{"id":"amycretin","name":"Amycretin","aliases":["Zenagamtide (INN)","GLP-1 and amylin co-agonist","unimolecular GLP-1/amylin receptor agonist"],"url":"https://lyoresearch.com/compounds/amycretin","class":{"id":"glp-1-agonists","name":"GLP-1 and incretin agonists","url":"https://lyoresearch.com/classes/glp-1-agonists"},"summary":"Amycretin is a single molecule that activates both the GLP-1 and the amylin receptor, combining the two mechanisms that CagriSema delivers as two drugs. Its international name is now zenagamtide. In the first published trial — a phase 1b/2a study in 125 people — the highest dose produced 24.3% weight loss at 36 weeks: the largest figure reported for any weight-loss drug at this stage, from a small, early trial in which many participants withdrew. Two phase 2 trials in type 2 diabetes, published in The Lancet in 2026, add a dose-dependent HbA1c reduction of up to 1.7 points; the weight-loss figure has not yet been repeated in a larger trial.","overall_grade":"C","overall_grade_meaning":"weak human evidence","human_trials":"1 phase 1b/2a RCT (n=125); 2 phase 2 RCTs in type 2 diabetes","regulatory_status":"Investigational (early phase)","molecule":{"formula":null,"molecular_weight":null,"cas":null,"pubchem_cid":null,"note":"No PubChem Compound record at review (investigational; zenagamtide)"},"pharmacokinetics":{"basis":"human","route":"Subcutaneous once weekly and oral once daily in the trials","half_life":"Dose-proportional exposure reported; no half-life figure in the accessible abstracts","licensed_regimen":null,"product":null,"source":{"title":"Gasiorek A, et al. Safety, tolerability, pharmacokinetics and pharmacodynamics of the first-in-class GLP-1 and amylin receptor agonist amycretin: a first-in-human phase 1 trial. Lancet 2025;406:135–148","url":"https://www.sciencedirect.com/science/article/abs/pii/S0140673625011766"}},"outcomes":[{"outcome":"Body weight","grade":"C","grade_meaning":"weak human evidence","effect_size":"large","adverse":false,"human_studies":"1 phase 1b/2a RCT (n=125)","evidence":"Doses were escalated over 20–36 weeks. At the top 60 mg dose, weight fell 24.3% against 1.1% on placebo. Substantial numbers of participants withdrew, mostly for reasons unrelated to side effects, which limits how much weight the figure carries.","references":[{"citation":"Dahl K, et al. Amycretin, a novel, unimolecular GLP-1 and amylin receptor agonist administered subcutaneously: results from a phase 1b/2a randomised controlled study.","where":"Lancet, 2025;406:149–162","url":"https://pubmed.ncbi.nlm.nih.gov/40550231/"}],"verbatim":{"text":"Estimated mean bodyweight change from baseline was significantly (Parts A-D: p<0·0001; Part E: p=0·0003) higher with amycretin versus placebo in Part B (60 mg, -24·3% vs -1·1%; week 36), Part C (20 mg, -22·0% vs 1·9%; week 36), Part D (5 mg, -16·2% vs 2·3%; week 28), and Part E (1·25 mg, -9·7% vs 2·0%; week 20).","citation":"Dahl K, et al. Amycretin, a novel, unimolecular GLP-1 and amylin receptor agonist administered subcutaneously: results from a phase 1b/2a randomised controlled study.","url":"https://pubmed.ncbi.nlm.nih.gov/40550231/"}},{"outcome":"Blood glucose (HbA1c) in type 2 diabetes","grade":"B","grade_meaning":"probable, not settled","effect_size":"large","adverse":false,"human_studies":"1 phase 2 RCT (n=262); oral companion trial","evidence":"A 36-week dose-finding trial of the weekly injection in adults with type 2 diabetes on metformin. HbA1c fell by 0.9 to 1.7 points across six doses, against placebo. A once-daily oral formulation was tested in a parallel trial. Both published in The Lancet, 2026.","references":[{"citation":"Mora P, et al. Efficacy and safety of once-weekly subcutaneous zenagamtide, a novel unimolecular GLP-1 and amylin receptor agonist, in type 2 diabetes: a multicentre, randomised, parallel, double-blind, placebo-controlled, dose-finding, phase 2 trial.","where":"Lancet, 2026","url":"https://pubmed.ncbi.nlm.nih.gov/42532080/"},{"citation":"Mora P, et al. Efficacy and safety of once-daily oral zenagamtide, a novel unimolecular GLP-1 and amylin receptor agonist, in adults with type 2 diabetes: a multicentre, randomised, parallel, double-blind, placebo-controlled, dose-finding, phase 2 trial.","where":"Lancet, 2026","url":"https://pubmed.ncbi.nlm.nih.gov/42532079/"}],"verbatim":{"text":"At week 36, estimated change in HbA1c (mean across all groups at baseline 7·8% [SD 0·8]) ranged from -0·9% with zenagamtide 0·4 mg (estimated treatment difference vs placebo: -0·77% [95% CI -1·26 to -0·28]; p=0·0021) to -1·7% with zenagamtide 40 mg (-1·56% [-2·05 to -1·07]; p<0·0001).","citation":"Mora P, et al. Efficacy and safety of once-weekly subcutaneous zenagamtide, a novel unimolecular GLP-1 and amylin receptor agonist, in type 2 diabetes: a