Survodutide
A once-weekly glucagon and GLP-1 receptor dual agonist: in phase 3 it cut body weight by about 13% at 76 weeks and in phase 2 it cleared liver inflammation in MASH, but it is not approved anywhere yet.
Survodutide (BI 456906) is Boehringer Ingelheim's injectable peptide that activates two receptors at once: GLP-1, like semaglutide, and glucagon, which raises energy use and acts strongly on the liver. Its first phase 3 obesity trial and a phase 3 liver-fat trial met their goals in 2026, and a heart-safety trial is under way. Until a regulator approves it, it is available only in clinical trials.
What is it?
Survodutide is modelled on oxyntomodulin, a gut hormone that activates both the GLP-1 receptor and the glucagon receptor. GLP-1 signalling reduces appetite and slows the stomach; glucagon signalling raises energy expenditure and pushes the liver to burn fat. Boehringer Ingelheim's scientists attached a C18 fatty acid so the peptide rides on albumin in the blood and lasts long enough for weekly injections. In mice it produced more weight loss than the highest effective dose of semaglutide, through both lower food intake and higher energy use.
In people it has moved quickly through trials. Phase 1 studies in healthy volunteers and people with overweight found dose-dependent weight loss of up to about 14% in 16 weeks, with nausea, vomiting and reduced appetite limiting how fast the dose could rise. A 46-week phase 2 trial in 387 adults without diabetes reached about 15% weight loss at the top dose on planned treatment, and a 16-week trial in type 2 diabetes lowered HbA1c about as much as semaglutide while reducing weight more at higher doses.
The liver is where glucagon agonism is expected to add the most. In a 48-week phase 2 trial in biopsy-confirmed MASH, up to 62% of people on survodutide had their steatohepatitis improve without worsening fibrosis, against 14% on placebo. A 2026 phase 3 trial in obesity with at-risk fatty liver disease met both its liver-fat and weight goals, and a study in people with cirrhosis found blood levels were similar to healthy people and the drug was generally tolerable.
The first phase 3 obesity trial, SYNCHRONIZE-1, reported in 2026: 13.0% weight loss at 76 weeks on the 6.0 mg dose against 5.4% on placebo under the treatment-regimen estimand, with gastrointestinal side effects in about 90% of that dose group. FDA granted survodutide Fast Track designation in 2021 and Breakthrough Therapy designation in 2024, but as of September 27, 2026 it is investigational and not approved anywhere. Anything sold online as survodutide is an unregulated research chemical.
Mechanism of Action
Survodutide activates two receptors. The GLP-1 half works like semaglutide on appetite and blood sugar; the glucagon half adds energy expenditure and a direct push on the liver to use fat. Its trials measured the glucagon effect indirectly, through falling amino acids and liver markers.
GLP-1 receptor: appetite and stomach emptying
In phase 1, paracetamol absorption slowed in the first week, a sign of delayed stomach emptying, and decreased appetite was the commonest effect. In type 2 diabetes, HbA1c fell about as much as with semaglutide.
Glucagon receptor: energy expenditure
In mice, weight loss beyond semaglutide came from higher energy expenditure as well as lower food intake. In people, falling plasma amino acids were the marker that the glucagon receptor was engaged.
Liver fat and inflammation
Glucagon acts directly on the liver. In phase 2 up to 67% had liver fat fall by at least 30%, and in phase 3 84% of treated patients reached that threshold against 24% on placebo.
Insulin sensitivity
A post hoc analysis of two phase 2 trials found better insulin sensitivity and beta-cell markers, largely explained by weight loss rather than a separate effect.
Published Research
Our evidence set holds 38 papers that name survodutide or BI 456906. Twenty-three name it in their titles and have an abstract; 15 are carded below, covering every trial with results and the preclinical work: 12 studies in people, 2 in animals and 1 review. Trial designs without results and meta-analyses of the same trials are left out. Nearly all of the human studies were run and funded by Boehringer Ingelheim.
Discovery and preclinical pharmacology
BI 456906 is an acylated peptide carrying a C18 fatty acid to allow weekly dosing. In mice, pharmacological doses reduced body weight more than maximally effective doses of semaglutide, through both higher energy expenditure and lower food intake. Knockout and reporter mice confirmed activity at both the GLP-1 and glucagon receptors.
