{"@context":"https://schema.org","@type":"Dataset","name":"LYO Research evidence grades for peptides","description":"Evidence-graded outcomes for peptides, human studies only, with references. Grades: A established, B probable, C weak, D no human evidence.","url":"https://lyoresearch.com/api/v1/compounds","license":"https://creativecommons.org/licenses/by/4.0/","creator":{"@type":"Organization","name":"LYO Research","url":"https://lyoresearch.com"},"dateModified":"2026-09-02","version":"2026-09-02","count":8,"compounds":[{"id":"bpc-157","name":"BPC-157","aliases":["Body Protection Compound 157","BPC157","Bepecin"],"url":"https://lyoresearch.com/compounds/bpc-157","summary":"BPC-157 is a synthetic 15-amino-acid peptide derived from a protein found in human gastric juice. In rodents it consistently speeds healing of tendon, ligament, muscle and gut injury. In people it has never been tested in a controlled trial, so every human claim about it — healing, pain relief, safety — is currently unproven. It is not an approved medicine anywhere and is prohibited in sport.","overall_grade":"D","overall_grade_meaning":"no human evidence","human_trials":"0 controlled","regulatory_status":"Not approved","outcomes":[{"outcome":"Tendon & ligament healing","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"0 controlled","evidence":"Rodent models of Achilles and MCL injury. Consistent in animals; no human trial has been run.","references":[{"citation":"Sikiric P, et al. Stable gastric pentadecapeptide BPC 157: novel therapy in gastrointestinal tract.","where":"Curr Pharm Des, 2011 (review)","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Sikiric+BPC+157+gastrointestinal+review+2011"},{"citation":"Chang CH, et al. The promoting effect of pentadecapeptide BPC 157 on tendon healing involves tendon outgrowth, cell survival, and cell migration.","where":"J Appl Physiol, 2011","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Chang+BPC+157+tendon+healing+2011"}]},{"outcome":"Gut mucosal healing","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"0 controlled","evidence":"Rat ulcer and colitis models. The original research programme; still preclinical.","references":[{"citation":"Sikiric P, et al. Stable gastric pentadecapeptide BPC 157: novel therapy in gastrointestinal tract.","where":"Curr Pharm Des, 2011 (review)","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Sikiric+BPC+157+gastrointestinal+review+2011"}]},{"outcome":"Pain reduction","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"1 case series (n=12)","evidence":"A retrospective case report of 12 knee-pain patients given intra-articular injections; no control group. The only human study a 2025 systematic review could find.","references":[{"citation":"Vasireddi N, Hahamyan H, Salata MJ, et al. Emerging use of BPC-157 in orthopaedic sports medicine: a systematic review.","where":"HSS Journal, 2025;21(4):485–495","url":"https://doi.org/10.1177/15563316251355551"}]},{"outcome":"Safety in humans","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":true,"human_studies":"1 open-label pilot (n=2)","evidence":"Two healthy adults given intravenous doses in an uncontrolled 2025 pilot showed no biomarker changes. That is the entire human safety literature.","references":[{"citation":"Vasireddi N, Hahamyan H, Salata MJ, et al. Emerging use of BPC-157 in orthopaedic sports medicine: a systematic review.","where":"HSS Journal, 2025;21(4):485–495","url":"https://doi.org/10.1177/15563316251355551"},{"citation":"Lee E, Burgess J. Intravenous BPC-157 in healthy adults: an open-label pilot.","where":"2025 (pilot, n = 2)","url":"https://pubmed.ncbi.nlm.nih.gov/?term=BPC+157+intravenous+pilot+healthy+adults+2025"},{"citation":"U.S. FDA. Certain bulk drug substances for use in compounding that may present significant safety risks (BPC-157).","where":"FDA, 2023","url":"https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks"}]}],"regions":[{"region":"European Union","status":"Unapproved medicinal product","note":"No marketing authorisation. Sale for human use is an offence for the seller."},{"region":"United States","status":"Not approved; compounding restricted","note":"FDA placed BPC-157 in a category that bars it from pharmacy compounding, citing safety uncertainty."},{"region":"Sport (WADA)","status":"Prohibited","note":"Listed as a non-approved substance under the prohibited list since 2022."},{"region":"Sweden","status":"Unapproved","note":"Läkemedelsverket treats it as a medicine without authorisation."}],"faq":[{"q":"Is there any human research on BPC-157?","a":"No controlled trials. A 2025 systematic review screened 544 articles from 1993–2024 and found one human study — a retrospective case report of 12 patients — alongside 35 animal studies. A separate 2025 pilot gave the peptide intravenously to two healthy volunteers without a control group. Neither design can show that the peptide caused an effect."},{"q":"Why is the grade D if the animal results are so consistent?","a":"Because LYO grades only count human evidence. Consistent animal data is exactly the reason a human trial should be run — it is not a reason to grade as though one had been."},{"q":"Is BPC-157 safe?","a":"Unknown. No systematic safety data exists in humans. A lack of reported harm in a market with no reporting system is not evidence of safety."},{"q":"Is BPC-157 legal?","a":"It is not an approved medicine in any major market. In the EU, selling it for human use is an offence for the seller. It is prohibited in sport by WADA. Rules for possession vary by country."}],"references":[{"cite":"Sikiric P, et al. Stable gastric pentadecapeptide BPC 157: novel therapy in gastrointestinal tract.","where":"Curr Pharm Des, 2011 (review)","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Sikiric+BPC+157+gastrointestinal+review+2011","note":"Animal data; the originating laboratory."},{"cite":"Chang CH, et al. The promoting effect of pentadecapeptide BPC 157 on tendon healing involves tendon outgrowth, cell survival, and cell migration.","where":"J Appl Physiol, 2011","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Chang+BPC+157+tendon+healing+2011","note":"Rat Achilles tendon model."},{"cite":"Vasireddi N, Hahamyan H, Salata MJ, et al. Emerging use of BPC-157 in orthopaedic sports medicine: a systematic review.","where":"HSS Journal, 2025;21(4):485–495","url":"https://doi.org/10.1177/15563316251355551","note":"544 articles screened; 36 included — 35 preclinical, 1 clinical (a 12-patient retrospective case report). No clinical safety data found."