Survodutide (code name BI 456906) is an investigational once-weekly injectable peptide that activates two hormone receptors: the glucagon receptor and the glucagon-like peptide-1 (GLP-1) receptor. It is licensed to Boehringer Ingelheim from Zealand Pharma, and Boehringer is responsible for its development worldwide (Boehringer Ingelheim press release, October 2024). It is being studied for obesity, type 2 diabetes with obesity, and fatty liver disease.
The single most important fact: survodutide is not approved anywhere. Phase 3 obesity trials reported in 2026, and the FDA has granted it Breakthrough Therapy designation for a form of liver disease called MASH, but no regulator has approved it. Products sold online as “research” survodutide have been named by the FDA as unapproved new drugs.
This page summarizes what the published clinical trials, company disclosures and regulators report. It is for education only and is not medical advice.
| Property | Detail |
|---|---|
| Drug class | Dual glucagon and GLP-1 receptor agonist; long-acting peptide based on glucagon |
| Developer / code | Zealand Pharma (licensor); Boehringer Ingelheim (developer, BI 456906) |
| Approval status | Investigational; not approved by the FDA, EMA or any other regulator |
| Route | Subcutaneous injection once weekly |
| Doses studied | Phase 3: 3.6 mg and 6.0 mg/week; phase 2: 0.3–6.0 mg/week |
| Half-life | Designed for once-weekly dosing via albumin binding; a human half-life value is not reported in the openly available trial publications |
| Molecular formula | C192H289N47O61, about 4,232 g/mol (PubChem) |
| US regulatory designations | Fast Track (May 2021) and Breakthrough Therapy (September 2024) for MASH with stage 2–3 fibrosis |
| US controlled-substance status | Not listed in DEA Schedule III (21 CFR 1308.13) |
| WADA status | Not named on the 2026 List; as an unapproved drug it falls under S0 (non-approved substances) |
What it is
Survodutide is built on the structure of glucagon, the pancreatic hormone that raises blood sugar and acts on the liver. The developers modified it in three main ways (Zimmermann et al., Mol Metab 2022):
- an unnatural amino acid at position 2, the site where the enzyme DPP-4 normally cuts and inactivates glucagon-like peptides;
- changes that add strong GLP-1 receptor activity on top of glucagon receptor activity;
- a C18 fatty diacid (a fat-like chain) attached through a short linker at position 24, which makes the peptide bind albumin in the blood and stay in circulation long enough for weekly dosing.
PubChem lists its formula as C192H289N47O61 (PubChem).
The rationale is the same as for mazdutide: the GLP-1 receptor mainly reduces appetite, while the glucagon receptor acts on the liver and can raise energy expenditure. In the developers’ preclinical work, the following was found in mice (Zimmermann et al., Mol Metab 2022):
- survodutide lowered body weight more than maximally effective doses of semaglutide;
- the extra effect came from both reduced food intake and increased energy expenditure;
- markers of glucagon receptor activity in the liver (such as circulating amino acids and FGF-21) confirmed that both receptors were engaged.
These are animal findings. The human trials below measured weight, liver fat and blood sugar, not energy expenditure.
How it compares with related drugs
| Drug | Receptors activated | Status | Library page |
|---|---|---|---|
| Semaglutide | GLP-1 | Approved (FDA, EMA) | Semaglutide |
| Tirzepatide | GIP and GLP-1 | Approved (FDA, EMA) | Tirzepatide |
| Mazdutide | GLP-1 and glucagon | Approved in China only | Mazdutide |
| Survodutide | Glucagon and GLP-1 | Investigational | This page |
| Retatrutide | GIP, GLP-1 and glucagon | Investigational | Retatrutide |
Survodutide and mazdutide are the two most advanced glucagon/GLP-1 dual agonists. Mazdutide is modeled on oxyntomodulin and was tested mostly in Chinese adults. Survodutide is built on glucagon and its phase 3 trials enrolled multinational populations. The two have not been compared head to head.
