. The Journal of clinical endocrinology and metabolism 2012.

Archives of neurology · 2012 · PMID 22869065 · PubMed

This randomized, placebo-controlled human trial studied tesamorelin in healthy older adults and adults with mild cognitive impairment. It found favorable effects on cognition in both groups, particularly skills involved in planning and managing tasks; verbal memory showed a trend toward benefit. Adverse events were mild but more common with tesamorelin, and longer trials are needed.

Citation: Baker LD, Barsness SM, Borson S, Merriam GR, Friedman SD, Craft S, Vitiello MV. Effects of growth hormone–releasing hormone on cognitive function in adults with mild cognitive impairment and healthy older adults: results of a controlled trial.. Archives of neurology 2012.

Annales d'endocrinologie · 2012 · PMID 22748602 · PubMed

This review examined human lipodystrophy syndromes, which involve loss of body fat and sometimes fat buildup elsewhere. It described inherited and acquired forms and their links to insulin resistance, diabetes, and cardiovascular complications. The review reports tesamorelin as effective for metabolic syndrome in people with HIV, without detailing specific outcomes in the abstract.

Citation: Vantyghem MC, Balavoine AS, Douillard C, Defrance F, Dieudonne L, Mouton F, Lemaire C, Bertrand-Escouflaire N, Bourdelle-Hego MF, Devemy F, Evrard A, Gheerbrand D et al.. How to diagnose a lipodystrophy syndrome.. Annales d'endocrinologie 2012.

ClinicalTrials.gov · 2012 · NCT01591902 · ClinicalTrials.gov

This randomized, placebo-controlled human trial was designed to assess whether tesamorelin increased the risk of developing or worsening diabetes-related eye damage in people with HIV, excess abdominal fat, and type 2 diabetes. The trial was terminated, and the provided record reports no results.

Population / model

Diabetic Retinopathy; HIV

Citation: Theratechnologies. A Prospective, Randomized, Placebo-controlled, Double-blind Clinical Trial to Evaluate Whether EGRIFTA® (Tesamorelin for Injection), 2 mg Once Daily SC, Increases the Risk of Development or Progression of Diabetic Retinopathy When Administered to HIV-infected Subjects With Abdominal Lipohypertrophy and Concomitant Diabetes. ClinicalTrials.gov 2012.

ClinicalTrials.gov · 2012 · NCT01788462 · ClinicalTrials.gov

This planned human study aimed to examine whether tesamorelin affects sleep apnea severity and upper-airway muscle responses in people with HIV and excess abdominal fat. The study was withdrawn, and no results are reported.

Population / model

Lipodystrophy

Citation: Johns Hopkins University. Egrifta Replacement and Sleep Disordered Breathing. ClinicalTrials.gov 2012.

Nature reviews. Drug discovery · 2011 · PMID 21283099 · BioNex Evolve (PubMed-indexed)

This record describes tesamorelin, a growth hormone-releasing factor analogue, in the context of excess abdominal fat in people with HIV and abnormal fat distribution. The abstract does not describe an animal experiment or report study methods or findings.

Citation: Grunfeld C, Dritselis A, Kirkpatrick P. Tesamorelin.. Nature reviews. Drug discovery 2011.

Drugs · 2011 · PMID 21668043 · BioNex Evolve (PubMed-indexed)

This review examined tesamorelin in human trials involving people with HIV-associated abdominal fat accumulation. Tesamorelin reduced fat around internal organs without a clinically significant effect on fat beneath the skin; internal abdominal fat returned after treatment stopped. It was generally well tolerated, but the review noted that longer-term experience is needed to assess benefits and risks.

Citation: Dhillon S. Tesamorelin: a review of its use in the management of HIV-associated lipodystrophy.. Drugs 2011.

BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2011 · PMID 22050344 · BioNex Evolve (PubMed-indexed)

This review examined human trials of tesamorelin in people with HIV-associated abdominal fat accumulation. Tesamorelin reduced fat around internal organs without a clinically significant effect on fat beneath the skin; internal abdominal fat returned after discontinuation. It was generally well tolerated, but the review states that longer-term experience is needed to assess benefits and risks.

