{"id":"survodutide","name":"Survodutide","aliases":["BI 456906","GLP-1/glucagon dual agonist","Boehringer Ingelheim / Zealand"],"url":"https://lyoresearch.com/compounds/survodutide","class":{"id":"glp-1-agonists","name":"GLP-1 and incretin agonists","url":"https://lyoresearch.com/classes/glp-1-agonists"},"summary":"Survodutide is a once-weekly peptide that activates both the GLP-1 and glucagon receptors. In SYNCHRONIZE-1, a 725-person phase 3 trial published in June 2026, it produced 12–13% weight loss at 76 weeks against 5% on placebo, with gastrointestinal symptoms in up to 90% of participants. In people who also have type 2 diabetes the figure was 8–10% against 4% (SYNCHRONIZE-2, published October 2026). Its distinctive result is in the liver: a phase 2 trial resolved MASH without worsening fibrosis in 83% of patients at the top dose. It is not approved anywhere.","overall_grade":"B","overall_grade_meaning":"probable, not settled","human_trials":"2 phase 3 RCTs published (n=725; n=752)","regulatory_status":"Investigational","molecule":{"formula":"C192H289N47O61","molecular_weight":"4232","cas":"2805997-46-8","pubchem_cid":171378821,"note":null},"pharmacokinetics":{"basis":"human","route":"Subcutaneous, once weekly","half_life":"About 6 days","licensed_regimen":null,"product":null,"source":{"title":"Lawitz EJ, et al. Efficacy, tolerability and pharmacokinetics of survodutide in cirrhosis. J Hepatol 2024;81","url":"https://www.sciencedirect.com/science/article/pii/S0168827824023031"}},"outcomes":[{"outcome":"Body weight","grade":"B","grade_meaning":"probable, not settled","effect_size":"moderate","adverse":false,"human_studies":"1 phase 3 RCT + phase 2","evidence":"SYNCHRONIZE-1, 725 adults, 76 weeks: −12% (3.6 mg) and −13% (6.0 mg) versus −5% placebo; at least 5% loss in 73%, 72% and 46%. Phase 2: up to −14.9% at 46 weeks.","references":[{"citation":"Survodutide in adults with obesity: SYNCHRONIZE-1, a randomised, double-blind, placebo-controlled phase 3 trial.","where":"N Engl J Med, published online 7 June 2026","url":"https://pubmed.ncbi.nlm.nih.gov/?term=survodutide+SYNCHRONIZE-1"},{"citation":"le Roux CW, et al. Glucagon and GLP-1 receptor dual agonist survodutide for obesity: a randomised, double-blind, placebo-controlled, dose-finding phase 2 trial.","where":"Lancet Diabetes Endocrinol, 2024","url":"https://pubmed.ncbi.nlm.nih.gov/?term=survodutide+obesity+phase+2+le+Roux"}],"verbatim":{"text":"At week 76, the mean change in body weight from baseline according to the treatment-regimen estimand was -12.2% (95% confidence interval [CI], -13.6 to -10.8) in the 3.6-mg group, -13.0% (95% CI, -14.4 to -11.6) in the 6.0-mg group, and -5.4% (95% CI, -6.9 to -4.0) in the placebo group; 72.6%, 71.9% and 46.3% of the participants, respectively, had weight reduction of at least 5% (P<0.001 for all comparisons with placebo).","citation":"Survodutide in adults with obesity: SYNCHRONIZE-1, a randomised, double-blind, placebo-controlled phase 3 trial.","url":"https://pubmed.ncbi.nlm.nih.gov/?term=survodutide+SYNCHRONIZE-1"}},{"outcome":"Body weight (obesity with type 2 diabetes)","grade":"B","grade_meaning":"probable, not settled","effect_size":"moderate","adverse":false,"human_studies":"1 phase 3 RCT (n=752, 76 wk)","evidence":"SYNCHRONIZE-2, published in the New England Journal of Medicine on 1 October 2026: −8.2% (3.6 mg) and −9.8% (6.0 mg) versus −3.9% on placebo at 76 weeks, counting all participants whether or not they stayed on treatment; at least 5% loss in 57.6%, 64.5% and 35.1%. HbA1c fell 0.9 