},{"cite":"Lee E, Burgess J. Intravenous BPC-157 in healthy adults: an open-label pilot.","where":"2025 (pilot, n = 2)","url":"https://pubmed.ncbi.nlm.nih.gov/?term=BPC+157+intravenous+pilot+healthy+adults+2025","note":"Uncontrolled; biomarkers only; no efficacy endpoints. Same research group as other human reports."},{"cite":"U.S. FDA. Certain bulk drug substances for use in compounding that may present significant safety risks (BPC-157).","where":"FDA, 2023","url":"https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks","note":"Regulatory status in the United States."}],"last_reviewed":"2026-09-02","literature_searched_to":"2026-09-02","changelog":[{"date":"2026-09-02","note":"Human-evidence rows made precise: one retrospective case series (n=12) and one open-label IV pilot (n=2) now cited; 2025 systematic review added. Grades unchanged."},{"date":"2026-09-01","note":"Initial publication. All outcomes graded D on the basis of no controlled human trials."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"semaglutide","name":"Semaglutide","aliases":["Ozempic","Wegovy","Rybelsus","GLP-1 receptor agonist"],"url":"https://lyoresearch.com/compounds/semaglutide","summary":"Semaglutide is a once-weekly GLP-1 receptor agonist approved for type 2 diabetes and, at a higher dose, for weight management. In large randomised trials it produces roughly 15% average weight loss over 68 weeks and reduces major cardiovascular events in people with existing heart disease. Gastrointestinal side effects are common and are the main reason people stop. It is a prescription medicine; products sold outside that channel are unlicensed copies.","overall_grade":"A","overall_grade_meaning":"established in humans","human_trials":"30+ RCTs","regulatory_status":"Approved (Rx)","outcomes":[{"outcome":"Body weight","grade":"A","grade_meaning":"established in humans","effect_size":"large","adverse":false,"human_studies":"15+ RCTs","evidence":"STEP programme. Roughly 15% mean loss at 68 weeks versus placebo; consistent across trials.","references":[{"citation":"Wilding JPH, et al. Once-weekly semaglutide in adults with overweight or obesity (STEP 1).","where":"N Engl J Med, 2021;384:989–1002","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Wilding+STEP+1+semaglutide+2021+NEJM"}]},{"outcome":"Blood glucose (HbA1c)","grade":"A","grade_meaning":"established in humans","effect_size":"large","adverse":false,"human_studies":"10+ RCTs","evidence":"SUSTAIN programme; the original approval basis in type 2 diabetes.","references":[{"citation":"Sorli C, et al. Efficacy and safety of once-weekly semaglutide monotherapy versus placebo in type 2 diabetes (SUSTAIN 1).","where":"Lancet Diabetes Endocrinol, 2017","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Sorli+SUSTAIN+1+semaglutide+2017"}]},{"outcome":"Major cardiovascular events","grade":"A","grade_meaning":"established in humans","effect_size":"moderate","adverse":false,"human_studies":"1 large RCT","evidence":"SELECT trial, 17,604 participants: a 20% relative reduction in people with established cardiovascular disease and no diabetes.","references":[{"citation":"Lincoff AM, et al. Semaglutide and cardiovascular outcomes in obesity without diabetes (SELECT).","where":"N Engl J Med, 2023;389:2221–2232","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Lincoff+SELECT+semaglutide+cardiovascular+2023"}]},{"outcome":"GI side effects","grade":"A","grade_meaning":"established in humans","effect_size":"large","adverse":true,"human_studies":"All trials","evidence":"Nausea, vomiting and constipation are the most common reasons people stop. Well quantified.","references":[{"citation":"Wilding JPH, et al. Once-weekly semaglutide in adults with overweight or obesity (STEP 1).","where":"N Engl J Med, 2021;384:989–1002","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Wilding+STEP+1+semaglutide+2021+NEJM"},{"citation":"Lincoff AM, et al. Semaglutide and cardiovascular outcomes in obesity without diabetes (SELECT).","where":"N Engl J Med, 2023;389:2221–2232","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Lincoff+SELECT+semaglutide+cardiovascular+2023"}]},{"outcome":"Lean mass loss","grade":"B","grade_meaning":"probable, not settled","effect_size":"moderate","adverse":true,"human_studies":"Sub-studies","evidence":"A share of weight lost is lean tissue; magnitude and clinical importance still debated.","references":[{"citation":"Wilding JPH, et al. Once-weekly semaglutide in adults with overweight or obesity (STEP 1).","where":"N Engl J Med, 2021;384:989–1002","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Wilding+STEP+1+semaglutide+2021+NEJM"},{"citation":"Wilding JPH, et al. Weight regain and cardiometabolic effects after withdrawal of semaglutide: the STEP 1 trial extension.","where":"Diabetes Obes Metab, 2022","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Wilding+STEP+1+extension+withdrawal+semaglutide+2022"}]}],"regions":[{"region":"European Union","status":"Approved, prescription-only","note":"Authorised by the EMA. Grey-market versions are unlicensed medicines."},{"region":"United States","status":"Approved, prescription-only","note":"FDA-approved. Compounded versions were permitted during shortage and are now restricted."},{"region":"United Kingdom","status":"Approved, prescription-only","note":"MHRA has issued warnings about counterfeit pens."},{"region":"Sweden","status":"Approved, prescription-only","note":"Subsidy rules for weight management differ from diabetes."}],"faq":[{"q":"How much weight do people lose on semaglutide?","a":"In the STEP 1 trial, adults without diabetes lost about 15% of body weight on average over 68 weeks, compared with about 2.4% on placebo. Individual results vary widely."},{"q":"Does the weight come back after stopping?","a":"Largely, yes. In the trial that withdrew treatment after a year, participants regained about two-thirds of the lost weight within the following year."},{"q":"Is semaglutide a peptide?","a":"Yes — it is a 31-amino-acid peptide, a modified form of the natural hormone GLP-1."},{"q":"Why are there so many fake versions?","a":"Demand outstripped supply for several years, and the molecule is relatively simple to synthesise. Products sold outside the prescription channel are unlicensed and, in enforcement seizures, frequently underdosed or misidentified."}],"references":[{"cite":"Wilding JPH, et al. Once-weekly semaglutide in adults with overweight or obesity (STEP 1).","where":"N Engl J Med, 2021;384:989–1002","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Wilding+STEP+1+semaglutide+2021+NEJM","note":"1,961 adults; −14.9% vs −2.4% at 68 weeks."