Citation: Dhillon S. Spotlight on tesamorelin in HIV-associated lipodystrophy. BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy 2011.

AIDS (London, England) · 2011 · PMID 21516030 · BioNex Evolve (PubMed-indexed)

This randomized trial studied tesamorelin's effects on inflammation and blood-clot breakdown markers in people with HIV and excess abdominal fat. Tesamorelin reduced one clot-breakdown marker compared with placebo, and changes in several markers were associated with changes in fat around internal organs. The authors concluded that benefits may be modest and their clinical significance requires further study.

Citation: Stanley TL, Falutz J, Mamputu JC, Soulban G, Potvin D, Grinspoon SK. Effects of tesamorelin on inflammatory markers in HIV patients with excess abdominal fat: relationship with visceral adipose reduction. AIDS (London, England) 2011.

HIV/AIDS (Auckland, N.Z.) · 2011 · PMID 22096409 · BioNex Evolve (PubMed-indexed)

This review examined growth hormone and tesamorelin for body-fat changes in people with HIV receiving antiretroviral therapy. It reported that randomized human trials found tesamorelin safe and effective at reducing central fat accumulation. However, the effect was temporary, and whether it improves cardiovascular risk remained unclear.

Citation: Bedimo R. Growth hormone and tesamorelin in the management of HIV-associated lipodystrophy. HIV/AIDS (Auckland, N.Z.) 2011.

Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society · 2011 · PMID 21531600 · PubMed

This human study examined growth hormone release and adiponectin, a hormone produced by fat tissue, in men receiving tesamorelin. Total adiponectin was associated with certain measures of growth hormone release. However, short-term tesamorelin increased growth hormone and IGF-1 without significantly changing adiponectin, suggesting that body fat or other factors may explain the relationship.

Citation: Makimura H, Stanley TL, Chen CY, Branch KL, Grinspoon SK. Relationship of adiponectin to endogenous GH pulse secretion parameters in response to stimulation with a growth hormone releasing factor.. Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society 2011.

BETA : bulletin of experimental treatments for AIDS : a publication of the San Francisco AIDS Foundation · 2010 · PMID 21591600 · BioNex Evolve (PubMed-indexed)

The title indicates an update on tesamorelin but does not specify a study population or research question. The abstract was not available, so results are not summarized.

Citation: O'Neal R. Tesamorelin update.. BETA : bulletin of experimental treatments for AIDS : a publication of the San Francisco AIDS Foundation 2010.

Journal of acquired immune deficiency syndromes (1999) · 2010 · PMID 20101189 · BioNex Evolve (PubMed-indexed)

This randomized human trial studied tesamorelin in people with HIV and excess abdominal fat during antiretroviral therapy. Tesamorelin reduced fat around internal organs and improved distress about belly appearance, without significant side effects or changes in blood sugar measures. Fat reductions continued with ongoing treatment but were rapidly lost after switching to placebo.

Citation: Falutz J, Potvin D, Mamputu JC, Assaad H, Zoltowska M, Michaud SE, Berger D, Somero M, Moyle G, Brown S, Martorell C, Turner R, Grinspoon S. Effects of tesamorelin, a growth hormone-releasing factor, in HIV-infected patients with abdominal fat accumulation: a randomized placebo-controlled trial with a safety extension. Journal of acquired immune deficiency syndromes (1999) 2010.

Expert opinion on investigational drugs · 2009 · PMID 19243281 · BioNex Evolve (PubMed-indexed)

This review examined tesamorelin’s development and human studies, particularly for abnormal fat distribution associated with HIV. A randomized, placebo-controlled trial suggested that tesamorelin might be beneficial, reducing fat around internal organs with a good safety profile. Evidence for other potential uses appeared less promising.

Citation: Wang Y, Tomlinson B. Tesamorelin, a human growth hormone releasing factor analogue.. Expert opinion on investigational drugs 2009.

ClinicalTrials.gov · 2009 · NCT00795210 · ClinicalTrials.gov

This completed human trial compared short-term growth hormone treatment with growth hormone-releasing hormone in people with HIV, examining the body's own growth hormone release and blood sugar metabolism. The abstract describes predicted effects on hormone release and insulin sensitivity but reports no results.