and 0.8 points against 0.2, from a baseline of 7.4%. The usual pattern: less weight loss when type 2 diabetes is present.","references":[{"citation":"Wharton S, et al. Survodutide once weekly in adults with obesity and type 2 diabetes (SYNCHRONIZE-2).","where":"N Engl J Med, 2026 (online 1 Oct)","url":"https://pubmed.ncbi.nlm.nih.gov/42820639/"}],"verbatim":{"text":"The mean weight change at week 76 according to the treatment-regimen estimand (which assessed effects regardless of whether the trial regimen was discontinued or interrupted or whether other antiobesity therapies were used) was -8.2% (95% confidence interval [CI], -9.2 to -7.2) in the 3.6-mg group, -9.8% (95% CI, -10.8 to -8.8) in the 6.0-mg group, and -3.9% (95% CI, -4.9 to -2.9) in the placebo group; weight reduction of at least 5% occurred in 57.6%, 64.5%, and 35.1% of the participants, respectively (P<0.001 for all comparisons with placebo).","citation":"Wharton S, et al. Survodutide once weekly in adults with obesity and type 2 diabetes (SYNCHRONIZE-2).","url":"https://pubmed.ncbi.nlm.nih.gov/42820639/"}},{"outcome":"Liver disease (MASH resolution)","grade":"B","grade_meaning":"probable, not settled","effect_size":"large","adverse":false,"human_studies":"1 phase 2 RCT; phase 3 running","evidence":"Phase 2 in 293 patients: MASH improvement without worsening fibrosis in 83% at 4.8 mg versus 18% on placebo at 48 weeks; fibrosis improvement in 52% versus 26%. Phase 3 LIVERAGE ongoing.","references":[{"citation":"Sanyal AJ, et al. A phase 2 randomized trial of survodutide in MASH and fibrosis.","where":"N Engl J Med, 2024; DOI 10.1056/NEJMoa2401755","url":"https://www.nejm.org/doi/full/10.1056/NEJMoa2401755"}]},{"outcome":"Liver fat and visceral fat","grade":"B","grade_meaning":"probable, not settled","effect_size":"large","adverse":false,"human_studies":"Phase 3 (SYNCHRONIZE-MASLD)","evidence":"Marked reductions in liver fat and visceral fat reported in the phase 3 obesity-with-MASLD trial; consistent with the glucagon component's hepatic action.","references":[{"citation":"Survodutide in adults with obesity and metabolic dysfunction-associated steatotic liver disease: SYNCHRONIZE-MASLD, a phase 3 trial.","where":"2026","url":"https://pubmed.ncbi.nlm.nih.gov/42252333/"}]},{"outcome":"GI side effects","grade":"B","grade_meaning":"probable, not settled","effect_size":"large","adverse":true,"human_studies":"Phase 3","evidence":"Mild-to-moderate gastrointestinal symptoms in 81% (3.6 mg) and 90% (6.0 mg) versus 48% on placebo in SYNCHRONIZE-1, with substantial discontinuation. SYNCHRONIZE-2: 72.8% and 77.7% versus 38.6%, generally mild to moderate and transient.","references":[{"citation":"Survodutide in adults with obesity: SYNCHRONIZE-1, a randomised, double-blind, placebo-controlled phase 3 trial.","where":"N Engl J Med, published online 7 June 2026","url":"https://pubmed.ncbi.nlm.nih.gov/?term=survodutide+SYNCHRONIZE-1"},{"citation":"Wharton S, et al. Survodutide once weekly in adults with obesity and type 2 diabetes (SYNCHRONIZE-2).","where":"N Engl J Med, 2026 (online 1 Oct)","url":"https://pubmed.ncbi.nlm.nih.gov/42820639/"}]},{"outcome":"Heart rate increase","grade":"B","grade_meaning":"probable, not settled","effect_size":"small","adverse":true,"human_studies":"Phase 2 + 3","evidence":"Resting heart rate rises a few beats per minute, as with other glucagon-receptor agonists; long-term significance unknown.","references":[{"citation":"le Roux CW, et al. Glucagon and GLP-1 receptor dual agonist survodutide for obesity: a randomised, double-blind, placebo-controlled, dose-finding phase 2 trial.","where":"Lancet Diabetes Endocrinol, 2024","url":"https://pubmed.ncbi.nlm.nih.gov/?term=survodutide+obesity+phase+2+le+Roux"}]}],"regions":[{"region":"European Union","status":"Investigational; not authorised","note":"Phase 3; no marketing authorisation. Supply outside trials is unlawful."