Phase 1 in 149 volunteers
A single-rising-dose study in 24 men and a multiple-rising-dose study in 125 adults with a BMI of 27 to 40 found weight fell with dose, by up to 13.8% placebo-corrected at 16 weeks. Falling amino acids and glucagon confirmed both receptors were engaged. Side effects rose with dose; faster escalation led 12.5% to stop, most often for cardiac or vascular events, and slower escalation 17.8%, mostly for gastrointestinal effects.
Phase 1 in Japanese men
Thirty-six Japanese men with overweight or obesity had doses escalated over 16 weeks. Placebo-corrected weight fell by 5.6%, 12.4% and 9.6% in the three dose groups, but 37% of treated men stopped escalating, mostly for decreased appetite. Paracetamol absorption slowed in week one, showing transient delayed stomach emptying.
Phase 2 obesity trial, 387 adults
Adults with a BMI of 27 or more and no diabetes took 0.6, 2.4, 3.6 or 4.8 mg weekly or placebo for 46 weeks. On planned treatment, weight fell 6.2%, 12.5%, 13.2% and 14.9% against 2.8% on placebo. Adverse events, mainly gastrointestinal, affected 91% on survodutide and 75% on placebo, and 61% of both groups completed treatment.
Type 2 diabetes vs semaglutide, 413 adults
People with type 2 diabetes on metformin took one of six survodutide regimens, placebo or semaglutide for 16 weeks. HbA1c fell by up to 1.71 percentage points; a low survodutide dose matched semaglutide's 1.47-point fall. Weight fell by up to 8.7%, more than semaglutide's 5.3% at doses of 1.8 mg a week or more, and adverse events were commoner (77.8% vs 52.0%).
Phase 2 in MASH and fibrosis, 293 adults
In biopsy-confirmed MASH with fibrosis stages F1 to F3, steatohepatitis improved without fibrosis worsening in 47%, 62% and 43% on 2.4, 4.8 and 6.0 mg, against 14% on placebo, after 48 weeks. Liver fat fell by at least 30% in 57 to 67% (14% on placebo) and fibrosis improved by a stage in 34 to 36% (22%). Nausea, diarrhoea and vomiting were much commoner than on placebo.
People with cirrhosis
In an open-label phase 1 trial, single doses gave similar blood levels in people with Child-Pugh A, B or C cirrhosis and matched healthy people, so no dose adjustment was needed. Over 28 weeks of escalation to 6.0 mg, drug-related side effects affected about 82 to 88%, and liver fat, liver stiffness and weight generally fell.
Choosing the clinical candidate
From 19 dual agonists, in vivo markers of GLP-1-receptor engagement (oral glucose tolerance) and glucagon-receptor engagement (FGF21 and liver NNMT) tracked each compound's cell-based potency. Survodutide and two others improved glucose tolerance about as much as semaglutide while engaging the glucagon receptor to different degrees, and were profiled further in obese and diabetic mice before survodutide was chosen.
Survodutide in MASH
A review of survodutide's pharmacology and phase 1 and 2 data in MASH. GLP-1 agonists help steatohepatitis through weight and glucose lowering but have not been shown to reverse fibrosis; the authors argue that adding glucagon-receptor agonism may, and describe the drug as generally well tolerated apart from manageable gastrointestinal effects.
Phase 2 by sex and BMI
In the 387-person phase 2 trial, women lost more weight and waist than men over 46 weeks, and people with a lower starting BMI lost a larger share of their weight, though the waist trend ran the other way. Adverse event rates were similar across subgroups, with nausea the commonest gastrointestinal effect in all of them.
SYNCHRONIZE-1: phase 3 in obesity
725 adults with obesity or overweight and a complication, without diabetes, took up to 3.6 or 6.0 mg weekly or placebo with lifestyle counselling. At 76 weeks weight fell 12.2% and 13.0% against 5.4% on placebo (treatment-regimen estimand), and 72.6%, 71.9% and 46.3% lost at least 5%. Gastrointestinal events affected 80.9%, 89.7% and 47.9%; no deaths were reported.
SYNCHRONIZE-MASLD: phase 3 liver fat
216 adults with obesity and fatty liver disease with inflammation or fibrosis took 6.0 mg weekly or placebo for 48 weeks. Liver fat fell by at least 30% in 84.2% against 24.3% (68.5% vs 28.6% on the treatment-regimen estimand), and weight by 12.2% against 1.0% (8.7% vs 1.4%). Gastrointestinal effects, mostly during escalation, were the commonest.