Population / model

HIV Lipodystrophy

Citation: Massachusetts General Hospital. Effects of Short-term Growth Hormone in HIV-infected Patients. ClinicalTrials.gov 2009.

AIDS (London, England) · 2008 · PMID 18690162 · BioNex Evolve (PubMed-indexed)

This human trial extension studied longer-term tesamorelin use in people with HIV and abdominal fat accumulation. Continued treatment sustained reductions in fat around internal organs and triglycerides, was generally well tolerated, and did not worsen blood sugar control. The abdominal fat reaccumulated after tesamorelin was stopped.

Citation: Falutz J, Allas S, Mamputu JC, Potvin D, Kotler D, Somero M, Berger D, Brown S, Richmond G, Fessel J, Turner R, Grinspoon S. Long-term safety and effects of tesamorelin, a growth hormone-releasing factor analogue, in HIV patients with abdominal fat accumulation. AIDS (London, England) 2008.

New England Journal of Medicine · 2007 · editorial

This human study examined the metabolic effects of a growth hormone-releasing factor in patients with HIV. The abstract was not available, so results are not summarized.

Population / model

412 adults with HIV and abdominal fat accumulation

Limitations

Effects faded after stopping treatment; HIV population only.

Citation: Falutz J, et al.. Metabolic effects of a growth hormone-releasing factor in patients with HIV. New England Journal of Medicine 2007.

Basic & clinical pharmacology & toxicology · 2007 · PMID 17214611 · BioNex Evolve (PubMed-indexed)

This animal and laboratory study evaluated TH9507 using pigs, rats, dogs, and animal and human plasma. The modified peptide resisted breakdown and increased growth hormone and IGF-1 in animals. Reversible adverse effects were more evident in dogs and appeared associated with sustained, unusually high growth hormone and IGF-1 levels.

Citation: Ferdinandi ES, Brazeau P, High K, Procter B, Fennell S, Dubreuil P. Non-clinical pharmacology and safety evaluation of TH9507, a human growth hormone-releasing factor analogue. Basic & clinical pharmacology & toxicology 2007.

ClinicalTrials.gov · 2007 · NCT00608023 · ClinicalTrials.gov

This completed human extension trial assessed the effectiveness and long-term safety of TH9507, a growth hormone-releasing hormone analogue, in people with HIV and excess abdominal fat. The abstract provides no results.

Population / model

Lipodystrophy; HIV Infections

Citation: Theratechnologies. A Multicenter, Double-blind, Randomized, Placebo-controlled Extension Study Assessing the Efficacy and Long-term Safety of a 2 mg Dose of TH9507, a GHRH Analog, in HIV Subjects With Excess Abdominal Fat Accumulation. ClinicalTrials.gov 2007.

Current opinion in investigational drugs (London, England : 2000) · 2006 · PMID 17086939 · BioNex Evolve (PubMed-indexed)

This review described tesamorelin's development for several potential uses in humans, including HIV-related fat redistribution, sleep problems, recovery after hip fracture, and immune or cognitive effects. At the time of the review, human trials were underway, including studies of responses to influenza vaccination. The abstract reports no trial results.

Citation: Tomlinson B. Drug evaluation: tesamorelin, a synthetic human growth hormone releasing factor. Current opinion in investigational drugs (London, England : 2000) 2006.

ClinicalTrials.gov · 2006 · NCT00257712 · ClinicalTrials.gov

This completed human trial compared growth hormone-releasing hormone (GHRH) with placebo in healthy older adults and older adults with mild cognitive impairment. It examined memory and problem-solving ability, but the abstract reports no results.

Population / model

Aging; Mild Cognitive Impairment

Citation: University of Washington. GHRH: Cognition in Aging and MCI. ClinicalTrials.gov 2006.

ClinicalTrials.gov · 2005 · NCT00123253 · ClinicalTrials.gov

This completed human trial assessed TH9507's effectiveness and safety in people with HIV taking antiretroviral therapy who had excess abdominal fat. The abstract cites an earlier trial showing reduced fat around internal organs and in the trunk, without significant changes in limb fat or fat beneath the skin. It provides no results from the current trial.