},{"region":"United States","status":"Investigational; not approved","note":"Phase 3; FDA has warned sellers marketing 'research' survodutide for human use. Cannot be compounded."},{"region":"United Kingdom","status":"Unlicensed","note":"Investigational; supply outside trials is an offence."},{"region":"Australia","status":"Unapproved","note":"Not on the ARTG; no lawful supply outside trials."},{"region":"Canada","status":"Not authorised","note":"Investigational; no DIN."},{"region":"Sport (WADA)","status":"Prohibited at all times","note":"Unapproved anywhere, so it falls under S0 (non-approved substances)."}],"faq":[{"q":"How much weight does survodutide cause people to lose?","a":"In the phase 3 SYNCHRONIZE-1 trial, 12–13% over 76 weeks against 5% on placebo — less than tirzepatide's roughly 20% in its own trials, though trials are not directly comparable."},{"q":"Why is survodutide talked about for liver disease?","a":"Because its glucagon component acts on the liver. In a phase 2 trial, 83% of patients on the top dose had MASH resolve without worsening fibrosis, against 18% on placebo — among the strongest liver results of any drug in the class."},{"q":"Is survodutide available?","a":"No. It is investigational everywhere. The FDA has specifically warned companies selling it as a research chemical for human use."}],"references":[{"cite":"Survodutide in adults with obesity: SYNCHRONIZE-1, a randomised, double-blind, placebo-controlled phase 3 trial.","where":"N Engl J Med, published online 7 June 2026","url":"https://pubmed.ncbi.nlm.nih.gov/?term=survodutide+SYNCHRONIZE-1","note":"725 adults, 76 weeks, 3.6 mg and 6.0 mg versus placebo."},{"cite":"le Roux CW, et al. Glucagon and GLP-1 receptor dual agonist survodutide for obesity: a randomised, double-blind, placebo-controlled, dose-finding phase 2 trial.","where":"Lancet Diabetes Endocrinol, 2024","url":"https://pubmed.ncbi.nlm.nih.gov/?term=survodutide+obesity+phase+2+le+Roux","note":"387 adults, 46 weeks."},{"cite":"Sanyal AJ, et al. A phase 2 randomized trial of survodutide in MASH and fibrosis.","where":"N Engl J Med, 2024; DOI 10.1056/NEJMoa2401755","url":"https://www.nejm.org/doi/full/10.1056/NEJMoa2401755","note":"293 patients, 48 weeks."},{"cite":"Survodutide in adults with obesity and metabolic dysfunction-associated steatotic liver disease: SYNCHRONIZE-MASLD, a phase 3 trial.","where":"2026","url":"https://pubmed.ncbi.nlm.nih.gov/42252333/","note":"Liver-fat and visceral-fat outcomes."},{"cite":"Wharton S, et al. Survodutide once weekly in adults with obesity and type 2 diabetes (SYNCHRONIZE-2).","where":"N Engl J Med, 2026 (online 1 Oct)","url":"https://pubmed.ncbi.nlm.nih.gov/42820639/","note":"752 adults, 76 weeks, 3.6 mg and 6.0 mg versus placebo. NCT06066528."}],"last_reviewed":"2026-10-07","literature_searched_to":"2026-10-07","changelog":[{"date":"2026-10-07","note":"SYNCHRONIZE-2 (N Engl J Med, 1 Oct 2026) added as a new row for obesity with type 2 diabetes, graded B: −8.2% and −9.8% versus −3.9% at 76 weeks. Other grades unchanged."},{"date":"2026-09-03","note":"Initial publication from SYNCHRONIZE-1 and the phase 2 MASH trial."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"}