multicentre, randomised, parallel, double-blind, placebo-controlled, dose-finding, phase 2 trial.","url":"https://pubmed.ncbi.nlm.nih.gov/42532080/"}},{"outcome":"Trial retention","grade":"C","grade_meaning":"weak human evidence","effect_size":"moderate","adverse":true,"human_studies":"1 phase 1b/2a RCT","evidence":"The trial reports a high withdrawal rate. Because dropouts were largely for reasons unrelated to adverse events, the remaining participants may not represent everyone who started — the standard caution for an early-phase efficacy figure.","references":[{"citation":"Dahl K, et al. Amycretin, a novel, unimolecular GLP-1 and amylin receptor agonist administered subcutaneously: results from a phase 1b/2a randomised controlled study.","where":"Lancet, 2025;406:149–162","url":"https://pubmed.ncbi.nlm.nih.gov/40550231/"}],"verbatim":{"text":"A large number of participants withdrew from the study, with a high proportion of discontinuations occurring due to reasons unrelated to treatment-emergent adverse events.","citation":"Dahl K, et al. Amycretin, a novel, unimolecular GLP-1 and amylin receptor agonist administered subcutaneously: results from a phase 1b/2a randomised controlled study.","url":"https://pubmed.ncbi.nlm.nih.gov/40550231/"}},{"outcome":"GI side effects","grade":"C","grade_meaning":"weak human evidence","effect_size":"moderate","adverse":true,"human_studies":"1 phase 1b/2a RCT","evidence":"Gastrointestinal events were frequent, as with every drug in this class, and mostly resolved.","references":[{"citation":"Dahl K, et al. Amycretin, a novel, unimolecular GLP-1 and amylin receptor agonist administered subcutaneously: results from a phase 1b/2a randomised controlled study.","where":"Lancet, 2025;406:149–162","url":"https://pubmed.ncbi.nlm.nih.gov/40550231/"}],"verbatim":{"text":"The most common treatment-emergent adverse events were gastrointestinal, and the majority were mild to moderate in severity and resolved by the end of the study.","citation":"Dahl K, et al. Amycretin, a novel, unimolecular GLP-1 and amylin receptor agonist administered subcutaneously: results from a phase 1b/2a randomised controlled study.","url":"https://pubmed.ncbi.nlm.nih.gov/40550231/"}}],"regions":[{"region":"European Union","status":"Not authorised","note":"Investigational; no EMA authorisation."},{"region":"United States","status":"Not approved","note":"Investigational. Products sold under this name are not the trial drug."},{"region":"United Kingdom","status":"Not licensed","note":"No MHRA licence."},{"region":"Australia","status":"Not on the ARTG","note":"Investigational only."},{"region":"Canada","status":"Not authorised","note":"No Drug Identification Number."},{"region":"Sport (WADA)","status":"Not prohibited","note":"Not named on the 2026 Prohibited List."}],"faq":[{"q":"Is amycretin really better than tirzepatide?","a":"Unknown. Its 24% figure comes from a phase 1b/2a trial in 125 people with heavy dropout; tirzepatide's 21% comes from a 2,539-person phase 3. Those are not comparable levels of evidence, and no head-to-head exists."},{"q":"How is it different from CagriSema?","a":"CagriSema is two molecules given together — cagrilintide plus semaglutide. Amycretin is one molecule doing both jobs."}],"references":[{"cite":"Dahl K, et al. Amycretin, a novel, unimolecular GLP-1 and amylin receptor agonist administered subcutaneously: results from a phase 1b/2a randomised controlled study.","where":"Lancet, 2025;406:149–162","url":"https://pubmed.ncbi.nlm.nih.gov/40550231/","note":"125 participants; up to 36 weeks. NCT06064006."},{"cite":"Mora P, et al. Efficacy and safety of once-weekly subcutaneous zenagamtide, a novel unimolecular GLP-1 and amylin receptor agonist, in type 2 diabetes: a multicentre, randomised, parallel, double-blind, placebo-controlled, dose-finding, phase 2 trial.","where":"Lancet, 2026","url":"https://pubmed.ncbi.nlm.nih.gov/42532080/","note":"262 randomised, 36 weeks, six doses. NCT06542874."},{"cite":"Mora P, et al. Efficacy and safety of once-daily oral zenagamtide, a novel unimolecular GLP-1 and amylin receptor agonist, in adults with type 2 diabetes: a multicentre, randomised, parallel, double-blind, placebo-controlled, dose-finding, phase 2 trial.","where":"Lancet, 2026","url":"https://pubmed.ncbi.nlm.nih.gov/42532079/","note":"Oral companion trial."}],"last_reviewed":"2026-09-23","literature_searched_to":"2026-09-23","changelog":[{"date":"2026-09-23","note":"Name zenagamtide added. Two phase 2 trials in type 2 diabetes (Lancet, 2026) added with a verbatim primary result; new HbA1c row at B. Overall grade held at C: the weight-loss figure still rests on the 125-person early-phase trial."},{"date":"2026-09-03","note":"Initial publication from the phase 1b/2a Lancet report. Grade C for trial stage and retention."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"}