Pharmacokinetics
The fatty-acid chain and albumin binding are what allow once-weekly injection (Zimmermann et al., Mol Metab 2022). In phase 1 trials, drug exposure rose with dose (Yazawa et al., Diabetes Obes Metab 2023). In the Japanese phase 1 study, paracetamol absorption fell during week 1 at the higher dose schedules, which indicates a temporary slowing of stomach emptying, a known GLP-1 effect.
A dedicated phase 1 trial gave a single 0.3 mg dose to people with mild, moderate or severe cirrhosis (Child-Pugh A, B or C) and to matched healthy controls (Lawitz et al., J Hepatol 2024). Total exposure and peak levels were similar in both groups, and the authors concluded that no dose adjustment for pharmacokinetic reasons is needed in cirrhosis.
Regulatory status
- Not approved. Boehringer Ingelheim describes survodutide as “an investigational agent” that has not been approved (Boehringer Ingelheim press release, April 28, 2026).
- MASH designations. The FDA granted Fast Track designation in May 2021 and Breakthrough Therapy designation in September 2024 for adults with non-cirrhotic MASH (metabolic dysfunction-associated steatohepatitis, an inflammatory form of fatty liver disease) with moderate or advanced fibrosis (stage 2 or 3). The EMA accepted it into its PRIME scheme in November 2023 (Boehringer Ingelheim press release, October 2024). These designations speed up development and review. They are not approvals.
- FDA enforcement. An FDA warning letter named “SURVODUTIDE” sold by an online peptide vendor among products that “are unapproved new drugs.” Despite “for research use only” labeling, the agency found that the seller’s website showed the products were intended for human use (FDA warning letter to Xcel Research, December 10, 2024).
- Controlled substances. Survodutide is a peptide, not a steroid, and is not among the anabolic steroids listed in Schedule III (21 CFR 1308.13).
What the research shows
All trials below were funded by Boehringer Ingelheim. Results are mean changes from baseline.
Obesity without diabetes: phase 2 dose finding
A 46-week phase 2 trial at 43 centers in 12 countries randomized 387 adults with a BMI of 27 or higher and no diabetes to survodutide 0.6, 2.4, 3.6 or 4.8 mg or placebo weekly, with a fast 20-week dose escalation (le Roux et al., Lancet Diabetes Endocrinol 2024):
| Arm | Weight change at 46 weeks (95% CI) |
|---|---|
| Placebo | −2.8% (−4.9 to −0.7) |
| 0.6 mg | −6.2% (−8.3 to −4.1) |
| 2.4 mg | −12.5% (−14.5 to −10.5) |
| 3.6 mg | −13.2% (−15.3 to −11.2) |
| 4.8 mg | −14.9% (−16.9 to −13.0) |
Only 60.4% of participants completed the 46 weeks. In people who actually stayed on 4.8 mg, weight fell by 18.7% versus 2.3% on placebo (le Roux et al., Diabetes Obes Metab 2025). About a quarter of participants on survodutide stopped because of adverse events, most of them during the rapid escalation phase. A post hoc analysis reported that systolic blood pressure fell by 8.6 mmHg on 4.8 mg versus 2.5 mmHg on placebo (le Roux et al., Diabetes Obes Metab 2025).
Obesity without diabetes: SYNCHRONIZE-1
SYNCHRONIZE-1 is the pivotal phase 3 obesity trial. It randomized 725 adults (mean BMI 37.9, mean weight 108.8 kg) with a BMI of 30 or higher, or 27 or higher with at least one weight-related condition other than diabetes, to survodutide up to 3.6 mg, up to 6.0 mg or placebo weekly for 76 weeks, alongside lifestyle counseling (le Roux et al., NEJM 2026):
| Outcome at 76 weeks | Placebo | 3.6 mg | 6.0 mg |
|---|---|---|---|
| Weight change (95% CI) | −5.4% (−6.9 to −4.0) | −12.2% (−13.6 to −10.8) | −13.0% (−14.4 to −11.6) |
| Lost ≥5% | 46.3% | 72.6% | 71.9% |
| Gastrointestinal adverse events | 47.9% | 80.9% | 89.7% |
These figures use the “treatment-regimen” estimand, which counts everyone regardless of stopping the drug, switching to other obesity medicines or a prolonged dose escalation. That is one reason the placebo group lost 5.4%. Using the “efficacy” estimand, which assumes people stayed on treatment, Boehringer reported weight loss of up to 16.6% versus 3.2% on placebo (Boehringer Ingelheim press release, April 28, 2026). No deaths were reported.