},{"cite":"Sorli C, et al. Efficacy and safety of once-weekly semaglutide monotherapy versus placebo in type 2 diabetes (SUSTAIN 1).","where":"Lancet Diabetes Endocrinol, 2017","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Sorli+SUSTAIN+1+semaglutide+2017","note":"First of the SUSTAIN programme."},{"cite":"Lincoff AM, et al. Semaglutide and cardiovascular outcomes in obesity without diabetes (SELECT).","where":"N Engl J Med, 2023;389:2221–2232","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Lincoff+SELECT+semaglutide+cardiovascular+2023","note":"17,604 participants; hazard ratio 0.80 for MACE."},{"cite":"Wilding JPH, et al. Weight regain and cardiometabolic effects after withdrawal of semaglutide: the STEP 1 trial extension.","where":"Diabetes Obes Metab, 2022","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Wilding+STEP+1+extension+withdrawal+semaglutide+2022","note":"Two-thirds of lost weight regained within a year of stopping."}],"last_reviewed":"2026-09-01","literature_searched_to":"2026-09-01","changelog":[{"date":"2026-09-01","note":"Initial publication."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"retatrutide","name":"Retatrutide","aliases":["LY3437943","triple agonist","GIP/GLP-1/glucagon agonist"],"url":"https://lyoresearch.com/compounds/retatrutide","summary":"Retatrutide is an investigational once-weekly peptide that activates three receptors at once: GIP, GLP-1 and glucagon. Phase 3 topline results announced in December 2025 and May 2026 report average weight loss of about 26–29% at 68–80 weeks — the largest yet for a single drug — with high rates of nausea and more people stopping for side effects than on placebo. The full data are not yet peer-reviewed. It is not approved anywhere, and no legitimate supply exists outside clinical trials.","overall_grade":"B","overall_grade_meaning":"probable, not settled","human_trials":"Phase 3 topline","regulatory_status":"Investigational","outcomes":[{"outcome":"Body weight","grade":"B","grade_meaning":"probable, not settled","effect_size":"large","adverse":false,"human_studies":"1 phase 2 RCT published; 2 phase 3 RCTs topline","evidence":"Phase 2: −24.2% at 48 weeks on 12 mg. Phase 3 TRIUMPH-4: −28.7% at 68 weeks vs −2.1% placebo. TRIUMPH-1 (2,339 adults): −28.3% at 80 weeks on 12 mg, −30.3% at 104 weeks in the BMI ≥35 extension. Press releases; peer review pending.","references":[{"citation":"Jastreboff AM, et al. Triple-hormone-receptor agonist retatrutide for obesity — a phase 2 trial.","where":"N Engl J Med, 2023;389:514–526","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Jastreboff+retatrutide+phase+2+obesity+2023"},{"citation":"Eli Lilly. Retatrutide delivered weight loss of up to an average of 71.2 lbs along with substantial relief from osteoarthritis pain in first successful phase 3 trial (TRIUMPH-4).","where":"Press release, 11 Dec 2025","url":"https://investor.lilly.com/news-releases/news-release-details/lillys-triple-agonist-retatrutide-delivered-weight-loss-average"},{"citation":"Eli Lilly. Retatrutide TRIUMPH-1 topline results (NCT05929066).","where":"Press release, May 2026","url":"https://www.ajmc.com/view/retatrutide-achieves-up-to-30-3-average-weight-loss-in-phase-3-triumph-1-trial"}]},{"outcome":"Knee osteoarthritis pain","grade":"B","grade_meaning":"probable, not settled","effect_size":"moderate","adverse":false,"human_studies":"1 phase 3 RCT topline","evidence":"TRIUMPH-4 enrolled adults with obesity and knee osteoarthritis: WOMAC pain fell by up to 4.5 points (75.8%) vs 2.4 (40.3%) on placebo. Weight loss likely explains much of it; not yet peer-reviewed.","references":[{"citation":"Eli Lilly. Retatrutide delivered weight loss of up to an average of 71.2 lbs along with substantial relief from osteoarthritis pain in first successful phase 3 trial (TRIUMPH-4).","where":"Press release, 11 Dec 2025","url":"https://investor.lilly.com/news-releases/news-release-details/lillys-triple-agonist-retatrutide-delivered-weight-loss-average"}]},{"outcome":"GI side effects","grade":"B","grade_meaning":"probable, not settled","effect_size":"large","adverse":true,"human_studies":"Phase 2 + phase 3 topline","evidence":"TRIUMPH-4: nausea 38–43% vs 11%, vomiting 20–21% vs 0%; discontinuation for adverse events 12–18% vs 4%. TRIUMPH-1: 11.3% stopped on 12 mg vs 4.9% placebo.","references":[{"citation":"Jastreboff AM, et al. Triple-hormone-receptor agonist retatrutide for obesity — a phase 2 trial.","where":"N Engl J Med, 2023;389:514–526","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Jastreboff+retatrutide+phase+2+obesity+2023"},{"citation":"Eli Lilly. Retatrutide delivered weight loss of up to an average of 71.2 lbs along with substantial relief from osteoarthritis pain in first successful phase 3 trial (TRIUMPH-4).","where":"Press release, 11 Dec 2025","url":"https://investor.lilly.com/news-releases/news-release-details/lillys-triple-agonist-retatrutide-delivered-weight-loss-average"},{"citation":"Eli Lilly. Retatrutide TRIUMPH-1 topline results (NCT05929066).","where":"Press release, May 2026","url":"https://www.ajmc.com/view/retatrutide-achieves-up-to-30-3-average-weight-loss-in-phase-3-triumph-1-trial"}]},{"outcome":"Dysesthesia (skin sensation changes)","grade":"B","grade_meaning":"probable, not settled","effect_size":"small","adverse":true,"human_studies":"Phase 3 topline","evidence":"Reported in 9–21% of treated participants vs 0.7% on placebo in TRIUMPH-4 — an effect not prominent with older GLP-1 drugs.","references":[{"citation":"Eli Lilly. Retatrutide delivered weight loss of up to an average of 71.2 lbs along with substantial relief from osteoarthritis pain in first successful phase 3 trial (TRIUMPH-4).","where":"Press release, 11 Dec 2025","url":"https://investor.lilly.com/news-releases/news-release-details/lillys-triple-agonist-retatrutide-delivered-weight-loss-average"}]}],"regions":[{"region":"European Union","status":"Not authorised — investigational","note":"No marketing application decided. Any product sold as retatrutide in the EU is an unlicensed medicine of unknown provenance."},{"region":"United States","status":"Not approved — in phase 3","note":"Available only inside clinical trials. Lilly has said it expects to file for approval after the TRIUMPH programme completes."},{"region":"United Kingdom","status":"Not authorised","note":"MHRA has warned about unlicensed weight-loss injectables sold online."