Population / model

HIV Infections; Lipodystrophy

Citation: Theratechnologies. A Phase 3 Multicenter, Double-Blind, Randomized, Placebo-Controlled Study Assessing the Efficacy and Safety of a 2 mg Dose of TH9507, a Growth Hormone Releasing Factor Analog, in HIV Patients With Excess of Abdominal Fat Accumulation. ClinicalTrials.gov 2005.

International journal of pharmaceutics · 2004 · PMID 15113616 · BioNex Evolve (PubMed-indexed)

This animal study in dogs examined how TH9507, a growth hormone-releasing factor analogue, was absorbed after delivery into the lungs compared with injection. Lung delivery produced absorption into the bloodstream and a longer average time in the body than injection under the skin. The authors concluded that inhalation may provide a suitable alternative to injection under the skin.

Citation: Jansen M, Darby I, Abribat T, Dubreuil P, Ferdinandi ES, Hardy JG. Pulmonary delivery of TH9507, a growth hormone releasing factor analogue, in the dog. International journal of pharmaceutics 2004.

ClinicalTrials.gov · 2002 · NCT01264497 · ClinicalTrials.gov

This completed human trial studied TH9507, a modified form of growth hormone-releasing factor, in people with stable type 2 diabetes. It aimed to assess effects on the body’s response to insulin and diabetes control, but the abstract reports no results.

Population / model

Type 2 Diabetes

Citation: Theratechnologies. A Double-blind, Randomized, Parallel, Placebo-controlled 12-week Evaluation of the Safety of Two Doses of TH9507 in Subjects With Stable, Type 2 Diabetes Mellitus. ClinicalTrials.gov 2002.

BMC medicine · 2026 · PMID 41749205 · BioNex Evolve (PubMed-indexed)

This human trial tested thymalfasin with immunotherapy and chemotherapy before surgery for locally advanced stomach or gastroesophageal junction cancer. The combination produced encouraging tumor responses and clearance of cancer from lymph nodes, with safety described as acceptable despite some severe adverse events. Immune findings suggest thymalfasin may help coordinate antitumor immunity, but larger randomized trials are needed.

Citation: Xu H, Li F, Li B, Yang D, Liu T, Xia Y, Hua H, Li Q, Wang J, Liu H, Xu Z. Neoadjuvant immunochemotherapy plus thymalfasin in locally advanced gastric cancer: a prospective clinical trial. BMC medicine 2026.

ClinicalTrials.gov · 2026 · NCT07675980 · ClinicalTrials.gov

This recruiting randomized, double-blind, placebo-controlled human trial is evaluating thymosin alpha-1 in women with unexplained repeated embryo implantation failure undergoing fertility treatment. It is assessing safety and effectiveness as an added immune-modulating therapy. No results are reported.

Population / model

Recurrent Implantation Faliure

Citation: Fakih IVF Fertility Center. Thymosin-α1 for Recurrent Implantation Failure Following Transfer of PGT-a Tested Embryo: A Randomized, Double-Blind, Placebo-Controlled Trial. ClinicalTrials.gov 2026.

International journal of molecular sciences · 2025 · PMID 41373628 · BioNex Evolve (PubMed-indexed)

This review discusses thymosin alpha-1 and age-related immune decline, drawing on preclinical research and human clinical studies. It reports that thymosin alpha-1 can improve vaccine responses in older adults and reduce age-related deterioration in immune function. Longer-term effectiveness and safety in older adults still need validation.

Citation: Simonova MA, Ivanov I, Shoshina NS, Komyakova AM, Makarov DA, Baranovskii DS, Klabukov ID, Telepenina KP, Atiakshin DA, Shegay PV, Kaprin AD, Stepanenko VN. Aging and Thymosin Alpha-1.. International journal of molecular sciences 2025.