The 6.0 mg dose gave only slightly more weight loss than 3.6 mg on the treatment-regimen estimand, with more gastrointestinal effects.
Obesity with type 2 diabetes: SYNCHRONIZE-2
SYNCHRONIZE-2 randomized 752 adults with type 2 diabetes and a BMI of 27 or higher (mean age 55.7, mean BMI 36.5, mean HbA1c 7.4%) to survodutide 3.6 mg, 6.0 mg or placebo weekly for 76 weeks (Wharton et al., NEJM 2026):
| Outcome at 76 weeks | Placebo | 3.6 mg | 6.0 mg |
|---|---|---|---|
| Weight change (95% CI) | −3.9% (−4.9 to −2.9) | −8.2% (−9.2 to −7.2) | −9.8% (−10.8 to −8.8) |
| Lost ≥5% | 35.1% | 57.6% | 64.5% |
| HbA1c change (percentage points) | −0.2 | −0.9 | −0.8 |
| Gastrointestinal adverse events | 38.6% | 72.8% | 77.7% |
HbA1c is the average blood sugar over the past 2–3 months. Weight loss was smaller than in SYNCHRONIZE-1, which enrolled people without diabetes.
Type 2 diabetes: phase 2 versus semaglutide
A 16-week phase 2 trial randomized 413 adults with type 2 diabetes on metformin to six survodutide dose groups (up to 2.7 mg once weekly or 1.8 mg twice weekly), placebo, or open-label semaglutide up to 1.0 mg weekly (Blüher et al., Diabetologia 2024):
| Outcome at 16 weeks | Survodutide | Semaglutide up to 1.0 mg |
|---|---|---|
| HbA1c change | −0.91% to −1.71% across dose groups | −1.47% |
| Weight change | Up to −8.7% (1.8 mg twice weekly) | −5.3% |
| Stopped due to adverse events | 15.9% | 4.0% |
The HbA1c fall with low-dose survodutide (0.9 mg weekly) was similar to semaglutide. Doses of 1.8 mg weekly and above produced more weight loss than semaglutide. Placebo-group discontinuation for adverse events was 5.1%. This was a short trial with an unblinded semaglutide arm, and no phase 3 head-to-head trial against semaglutide or tirzepatide has been published.
Fatty liver disease (MASLD and MASH)
Glucagon acts mainly on the liver, so liver disease is a major focus of survodutide’s development.
| Trial | Design | Main results |
|---|---|---|
| Phase 2 MASH (Sanyal et al., NEJM 2024) | 293 adults with biopsy-confirmed MASH and fibrosis stage F1–F3; 2.4, 4.8 or 6.0 mg vs placebo; 48 weeks | MASH improved without worse fibrosis in 47%, 62% and 43% vs 14% on placebo; fibrosis improved by at least one stage in 34%, 36% and 34% vs 22% |
| SYNCHRONIZE-MASLD (Kaplan et al., Nat Med 2026) | 216 adults with obesity and at-risk MASLD in the US and Spain; 6.0 mg vs placebo (2:1); 48 weeks | Liver fat fell by at least 30% in 68.5% vs 28.6% (treatment-regimen) and 84.2% vs 24.3% (efficacy estimand); weight −8.7% vs −1.4% (treatment-regimen) |
MASLD (metabolic dysfunction-associated steatotic liver disease) is the newer name for non-alcoholic fatty liver disease. Liver fat was measured by MRI (MRI-PDFF).