},{"region":"Sweden","status":"Not authorised","note":"Not on the Läkemedelsverket register; cannot be prescribed."}],"faq":[{"q":"How much weight do people lose on retatrutide?","a":"In the phase 3 TRIUMPH-1 topline, adults on the 12 mg dose lost 28.3% of body weight on average over 80 weeks, and 30.3% at 104 weeks in a heavier subgroup. In phase 2 the figure was 24.2% at 48 weeks. These are averages from press releases; the peer-reviewed papers will give the spread."},{"q":"Is retatrutide better than tirzepatide?","a":"Probably more weight loss, on the numbers so far — but no trial has compared them head-to-head, and cross-trial comparisons are unreliable. The side-effect burden also appears higher. Treat “better” as unsettled until a direct comparison exists."},{"q":"Is retatrutide available?","a":"Not legally, anywhere. It is an investigational medicine available only in clinical trials. Products sold online under the name are unlicensed and, in enforcement seizures, frequently not what the label says."},{"q":"Why is the grade B and not A?","a":"Because the phase 3 results exist only as company press releases. LYO's A grade requires peer-reviewed publication of multiple trials. The grade will be reviewed when the TRIUMPH papers appear."}],"references":[{"cite":"Jastreboff AM, et al. Triple-hormone-receptor agonist retatrutide for obesity — a phase 2 trial.","where":"N Engl J Med, 2023;389:514–526","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Jastreboff+retatrutide+phase+2+obesity+2023","note":"338 adults; −24.2% at 48 weeks on 12 mg."},{"cite":"Eli Lilly. Retatrutide delivered weight loss of up to an average of 71.2 lbs along with substantial relief from osteoarthritis pain in first successful phase 3 trial (TRIUMPH-4).","where":"Press release, 11 Dec 2025","url":"https://investor.lilly.com/news-releases/news-release-details/lillys-triple-agonist-retatrutide-delivered-weight-loss-average","note":"445 adults, 68 weeks. Topline; not peer-reviewed."},{"cite":"Eli Lilly. Retatrutide TRIUMPH-1 topline results (NCT05929066).","where":"Press release, May 2026","url":"https://www.ajmc.com/view/retatrutide-achieves-up-to-30-3-average-weight-loss-in-phase-3-triumph-1-trial","note":"2,339 adults, 80 weeks plus 104-week extension. Detailed data promised for the ADA Scientific Sessions; not peer-reviewed at time of review."}],"last_reviewed":"2026-09-02","literature_searched_to":"2026-09-02","changelog":[{"date":"2026-09-02","note":"Full page: mechanism, regulatory status and FAQ added. Phase 3 topline results (TRIUMPH-4, TRIUMPH-1) with osteoarthritis-pain and dysesthesia rows. Grade held at B pending peer-reviewed publication."},{"date":"2026-09-01","note":"Initial publication."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"tirzepatide","name":"Tirzepatide","aliases":["Mounjaro","Zepbound","dual GIP/GLP-1 agonist"],"url":"https://lyoresearch.com/compounds/tirzepatide","summary":"Tirzepatide is a once-weekly peptide that activates both GIP and GLP-1 receptors. It is approved for type 2 diabetes, weight management and obstructive sleep apnoea, and in the only direct head-to-head trial it produced more weight loss than semaglutide (20.2% vs 13.7% at 72 weeks) with a similar side-effect profile. It is a prescription medicine; versions sold outside that channel are unlicensed.","overall_grade":"A","overall_grade_meaning":"established in humans","human_trials":"15+ RCTs","regulatory_status":"Approved (Rx)","outcomes":[{"outcome":"Body weight","grade":"A","grade_meaning":"established in humans","effect_size":"large","adverse":false,"human_studies":"10+ RCTs","evidence":"SURMOUNT-1: −20.9% at 72 weeks on 15 mg vs −3.1% placebo in 2,539 adults. SURMOUNT-5 head-to-head: −20.2% vs −13.7% on semaglutide at 72 weeks.","references":[{"citation":"Jastreboff AM, et al. Tirzepatide once weekly for the treatment of obesity (SURMOUNT-1).","where":"N Engl J Med, 2022;387:205–216","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Jastreboff+SURMOUNT-1+tirzepatide+2022"},{"citation":"Aronne LJ, Horn DB, le Roux CW, et al. Tirzepatide as compared with semaglutide for the treatment of obesity (SURMOUNT-5).","where":"N Engl J Med, 2025;393(1):26–36","url":"https://pubmed.ncbi.nlm.nih.gov/40353578/"}]},{"outcome":"Blood glucose (HbA1c)","grade":"A","grade_meaning":"established in humans","effect_size":"large","adverse":false,"human_studies":"5 SURPASS RCTs","evidence":"SURPASS-2: HbA1c reductions of 2.0–2.3 points vs 1.9 on semaglutide 1 mg in type 2 diabetes.","references":[{"citation":"Frías JP, et al. Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes (SURPASS-2).","where":"N Engl J Med, 2021;385:503–515","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Frias+SURPASS-2+tirzepatide+semaglutide+2021"}]},{"outcome":"Obstructive sleep apnoea","grade":"A","grade_meaning":"established in humans","effect_size":"moderate","adverse":false,"human_studies":"2 RCTs","evidence":"SURMOUNT-OSA: apnoea–hypopnoea index fell by roughly 25–30 events per hour vs 5–6 on placebo; basis of the 2024 approval.","references":[{"citation":"Malhotra A, et al. Tirzepatide for the treatment of obstructive sleep apnea and obesity (SURMOUNT-OSA).","where":"N Engl J Med, 2024;391:1193–1205","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Malhotra+SURMOUNT-OSA+tirzepatide+2024"}]},{"outcome":"Cardiovascular events","grade":"B","grade_meaning":"probable, not settled","effect_size":"small","adverse":false,"human_studies":"1 outcomes RCT (2025)","evidence":"SURPASS-CVOT reported tirzepatide non-inferior to dulaglutide on major adverse cardiovascular events in type 2 diabetes; superiority over an active GLP-1 comparator was not shown.","references":[{"citation":"Eli Lilly. SURPASS-CVOT topline: tirzepatide vs dulaglutide on cardiovascular outcomes in type 2 diabetes.","where":"Press release, 2025; full publication pending at time of review","url":"https://pubmed.ncbi.nlm.nih.gov/?term=SURPASS-CVOT+tirzepatide+dulaglutide"}]},{"outcome":"GI side effects","grade":"A","grade_meaning":"established in humans","effect_size":"large","adverse":true,"human_studies":"All trials","evidence":"Nausea, diarrhoea and vomiting, mostly during dose escalation. In SURMOUNT-5, GI-related discontinuation was 2.7% vs 5.6% on semaglutide.","references":[{"citation":"Jastreboff AM, et al. Tirzepatide once weekly for the treatment of obesity (SURMOUNT-1).","where":"N Engl J Med, 2022;387:205–216","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Jastreboff+SURMOUNT-1+tirzepatide+2022"},{"citation":"Aronne LJ, Horn DB, le Roux CW, et al. Tirzepatide as compared with semaglutide for the treatment of obesity (SURMOUNT-5).","where":"N Engl J Med, 2025;393(1):26–36","url":"https://pubmed.ncbi.nlm.nih.gov/40353578/"}]}],"regions":[{"region":"European Union","status":"Approved, prescription-only","note":"Mounjaro is authorised by the EMA for type 2 diabetes and weight management."