Frontiers in immunology · 2025 · PMID 40599771 · BioNex Evolve (PubMed-indexed)

This systematic review combined randomized human trials of thymosin alpha-1 in severe acute pancreatitis. It found improvements in some immune-cell measures and fewer infections outside the pancreas, but no significant reduction in lung infections or hospital stay. The authors concluded that thymosin alpha-1 may reduce inflammation and help prevent infections, with further research needed.

Citation: Tian Y, Yao J, Ma Y, Zhang P, Zhou X, Xie W, Tang W. Thymosin alpha 1 alleviates inflammation and prevents infection in patients with severe acute pancreatitis through immune regulation: a systematic review and meta-analysis. Frontiers in immunology 2025.

ClinicalTrials.gov · 2025 · NCT06829355 · ClinicalTrials.gov

This recruiting randomized human trial is testing whether adding thymalfasin to regorafenib and tislelizumab improves safety and effectiveness in advanced pMMR/MSS colorectal cancer after standard care has failed. It compares the combination with and without thymalfasin. No results are reported.

Population / model

MCRC

Citation: Beijing Friendship Hospital. Efficacy and Safety Study of Thymalfasin in Combination with Targeted Immunotherapy (Regorafenib and Tislelizumab) in Patients with Advanced PMMR/MSS Colorectal Cancer Who Failed Standard of Care: a Multicenter, Open-label, Randomized, Controlled Clinical Study. ClinicalTrials.gov 2025.

Journal of the College of Physicians and Surgeons--Pakistan : JCPSP · 2024 · PMID 39648386 · BioNex Evolve (PubMed-indexed)

This systematic review combined randomized human trials of thymosin alpha-1 added to routine care during acute worsening of chronic obstructive pulmonary disease. Compared with routine care alone, it improved lung function, blood oxygen and carbon dioxide measures, and immune-cell measures, and shortened hospital stays. The authors called for higher-quality trials to confirm effectiveness.

Citation: Cao A, Feng F, Zhou X. Thymosin Alpha 1 Plus Routine Treatment for the Acute Exacerbation of Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis. Journal of the College of Physicians and Surgeons--Pakistan : JCPSP 2024.

Alternative therapies in health and medicine · 2024 · PMID 38308608 · BioNex Evolve (PubMed-indexed)

This narrative review examined human clinical studies of thymosin alpha-1 for COVID-19, other infections, autoimmune conditions, and cancer. The authors reported consistent evidence of safety and effectiveness across the conditions reviewed and concluded that thymosin alpha-1 was a well-tolerated, effective regulator of immune responses.

Citation: Dinetz E, Lee E. Comprehensive Review of the Safety and Efficacy of Thymosin Alpha 1 in Human Clinical Trials. Alternative therapies in health and medicine 2024.

Biotechnology & genetic engineering reviews · 2024 · PMID 37248723 · BioNex Evolve (PubMed-indexed)

This randomized human study compared chemotherapy with or without thymalfasin in people undergoing colorectal cancer surgery. The thymalfasin groups had fewer infections and postoperative complications, better immune-function measures, lower local recurrence and distant spread, and longer survival without disease. These findings were reported in comparison with chemotherapy alone.

Citation: Niu W, Li Z, Li Z, Hu X, Wang X, Ding Y, Li C, Yu B. A Prospective and Randomized Control Study on Effects of Thymalfasin for Injection on Perioperative Immune Function and Long-term Prognosis of Patients with Colorectal Cancer. Biotechnology & genetic engineering reviews 2024.

Frontiers in medicine · 2024 · PMID 38903817 · BioNex Evolve (PubMed-indexed)

This review discusses thymosin alpha-1 research in preclinical settings and humans as an example of discovering drugs by observing their effects rather than starting with a known molecular target. It explores how this approach could fit precision medicine. The abstract does not report specific efficacy or safety findings.

Citation: Garaci E, Paci M, Matteucci C, Costantini C, Puccetti P, Romani L. Phenotypic drug discovery: a case for thymosin alpha-1. Frontiers in medicine 2024.

Medicine · 2024 · PMID 39183403 · BioNex Evolve (PubMed-indexed)

This case report described a woman with previously treated metastatic triple-negative breast cancer who received radiation, immunotherapy, an immune-cell growth factor, and thymosin alpha-1. The combined regimen produced a partial tumor response, including shrinkage outside the irradiated area. A skin reaction improved with treatment; the report does not establish thymosin alpha-1's separate contribution.