A post hoc analysis of the phase 2 MASH trial in 170 participants with F2–F3 fibrosis estimated that weight loss explained about 67–72% of the improvement in MASH itself, but only about 36% of the improvement in fibrosis (Noureddin et al., Hepatology 2026). The authors suggested a possible direct effect of glucagon receptor activation in the liver. This is a statistical analysis of a phase 2 trial, not proof of a direct effect. Phase 3 trials in MASH with F2–F3 fibrosis and in MASH cirrhosis (the LIVERAGE program) are ongoing.
Body composition and performance
Survodutide is not an anabolic agent. No trial has studied it in lean or resistance-trained people, and the published phase 2 and phase 3 abstracts do not report lean-mass outcomes. As with other weight-loss drugs, part of the weight lost is expected to be lean tissue, but the size of that share has not been reported for survodutide.
Evidence summaries
A 2025 meta-analysis of six randomized trials (1,272 participants) found that survodutide lowered HbA1c by 0.66 percentage points (95% CI 0.23–1.08) and body weight by 6.7 kg (95% CI 3.4–10.0) versus placebo, with larger effects at higher doses and longer treatment (Xiao et al., Diabetes Obes Metab 2025). It found a higher risk of stopping treatment because of adverse events, mainly gastrointestinal, but no significant increase in serious adverse events. A 2026 class-wide meta-analysis of 19 trials of glucagon/GLP-1 dual agonists found that mazdutide and survodutide showed the largest weight effects in the class (Amjad et al., Diabetes Obes Metab 2026).
Side effects and risks
Survodutide has no label. This section relies on published trial data from trials lasting up to 76 weeks. No cardiovascular outcomes trial has reported yet.
Gastrointestinal effects
Nausea, vomiting, diarrhea and constipation are the most common adverse events. They are dose-related and cluster in the dose-escalation period. In SYNCHRONIZE-MASLD (Kaplan et al., Nat Med 2026):
| Adverse event | Placebo (n = 70) | Survodutide 6.0 mg (n = 146) |
|---|---|---|
| Nausea | 14.3% | 56.2% |
| Vomiting | 7.1% | 42.5% |
| Diarrhea | 10.0% | 29.5% |
| Constipation | 10.0% | 28.1% |
| Stopped due to adverse events | 10.0% | 23.3% |
| Serious adverse events | 11.4% | 9.6% |
In the phase 2 MASH trial, nausea (66% vs 23%), diarrhea (49% vs 23%) and vomiting (41% vs 4%) were more frequent than on placebo, while serious adverse events were similar (8% vs 7%) (Sanyal et al., NEJM 2024). Early trials used fast dose escalation, and the investigators suggested slower escalation could reduce these effects (Blüher et al., Diabetologia 2024).
Heart rate and cardiovascular effects
Glucagon stimulates the heart, so heart rate has been watched closely.
- In the phase 2 diabetes trial, heart rate rose by 2.3–7.3 beats per minute across survodutide groups at 16 weeks, versus 5.9 on semaglutide and 1.67 on placebo (Blüher et al., Diabetologia 2024).
- In SYNCHRONIZE-MASLD, heart rate at week 52 rose by 3.6 beats per minute versus 0.8 on placebo, and no participant had a dangerous lengthening of the QT interval on ECG (Kaplan et al., Nat Med 2026).
- In an early phase 1b study with rapid escalation over 6 weeks, 7.5% of participants stopped the drug because of a cardiac or vascular adverse event (Jungnik et al., Diabetes Obes Metab 2023).
SYNCHRONIZE-CVOT, an event-driven trial targeting 4,935 adults with a BMI of 27 or higher and established cardiovascular disease, chronic kidney disease or at least two weight-related complications or cardiovascular risk factors, is testing whether survodutide is safe for the heart, using a composite of five major cardiovascular events as its primary endpoint (Kosiborod et al., JACC Heart Fail 2024).