},{"region":"United States","status":"Approved, prescription-only","note":"Mounjaro (diabetes), Zepbound (obesity, sleep apnoea). Compounded copies were permitted during shortage and are now restricted."},{"region":"United Kingdom","status":"Approved, prescription-only","note":"NHS rollout for obesity began in 2025 under eligibility criteria."},{"region":"Sweden","status":"Approved, prescription-only","note":"Subsidy differs between diabetes and weight-management use."}],"faq":[{"q":"Is tirzepatide better than semaglutide for weight loss?","a":"On the only head-to-head trial, yes: 20.2% versus 13.7% average loss at 72 weeks in 751 adults, with fewer people stopping for gut side effects on tirzepatide. Individual response varies a great deal."},{"q":"Is tirzepatide a peptide?","a":"Yes — a 39-amino-acid synthetic peptide based on the GIP hormone, modified to also activate GLP-1 receptors and to last about five days."},{"q":"What are the main side effects?","a":"Nausea, diarrhoea, vomiting and constipation, mostly while the dose is being increased. Rarer but serious: pancreatitis and gallbladder problems. It carries the same thyroid C-cell tumour warning as other GLP-1 drugs, based on rodent findings."},{"q":"Does the weight come back after stopping?","a":"Largely. In SURMOUNT-4, people switched to placebo after 36 weeks regained about half of what they had lost within a year, while those who continued kept losing."}],"references":[{"cite":"Jastreboff AM, et al. Tirzepatide once weekly for the treatment of obesity (SURMOUNT-1).","where":"N Engl J Med, 2022;387:205–216","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Jastreboff+SURMOUNT-1+tirzepatide+2022","note":"2,539 adults; −20.9% at 72 weeks on 15 mg."},{"cite":"Aronne LJ, Horn DB, le Roux CW, et al. Tirzepatide as compared with semaglutide for the treatment of obesity (SURMOUNT-5).","where":"N Engl J Med, 2025;393(1):26–36","url":"https://pubmed.ncbi.nlm.nih.gov/40353578/","note":"751 adults, 72 weeks; −20.2% vs −13.7%; waist −18.4 cm vs −13.0 cm."},{"cite":"Frías JP, et al. Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes (SURPASS-2).","where":"N Engl J Med, 2021;385:503–515","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Frias+SURPASS-2+tirzepatide+semaglutide+2021","note":"1,879 adults; HbA1c and weight vs semaglutide 1 mg."},{"cite":"Malhotra A, et al. Tirzepatide for the treatment of obstructive sleep apnea and obesity (SURMOUNT-OSA).","where":"N Engl J Med, 2024;391:1193–1205","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Malhotra+SURMOUNT-OSA+tirzepatide+2024","note":"Two trials, 469 adults; basis of the sleep-apnoea approval."},{"cite":"Eli Lilly. SURPASS-CVOT topline: tirzepatide vs dulaglutide on cardiovascular outcomes in type 2 diabetes.","where":"Press release, 2025; full publication pending at time of review","url":"https://pubmed.ncbi.nlm.nih.gov/?term=SURPASS-CVOT+tirzepatide+dulaglutide","note":"Non-inferiority met; graded B until peer-reviewed."}],"last_reviewed":"2026-09-02","literature_searched_to":"2026-09-02","changelog":[{"date":"2026-09-02","note":"Full page. Added HbA1c, sleep-apnoea and cardiovascular rows; SURMOUNT-5 head-to-head figures; FAQ and regional status."},{"date":"2026-09-01","note":"Initial publication."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"tesamorelin","name":"Tesamorelin","aliases":["Egrifta","GHRH analogue","TH9507"],"url":"https://lyoresearch.com/compounds/tesamorelin","summary":"Tesamorelin is a synthetic analogue of growth-hormone-releasing hormone, approved in the United States to reduce excess abdominal fat in people with HIV-associated lipodystrophy. In that population it cuts visceral fat by about 15% over six months, and the fat returns when treatment stops. Its use for general fat loss, muscle or anti-ageing rests on extrapolation from that specific group; there are no trials in healthy adults. It is not authorised in the EU.","overall_grade":"B","overall_grade_meaning":"probable, not settled","human_trials":"Several RCTs","regulatory_status":"Approved (Rx, US)","outcomes":[{"outcome":"Visceral fat (HIV lipodystrophy)","grade":"A","grade_meaning":"established in humans","effect_size":"moderate","adverse":false,"human_studies":"2 phase 3 RCTs (n=816)","evidence":"Pooled phase 3: visceral adipose tissue −15.2% at 26 weeks vs +5% on placebo; effect lost within 26 weeks of stopping.","references":[{"citation":"Falutz J, et al. Effects of tesamorelin, a growth hormone-releasing factor, in HIV-infected patients with abdominal fat accumulation: pooled analysis of two phase 3 trials.","where":"J Acquir Immune Defic Syndr, 2010;53:311–322","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Falutz+tesamorelin+pooled+phase+3+2010"}]},{"outcome":"Liver fat (HIV with NAFLD)","grade":"B","grade_meaning":"probable, not settled","effect_size":"moderate","adverse":false,"human_studies":"1 RCT (n=61)","evidence":"Hepatic fat fraction fell by about a third over 12 months vs placebo; a specific population, one trial.","references":[{"citation":"Stanley TL, et al. Effects of tesamorelin on non-alcoholic fatty liver disease in HIV: a randomised, double-blind, placebo-controlled trial.","where":"Lancet HIV, 2019","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Stanley+tesamorelin+NAFLD+HIV+Lancet+HIV+2019"}]},{"outcome":"Cognition in older adults","grade":"C","grade_meaning":"weak human evidence","effect_size":"small","adverse":false,"human_studies":"1 RCT (n=152)","evidence":"20 weeks of tesamorelin improved some executive-function measures in healthy older adults and those with mild cognitive impairment. Single trial, never replicated or developed further.","references":[{"citation":"Baker LD, et al. Effects of growth hormone-releasing hormone on cognitive function in adults with mild cognitive impairment and healthy older adults.","where":"Arch Neurol, 2012;69:1420–1429","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Baker+tesamorelin+cognitive+function+older+adults+2012"}]},{"outcome":"Fat loss in healthy adults","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"None","evidence":"Not studied. The approved population is not a proxy for the general public.","references":[]},{"outcome":"IGF-1 elevation and glucose effects","grade":"A","grade_meaning":"established in humans","effect_size":"small","adverse":true,"human_studies":"Phase 3 programme","evidence":"Raises IGF-1 as intended; small rises in blood glucose and injection-site reactions are documented. Long-term cancer risk at elevated IGF-1 is the reason for the narrow label.","references":[{"citation":"Falutz J, et al. Effects of tesamorelin, a growth hormone-releasing factor, in HIV-infected patients with abdominal fat accumulation: pooled analysis of two phase 3 trials.","where":"J Acquir Immune Defic Syndr, 2010;53:311–322","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Falutz+tesamorelin+pooled+phase+3+2010"}]}],"regions":[{"region":"United States","status":"Approved, prescription-only (narrow indication)","note":"Egrifta, for excess abdominal fat in HIV-associated lipodystrophy only."