Citation: Yu J, Wang Q, Wang L, Zong D, He X. PD-1 inhibitor combined with SBRT, GM-CSF, and thymosin alpha-1 in metastatic breast cancer: A case report and literature review. Medicine 2024.

ClinicalTrials.gov · 2024 · NCT06598839 · ClinicalTrials.gov

This human trial examines thymosin alpha 1 after surgery for stage I non-small cell lung cancer, focusing on tumor cells circulating in the blood and age-related decline in immune function. It is recruiting participants, and no results are reported.

Population / model

Non Small Cell Lung Cancer

Citation: Yousheng Mao. Assessment of the Efficacy of Immunomodulatory Therapy With Thymosin Alpha 1 (Tα1) Following Surgical Resection in Patients With Stage I Non-Small Cell Lung Cancer. ClinicalTrials.gov 2024.

ClinicalTrials.gov · 2024 · NCT06552598 · ClinicalTrials.gov

This human trial studies the safety, tolerability, and early effectiveness of KD01, an engineered cancer-killing virus, in people with gynecologic cancers, including cervical and endometrial cancer. It also plans to examine immune effects and how KD01 kills tumor cells. The trial is recruiting, and no results are reported.

Population / model

Cervical Cancer; Gynecologic Malignancies; Endometrial Cancer

Citation: Tongji Hospital. Phase I/II Clinical Study to Evaluate the Safety, Tolerability, and Preliminary Efficacy of Local Administration of Recombinant Oncolytic Adenovirus Injection (KD01) in Patients With Gynecologic Malignancies. ClinicalTrials.gov 2024.

ClinicalTrials.gov · 2024 · NCT06607926 · ClinicalTrials.gov

This registered human trial plans to assess the safety and effectiveness of thymosin alpha-1 combined with chemotherapy and PD-1 immune checkpoint inhibitors before surgery in people with operable non-small cell lung cancer. It has not yet begun recruiting, and no results are reported.

Population / model

Resectable Non-Small-Cell Lung Cancer

Citation: Xuanwu Hospital, Beijing. Efficacy and Safety of Thymosin α1 Plus Immune Checkpoint Inhibitors and Chemotherapy as Neoadjuvant Therapy in Patients With Resectable Stage II - IIIB Non Small Cell Lung Cancer: A Prospective, Multicenter, Randomized, Controlled Trial. ClinicalTrials.gov 2024.

The Journal of infectious diseases · 2023 · PMID 36056913 · BioNex Evolve (PubMed-indexed)

This open-label randomized pilot trial compared thymalfasin with standard care in hospitalized COVID-19 patients with low blood oxygen and low lymphocyte counts. Clinical recovery was more frequent with thymalfasin, but the differences were not statistically significant. Among patients receiving low-flow oxygen, CD4+ immune-cell counts increased faster; serious adverse events in treated patients were judged unrelated to thymalfasin.

Citation: Shehadeh F, Benitez G, Mylona EK, Tran QL, Tsikala-Vafea M, Atalla E, Kaczynski M, Mylonakis E. A Pilot Trial of Thymalfasin (Thymosin-α-1) to Treat Hospitalized Patients With Hypoxemia and Lymphocytopenia Due to Coronavirus Disease 2019 Infection.. The Journal of infectious diseases 2023.

International immunopharmacology · 2023 · PMID 36881981 · BioNex Evolve (PubMed-indexed)

This preliminary randomized human trial report examined thymalfasin for preventing COVID-19 and reducing its severity in people receiving hemodialysis. Fewer deaths and COVID-19-related serious adverse events had been reported in the thymalfasin group than in controls, but these were preliminary observations. The study was nearing completion, with final safety, effectiveness, and antibody analyses still pending.

Citation: Tuthill CW, Awad A, Parrigon M, Ershler WB. A pilot trial of Thymalfasin (Ta1) to prevent covid-19 infection and morbidities in renal dialysis patients: Preliminary report. International immunopharmacology 2023.