SYNCHRONIZE: who was enrolled
The 725 SYNCHRONIZE-1 participants from 14 countries averaged 47 years old, BMI 37.9 and waist 115 cm; 59% were women. Common complications were high blood pressure (40%), abnormal lipids (34%) and prediabetes (30%); mean HbA1c was 5.5%.
SYNCHRONIZE-2: people with diabetes
SYNCHRONIZE-2 enrolled 752 adults with type 2 diabetes and a BMI of 27 or more at 133 sites in 19 countries: mean age 55.7, BMI 36.5, HbA1c 7.4%, with high blood pressure in 69% and abnormal lipids in 68%. Its 76-week efficacy results are not in our evidence set.
Beta-cell function and insulin sensitivity
A post hoc analysis of two phase 2 trials (413 people with diabetes, 387 without) found survodutide raised a beta-cell function index and lowered insulin resistance, glucagon and fasting glucose in diabetes, and lowered insulin resistance and fasting insulin without diabetes. Weight change explained the largest share of the insulin-sensitivity changes.
Phase 3 SYNCHRONIZE-2 in type 2 diabetes
In 752 adults with type 2 diabetes and a BMI of 27 or more, weekly survodutide at 3.6 mg or 6.0 mg lowered weight by 8.2% and 9.8% at 76 weeks under the treatment-regimen estimand, which counts everyone randomised, against 3.9% on placebo; 57.6% and 64.5% lost at least 5%, against 35.1%. HbA1c fell 0.9 and 0.8 points from 7.4%, against 0.2. Gastrointestinal events, mostly mild to moderate and transient, affected 72.8% and 77.7%, against 38.6% on placebo.
Dosing Data
Survodutide has no approved dose. In the trials it was injected under the skin once a week and escalated gradually over 16 to 24 weeks to limit nausea and vomiting, reaching maintenance doses of 2.4 to 6.0 mg; the phase 3 obesity trial tested 3.6 mg and 6.0 mg.
Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
→ Full Survodutide dosage guide — how the trials escalated the weekly dose and why slower escalation mattered
Side Effects & Contraindications
Reported Side Effects
From the phase 1 to phase 3 trials above.
Contraindications & Cautions
No approved label exists yet. These cautions follow from the trials and the drug's class.
Legal Status
Survodutide is investigational in every country. It can be used lawfully only in a registered clinical trial.
Frequently Asked Questions
?How much weight did people lose on survodutide?
In the phase 3 SYNCHRONIZE-1 trial, 13.0% on 6.0 mg and 12.2% on 3.6 mg at 76 weeks, against 5.4% on placebo, counting people who stopped treatment. In the phase 2 trial, up to 14.9% at 46 weeks on planned treatment.
?How is survodutide different from semaglutide or tirzepatide?
Semaglutide activates only the GLP-1 receptor and tirzepatide adds GIP. Survodutide adds glucagon instead, which raises energy expenditure and acts directly on the liver, which is why it is also being developed for MASH.
?Is survodutide approved?
No. As of September 27, 2026 it is investigational everywhere. It has FDA Fast Track (2021) and Breakthrough Therapy (2024) designations, which speed review but are not approval.
?What are the side effects?
Mainly nausea, vomiting and diarrhoea, which affected about 90% of people on the 6.0 mg dose in phase 3, mostly while the dose was being increased. Decreased appetite and, in one fast-escalation cohort, cardiac or vascular adverse events led some to stop.
?Does survodutide help fatty liver disease?
In a phase 2 trial, MASH improved without fibrosis worsening in up to 62% against 14% on placebo, and in a phase 3 trial liver fat fell by at least 30% in 84% against 24%. Longer trials of liver outcomes are still running.
?Is survodutide a peptide?
Yes: a synthetic peptide modelled on the gut hormone oxyntomodulin, with a C18 fatty acid attached so it lasts long enough for weekly injections.
References
- [Animal] Zimmermann T, et al. "BI 456906: Discovery and preclinical pharmacology of a novel GCGR/GLP-1R dual agonist with robust anti-obesity efficacy." Mol Metab, 2022;66:101633. PMID: 36356832.