},{"region":"European Union","status":"Not authorised","note":"The EMA application was withdrawn; no EU marketing authorisation exists."},{"region":"United Kingdom","status":"Not authorised","note":"Not licensed by the MHRA."},{"region":"Sport (WADA)","status":"Prohibited","note":"Growth-hormone-releasing factors are banned at all times."}],"faq":[{"q":"Does tesamorelin burn belly fat?","a":"In people with HIV-associated lipodystrophy, yes — about 15% less visceral fat after six months in two phase 3 trials. In anyone else it has not been tested, and the fat returns when treatment stops."},{"q":"Is tesamorelin the same as growth hormone?","a":"No. It prompts the body to release its own growth hormone rather than supplying it. The downstream effects overlap, including higher IGF-1."},{"q":"Is tesamorelin legal?","a":"It is a prescription medicine in the United States for one indication. It is not authorised in the EU or UK, and it is banned in sport."}],"references":[{"cite":"Falutz J, et al. Effects of tesamorelin, a growth hormone-releasing factor, in HIV-infected patients with abdominal fat accumulation: pooled analysis of two phase 3 trials.","where":"J Acquir Immune Defic Syndr, 2010;53:311–322","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Falutz+tesamorelin+pooled+phase+3+2010","note":"816 participants; the approval basis."},{"cite":"Stanley TL, et al. Effects of tesamorelin on non-alcoholic fatty liver disease in HIV: a randomised, double-blind, placebo-controlled trial.","where":"Lancet HIV, 2019","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Stanley+tesamorelin+NAFLD+HIV+Lancet+HIV+2019","note":"61 participants, 12 months."},{"cite":"Baker LD, et al. Effects of growth hormone-releasing hormone on cognitive function in adults with mild cognitive impairment and healthy older adults.","where":"Arch Neurol, 2012;69:1420–1429","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Baker+tesamorelin+cognitive+function+older+adults+2012","note":"152 adults, 20 weeks; not replicated."}],"last_reviewed":"2026-09-02","literature_searched_to":"2026-09-02","changelog":[{"date":"2026-09-02","note":"Full page. Added liver-fat, cognition and IGF-1 rows; regional status; FAQ."},{"date":"2026-09-01","note":"Initial publication."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"ipamorelin","name":"Ipamorelin","aliases":["GH secretagogue","ghrelin mimetic","NNC 26-0161"],"url":"https://lyoresearch.com/compounds/ipamorelin","summary":"Ipamorelin is a synthetic five-amino-acid peptide that stimulates growth-hormone release with little effect on cortisol or prolactin. Small early studies confirmed the hormone release; the only randomised trial — 117 bowel-surgery patients, testing it for post-operative gut recovery — found no benefit, and development stopped. It is not an approved medicine anywhere, and the popular claims about muscle, fat loss and sleep have never been tested in a trial.","overall_grade":"C","overall_grade_meaning":"weak human evidence","human_trials":"1 RCT (negative) + small early-phase","regulatory_status":"Not approved","outcomes":[{"outcome":"Growth hormone release","grade":"C","grade_meaning":"weak human evidence","effect_size":"moderate","adverse":false,"human_studies":"Small early-phase studies","evidence":"Acute, dose-dependent GH rises demonstrated in healthy volunteers in Novo Nordisk's early programme; more selective than GHRP-6, with little cortisol or prolactin rise.","references":[{"citation":"Raun K, et al. Ipamorelin, the first selective growth hormone secretagogue.","where":"Eur J Endocrinol, 1998;139:552–561","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Raun+ipamorelin+selective+growth+hormone+secretagogue+1998"},{"citation":"Gobburu JV, et al. Pharmacokinetic-pharmacodynamic modeling of ipamorelin, a growth hormone releasing peptide, in human volunteers.","where":"Pharm Res, 1999;16:1412–1416","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Gobburu+ipamorelin+pharmacokinetic+human+volunteers+1999"}]},{"outcome":"Post-operative ileus (gut recovery)","grade":"C","grade_meaning":"weak human evidence","effect_size":"not measurable","adverse":false,"human_studies":"1 RCT (n=117)","evidence":"Median time to tolerate a solid meal 25.3 h vs 32.6 h on placebo — not statistically significant (p=0.15). No difference on secondary endpoints. Phase 3 was not pursued.","references":[{"citation":"Beck DE, Sweeney WB, McCarter MD, et al. Prospective, randomized, controlled, proof-of-concept study of the ghrelin mimetic ipamorelin for the management of postoperative ileus in bowel resection patients.","where":"Int J Colorectal Dis, 2014;29:1527–1534","url":"https://link.springer.com/article/10.1007/s00384-014-2030-8"}]},{"outcome":"Body composition","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"None controlled","evidence":"No trial has measured muscle or fat change in people.","references":[]},{"outcome":"Sleep or recovery","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"None","evidence":"Unstudied in humans.","references":[]},{"outcome":"Safety in humans","grade":"C","grade_meaning":"weak human evidence","effect_size":"not measurable","adverse":true,"human_studies":"1 RCT + early-phase","evidence":"Well tolerated over seven days of IV dosing in the ileus trial. No long-term human safety data at the doses and durations used on the grey market.","references":[{"citation":"Beck DE, Sweeney WB, McCarter MD, et al. Prospective, randomized, controlled, proof-of-concept study of the ghrelin mimetic ipamorelin for the management of postoperative ileus in bowel resection patients.","where":"Int J Colorectal Dis, 2014;29:1527–1534","url":"https://link.springer.com/article/10.1007/s00384-014-2030-8"}]}],"regions":[{"region":"European Union","status":"Unapproved medicinal product","note":"No marketing authorisation. Sale for human use is an offence for the seller."