Inflammopharmacology · 2023 · PMID 37845598 · BioNex Evolve (PubMed-indexed)

This systematic review combined studies of thymosin alpha-1 in people with moderate to critical COVID-19. Its use was associated with lower mortality, but there was no significant difference in the need for mechanical ventilation or length of hospital stay compared with placebo. The authors concluded that it may reduce mortality, but randomized trials are needed to verify the findings.

Citation: Soeroto AY, Suryadinata H, Yanto TA, Hariyanto TI. The efficacy of thymosin alpha-1 therapy in moderate to critical COVID-19 patients: a systematic review, meta-analysis, and meta-regression. Inflammopharmacology 2023.

ClinicalTrials.gov · 2023 · NCT06139419 · ClinicalTrials.gov

This randomized human trial evaluated thymosin alpha-1 in patients with locally advanced non-small cell lung cancer receiving chemoradiotherapy followed by immunotherapy. It aimed to assess survival, treatment responses, and toxic effects. The trial is listed as completed, but the abstract reports no results.

Population / model

Non-small Cell Lung Cancer

Citation: Sun Yat-sen University. A Prospective Phase II Controlled Study to Evaluate the Impact of Thymosin Alpha 1 on the Completion Rate of Consolidation Immunotherapy After Radical Radiochemotherapy for Locally Advanced Non-Small Cell Lung Cancer. ClinicalTrials.gov 2023.

ClinicalTrials.gov · 2023 · NCT07644897 · ClinicalTrials.gov

This recruiting human trial is evaluating thymosin alpha-1 combined with the anti-PD-1 antibody toripalimab in older adults with advanced melanoma. It will assess effectiveness, safety, and tolerability without a comparison group; no results are reported.

Population / model

Melanoma; Immune-related Adverse Event; Immune Checkpoint Inhibitor

Citation: Sun Yat-sen University. Thymosin Alpha 1 Combined With Anti-PD-1 Monoclonal Antibody in Elderly Patients With Advanced Melanoma. ClinicalTrials.gov 2023.

ClinicalTrials.gov · 2023 · NCT06178146 · ClinicalTrials.gov

This registered randomized human trial investigates the effectiveness and safety of thymosin alpha-1 for moderate to severe immune-related adverse events. Its status is unknown, and the abstract reports no results from this trial.

Population / model

IrAE

Citation: Jun Wang. A Prospective, Open, Randomized Controlled Stage II Trial Investigating the Efficacy and Safety of Thymosin Alpha-1 in Treating Moderate to Severe Immune-related Adverse Events. ClinicalTrials.gov 2023.

ClinicalTrials.gov · 2023 · NCT05790447 · ClinicalTrials.gov

This registered human trial studies a thymalfasin-based combination with radiotherapy, PD-1/PD-L1 immunotherapy, and the immune-stimulating protein GM-CSF in patients with advanced solid tumors resistant to treatment. It has no comparison group. Its status is unknown, and the abstract reports no results.

Population / model

Advanced Solid Tumor; Refractory Tumor

Citation: Second Affiliated Hospital of Soochow University. Treatment of Advanced Refractory Solid Tumors Based on Precise Thymalfasin-regulated PRaG Mode: an Open-label, Prospective, Multicenter Study (PRaG 5.0 Study). ClinicalTrials.gov 2023.

International immunopharmacology · 2022 · PMID 35994852 · BioNex Evolve (PubMed-indexed)

This animal study tested thymosin alpha-1 added to heated abdominal chemotherapy in mice with colon cancer spread within the abdomen. The combination increased survival compared with chemotherapy alone and sham treatment. Thymosin alpha-1 promoted an antitumor immune response and immune-cell entry into tumors, but did not directly inhibit tumor-cell growth.

Citation: Nevo N, Lee Goldstein A, Bar-David S, Natanson M, Alon G, Lahat G, Nizri E. Thymosin alpha 1 as an adjuvant to hyperthermic intraperitoneal chemotherapy in an experimental model of peritoneal metastases from colonic carcinoma. International immunopharmacology 2022.