- [Human] Jungnik A, et al. "Phase I studies of the safety, tolerability, pharmacokinetics and pharmacodynamics of the dual glucagon receptor/glucagon-like peptide-1 receptor agonist BI 456906." Diabetes Obes Metab, 2023;25(4):1011-1023. PMID: 36527386.
- [Human] Yazawa R, et al. "A randomized Phase I study of the safety, tolerability, pharmacokinetics and pharmacodynamics of BI 456906, a dual glucagon receptor/glucagon-like peptide-1 receptor agonist, in healthy Japanese men with overweight/obesity." Diabetes Obes Metab, 2023;25(7):1973-1984. PMID: 36974349.
- [Human] 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." Lancet Diabetes Endocrinol, 2024;12(3):162-173. PMID: 38330987.
- [Human] Blüher M, et al. "Dose-response effects on HbA(1c) and bodyweight reduction of survodutide, a dual glucagon/GLP-1 receptor agonist, compared with placebo and open-label semaglutide in people with type 2 diabetes: a randomised clinical trial." Diabetologia, 2024;67(3):470-482. PMID: 38095657.
- [Human] Sanyal AJ, et al. "A Phase 2 Randomized Trial of Survodutide in MASH and Fibrosis." N Engl J Med, 2024;391(4):311-319. PMID: 38847460.
- [Human] Lawitz EJ, et al. "Efficacy, tolerability and pharmacokinetics of survodutide, a glucagon/glucagon-like peptide-1 receptor dual agonist, in cirrhosis." J Hepatol, 2024;81(5):837-846. PMID: 38857788.
- [Animal] Thomas L, et al. "The dual GCGR/GLP-1R agonist survodutide: Biomarkers and pharmacological profiling for clinical candidate selection." Diabetes Obes Metab, 2024;26(6):2368-2378. PMID: 38560764.
- [Review] Kaya E, et al. "Survodutide in MASH: bridging the gap between hepatic and systemic metabolic dysfunction." Expert Opin Investig Drugs, 2024;33(12):1167-1176. PMID: 39663847.
- [Human] le Roux CW, et al. "Subgroup analysis by sex and baseline BMI in people with a BMI ≥27 kg/m(2) in the phase 2 trial of survodutide, a glucagon/GLP-1 receptor dual agonist." Diabetes Obes Metab, 2025;27(4):1773-1782. PMID: 39821928.
- [Human] le Roux CW, et al. "Survodutide Once Weekly for the Treatment of Adults with Obesity." N Engl J Med, 2026;395(8):776-787. PMID: 42253238.
- [Human] Kaplan LM, et al. "Survodutide in adults with obesity and metabolic dysfunction-associated steatotic liver disease: SYNCHRONIZE-MASLD, a randomized, double-blind, placebo-controlled phase 3 trial." Nat Med, 2026;32(8):2948-2958. PMID: 42252333.
- [Human] le Roux CW, et al. "Survodutide for treatment of obesity: Baseline characteristics of participants in a randomized, double-blind, placebo-controlled, phase 3 trial (SYNCHRONIZE™-1)." Diabetes Obes Metab, 2026;28(1):337-346. PMID: 41187967.
- [Human] Wharton S, et al. "Baseline characteristics in the SYNCHRONIZE™-2 randomized phase 3 trial of survodutide, a glucagon receptor/GLP-1 receptor dual agonist, for obesity in people with type 2 diabetes." Diabetes Obes Metab, 2026;28(2):1490-1498. PMID: 41216778.
- [Human] Ekinci EI, et al. "Dual Glucagon and GLP-1 Receptor Agonist Survodutide Improves Biomarkers of Beta-Cell Function and Insulin Sensitivity in People With Type 2 Diabetes or Living With Overweight/Obesity." Diabetes Obes Metab, 2026;28(9):8242-8253. PMID: 42331726.
- [clinical-trial] Boehringer Ingelheim. SYNCHRONIZE-1: survodutide in adults with obesity without type 2 diabetes (phase 3). ClinicalTrials.gov NCT06066515; results published 2026.
- [Human] Wharton S, et al. "Survodutide Once Weekly in Adults with Obesity and Type 2 Diabetes." N Engl J Med, 2026. PMID: 42820639.
Sources & Citations
Every citation on this page is PubMed-indexed and has been checked against its record, except the trial registration. Regulatory designations are as Boehringer Ingelheim reported them. Grey Peptides sells nothing and links to no vendor.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.