},{"region":"United States","status":"Not approved; compounding restricted","note":"FDA has placed ipamorelin among substances that may present significant safety risks in compounding."},{"region":"Sport (WADA)","status":"Prohibited","note":"Growth-hormone secretagogues are banned at all times."},{"region":"Sweden","status":"Unapproved","note":"Treated as a medicine without authorisation."}],"faq":[{"q":"Does ipamorelin build muscle?","a":"Nobody knows. It releases growth hormone in the short term, but no trial has measured muscle or fat change in people taking it. The claim is an inference from the hormone, not a result."},{"q":"Is ipamorelin safe?","a":"It was well tolerated for a week of intravenous dosing in one trial of surgical patients. There is no human data on months of injections, which is how it is used outside medicine."},{"q":"Why was ipamorelin never approved?","a":"Its one proper randomised trial, for post-operative gut recovery, did not meet its endpoint, and the developer stopped. No company has tested it for any other indication."}],"references":[{"cite":"Raun K, et al. Ipamorelin, the first selective growth hormone secretagogue.","where":"Eur J Endocrinol, 1998;139:552–561","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Raun+ipamorelin+selective+growth+hormone+secretagogue+1998","note":"Pharmacology; animal and early human data."},{"cite":"Gobburu JV, et al. Pharmacokinetic-pharmacodynamic modeling of ipamorelin, a growth hormone releasing peptide, in human volunteers.","where":"Pharm Res, 1999;16:1412–1416","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Gobburu+ipamorelin+pharmacokinetic+human+volunteers+1999","note":"Dose–response for GH release in healthy adults."},{"cite":"Beck DE, Sweeney WB, McCarter MD, et al. Prospective, randomized, controlled, proof-of-concept study of the ghrelin mimetic ipamorelin for the management of postoperative ileus in bowel resection patients.","where":"Int J Colorectal Dis, 2014;29:1527–1534","url":"https://link.springer.com/article/10.1007/s00384-014-2030-8","note":"117 patients; primary endpoint not met (p=0.15)."}],"last_reviewed":"2026-09-02","literature_searched_to":"2026-09-02","changelog":[{"date":"2026-09-02","note":"Full page. Added the negative post-operative-ileus RCT, safety row, regional status and FAQ."},{"date":"2026-09-01","note":"Initial publication."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"ghk-cu","name":"GHK-Cu","aliases":["copper peptide","copper tripeptide-1","glycyl-L-histidyl-L-lysine"],"url":"https://lyoresearch.com/compounds/ghk-cu","summary":"GHK-Cu is a naturally occurring three-amino-acid peptide that binds copper, found in plasma, saliva and urine, with levels that fall with age. Applied to skin in creams it has modest evidence from small trials for improving fine lines and skin firmness, which is why it is a common cosmetic ingredient. Injected use — increasingly promoted online — has no human evidence of any kind.","overall_grade":"C","overall_grade_meaning":"weak human evidence","human_trials":"Small topical trials","regulatory_status":"Cosmetic ingredient","outcomes":[{"outcome":"Skin appearance (topical)","grade":"C","grade_meaning":"weak human evidence","effect_size":"small","adverse":false,"human_studies":"3–4 small trials","evidence":"Twelve-week facial studies in the late 1990s and early 2000s reported improved skin laxity, clarity and fine lines versus vehicle or comparators. Small, short, largely industry-run.","references":[{"citation":"Pickart L, Margolina A. Regenerative and protective actions of the GHK-Cu peptide in the light of the new gene data.","where":"Int J Mol Sci, 2018;19:1987 (review)","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Pickart+Margolina+GHK-Cu+2018+review"},{"citation":"Leyden JJ, et al. Skin care benefits of copper peptide containing facial cream.","where":"American Academy of Dermatology meeting, 2002 (abstract)","url":"https://pubmed.ncbi.nlm.nih.gov/?term=copper+peptide+facial+cream+skin+laxity+12+week"}]},{"outcome":"Wound healing (topical)","grade":"C","grade_meaning":"weak human evidence","effect_size":"small","adverse":false,"human_studies":"Small trials, mixed","evidence":"A GHK-Cu gel was tested on diabetic foot ulcers in the 1990s with mixed results; the product was not carried forward.","references":[{"citation":"Mulder GD, et al. Enhanced healing of ulcers in patients with diabetes by topical treatment with glycyl-L-histidyl-L-lysine copper.","where":"Wound Repair Regen, 1994;2:259–269","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Mulder+glycyl-histidyl-lysine+copper+diabetic+ulcers+1994"}]},{"outcome":"Hair growth","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"None controlled","evidence":"Claims rest on cell and animal work and on analogy with minoxidil; no human trial.","references":[]},{"outcome":"Any outcome (injected)","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"None","evidence":"Unstudied in humans. Injecting a copper complex without data on distribution or dose is not a safety-neutral act.","references":[]}],"regions":[{"region":"European Union","status":"Permitted as a cosmetic ingredient","note":"Listed in the EU cosmetic ingredient inventory. Injectable products are unlicensed medicines."},{"region":"United States","status":"Cosmetic ingredient; injectable unapproved","note":"Legal in topical products. Not approved as a drug; injectable versions are sold as research chemicals."},{"region":"United Kingdom","status":"Cosmetic ingredient","note":"As EU. Injectable use falls under unlicensed medicines rules."},{"region":"Sport (WADA)","status":"Not listed","note":"Not a prohibited substance."}],"faq":[{"q":"Does GHK-Cu work for wrinkles?","a":"Modestly, in small twelve-week studies of topical products — improvements in fine lines, firmness and skin clarity versus vehicle. The trials are small and mostly industry-funded, so the honest answer is “probably a little.”"},{"q":"Is injecting GHK-Cu safe?","a":"Unknown. There are no human studies of injected GHK-Cu. Topical safety data does not transfer to injection."},{"q":"Does GHK-Cu regrow hair?","a":"No human trial has tested it. The claim comes from cell and animal studies and from its structural similarity to how minoxidil is thought to act."}],"references":[{"cite":"Pickart L, Margolina A. Regenerative and protective actions of the GHK-Cu peptide in the light of the new gene data.","where":"Int J Mol Sci, 2018;19:1987 (review)","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Pickart+Margolina+GHK-Cu+2018+review","note":"Review by the peptide's discoverer; declared interest."},{"cite":"Leyden JJ, et al. Skin care benefits of copper peptide containing facial cream.","where":"American Academy of Dermatology meeting, 2002 (abstract)","url":"https://pubmed.ncbi.nlm.nih.gov/?term=copper+peptide+facial+cream+skin+laxity+12+week","note":"Twelve-week facial study; conference abstract, industry-supported."},{"cite":"Mulder GD, et al. Enhanced healing of ulcers in patients with diabetes by topical treatment with glycyl-L-histidyl-L-lysine copper.","where":"Wound Repair Regen, 1994;2:259–269","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Mulder+glycyl-histidyl-lysine+copper+diabetic+ulcers+1994","note":"Small trial of a GHK-Cu gel on diabetic foot ulcers."}],"last_reviewed":"2026-09-02","literature_searched_to":"2026-09-02","changelog":[{"date":"2026-09-02","note":"Full page. Added wound-healing and hair rows, mechanism, regional status and FAQ."},{"date":"2026-09-01","note":"Initial publication."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"epitalon","name":"Epitalon","aliases":["Epithalon","Epithalone","AEDG peptide"],"url":"https://lyoresearch.com/compounds/epitalon","summary":"Epitalon is a synthetic four-amino-acid peptide (Ala-Glu-Asp-Gly) developed in St Petersburg in the 1980s and promoted for longevity on the basis of telomerase activation in cell culture and lifespan effects in mice. The human evidence comes from one research group, is uncontrolled, and much of it used Epithalamin — a pineal-gland extract — rather than the synthetic peptide sold under the name. It is not approved anywhere.","overall_grade":"D","overall_grade_meaning":"no human evidence","human_trials":"Uncontrolled, single group","regulatory_status":"Not approved","outcomes":[{"outcome":"Lifespan / mortality","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"Uncontrolled, single group","evidence":"A 12–15-year observational follow-up of elderly patients from one institute reported lower mortality with Epithalamin (the extract) plus thymus extract. No randomisation, no blinding, and not the synthetic peptide.","references":[{"citation":"Khavinson VKh, Morozov VG. Peptides of pineal gland and thymus prolong human life.","where":"Neuro Endocrinol Lett, 2003;24:233–240","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Khavinson+Morozov+peptides+pineal+thymus+prolong+human+life+2003"}]},{"outcome":"Telomerase activation","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"Cell culture only","evidence":"Telomerase activity and telomere lengthening reported in cultured human fibroblasts. Never measured in a living person.","references":[{"citation":"Khavinson VKh, et al. Peptide promotes overcoming of the division limit in human somatic cell.","where":"Bull Exp Biol Med, 2003;135:503–506","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Khavinson+epitalon+telomerase+human+somatic+cell+2003"}]},{"outcome":"Melatonin / sleep","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"Small uncontrolled","evidence":"Small studies from the same group report restored night-time melatonin in elderly subjects; uncontrolled and unreplicated.","references":[{"citation":"Korkushko OV, et al. Geroprotective effect of epithalamine (pineal gland peptide preparation) in elderly subjects with accelerated aging.","where":"Bull Exp Biol Med, 2006;142:356–359","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Korkushko+epithalamine+elderly+accelerated+aging+2006"}]},{"outcome":"Safety in humans","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":true,"human_studies":"None systematic","evidence":"No adverse-event data collected to modern standards. Unknown is not the same as safe.","references":[]}],"regions":[{"region":"European Union","status":"Unapproved medicinal product","note":"No marketing authorisation anywhere in the EU."},{"region":"United States","status":"Not approved","note":"Sold as a research chemical; not approved as a drug or supplement ingredient."},{"region":"Russia","status":"Extract registered; peptide status unclear","note":"Epithalamin (the extract) has a Russian registration; the synthetic peptide's status is not equivalent."},{"region":"Sweden","status":"Unapproved","note":"Treated as a medicine without authorisation."}],"faq":[{"q":"Does epitalon extend lifespan?","a":"In mice, some studies from one group report modest lifespan effects. In humans there is no controlled evidence. The often-cited 12–15-year follow-up used Epithalamin, a pineal extract, not the synthetic peptide, and had no control group."},{"q":"Does epitalon lengthen telomeres?","a":"In cultured cells, one group has reported telomerase activation. It has never been measured in people taking the peptide."},{"q":"Is epitalon safe?","a":"Unknown. No systematic safety data exist. If it did activate telomerase in vivo, that would be a reason for caution, not reassurance."}],"references":[{"cite":"Khavinson VKh, Morozov VG. Peptides of pineal gland and thymus prolong human life.","where":"Neuro Endocrinol Lett, 2003;24:233–240","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Khavinson+Morozov+peptides+pineal+thymus+prolong+human+life+2003","note":"Uncontrolled long-term observation with Epithalamin (extract) and Thymalin."},{"cite":"Khavinson VKh, et al. Peptide promotes overcoming of the division limit in human somatic cell.","where":"Bull Exp Biol Med, 2003;135:503–506","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Khavinson+epitalon+telomerase+human+somatic+cell+2003","note":"Cell-culture telomerase and telomere findings."},{"cite":"Korkushko OV, et al. Geroprotective effect of epithalamine (pineal gland peptide preparation) in elderly subjects with accelerated aging.","where":"Bull Exp Biol Med, 2006;142:356–359","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Korkushko+epithalamine+elderly+accelerated+aging+2006","note":"Uncontrolled; Epithalamin extract, not the synthetic peptide."}],"last_reviewed":"2026-09-02","literature_searched_to":"2026-09-02","changelog":[{"date":"2026-09-02","note":"Full page. Separated evidence for the synthetic peptide from evidence for the Epithalamin extract; added telomerase, melatonin and safety rows."},{"date":"2026-09-01","note":"Initial publication."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"}]}