Gallbladder, pancreas and thyroid
In SYNCHRONIZE-MASLD, one participant on survodutide had gallstones with gallbladder inflammation. There were no confirmed cases of acute pancreatitis, drug-induced liver injury, pancreatic cancer or thyroid cancer on survodutide (Kaplan et al., Nat Med 2026). Trials of this size and length cannot rule out rare risks seen with other GLP-1-based drugs.
Who it has not been studied in
Trials enrolled adults with overweight, obesity, type 2 diabetes or fatty liver disease. No controlled trial has tested survodutide in athletes or trained lifters, in pregnancy, in adolescents, or in people with type 1 diabetes.
Unregulated “research” products
Outside clinical trials, survodutide cannot be prescribed anywhere. The FDA considers online “research use only” survodutide an unapproved new drug (FDA warning letter to Xcel Research, December 10, 2024). No published lab study has tested the content, purity or sterility of such products, so their identity and dose are unverified.
Use in sport
Survodutide is not named on the WADA Prohibited List. However, the S0 class bans “any pharmacological substance” not covered elsewhere on the List that has no current approval by any government health authority, explicitly including drugs “under pre-clinical or clinical development” (WADA 2026 Prohibited List). As an unapproved investigational drug, survodutide falls into that class and is prohibited at all times. Its status could change if a regulator approves it.
Key takeaways
- A glucagon and GLP-1 dual agonist. Survodutide is a long-acting, glucagon-based peptide in the same class as mazdutide, developed by Zealand Pharma and Boehringer Ingelheim.
- Not approved anywhere. It holds FDA Fast Track and Breakthrough Therapy designations for MASH, but no regulator has approved it for any use.
- Weight loss in phase 3. In SYNCHRONIZE-1, weight fell by 12.2–13.0% at 76 weeks versus 5.4% on placebo (treatment-regimen estimand); in people with type 2 diabetes the fall was 8.2–9.8% versus 3.9%.
- Liver results stand out. In phase 2 MASH, up to 62% improved versus 14% on placebo, and fibrosis improvement appeared to depend less on weight loss than MASH improvement did.
- Gastrointestinal effects and dropouts are common. Up to about 90% had gastrointestinal events at 6.0 mg, and about a quarter stopped treatment for adverse events in some trials. Heart rate rises modestly, and the cardiovascular outcomes trial is still running.
- Gray-market products are unverified. The FDA treats online “research” survodutide as an unapproved drug, and WADA’s S0 class prohibits it in sport.
Sources
- Zimmermann T, Thomas L, Baader-Pagler 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. PubMed.
- Jungnik A, Arrubla Martinez J, Plum-Mörschel L, 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. PubMed.
- Yazawa R, Ishida M, Balavarca Y, 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. PubMed.
- Lawitz EJ, Fraessdorf M, Neff GW, 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. PubMed.
- le Roux CW, Steen O, Lucas KJ, 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. PubMed.
- le Roux CW, Steen O, Lucas KJ, et al. Subgroup analysis by sex and baseline BMI in people with a BMI ≥27 kg/m2 in the phase 2 trial of survodutide, a glucagon/GLP-1 receptor dual agonist. Diabetes Obes Metab. 2025;27(4):1773–1782. PubMed.
- le Roux CW, Steen O, Lucas KJ, et al. Survodutide, a glucagon receptor/glucagon-like peptide-1 receptor dual agonist, improves blood pressure in adults with obesity: a post hoc analysis from a randomized, placebo-controlled, dose-finding, phase 2 trial. Diabetes Obes Metab. 2025;27(2):993–996. PubMed.
- le Roux CW, Wharton S, Startseva E, et al. Survodutide once weekly for the treatment of adults with obesity. N Engl J Med. 2026;395(8):776–787. PubMed.
- Wharton S, le Roux CW, Startseva E, et al. Survodutide once weekly in adults with obesity and type 2 diabetes. N Engl J Med. Published online October 1, 2026. doi:10.1056/NEJMoa2607219. PubMed.
- Blüher M, Rosenstock J, Hoefler J, et al. Dose-response effects on HbA1c 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. PubMed.
- Sanyal AJ, Bedossa P, Fraessdorf M, et al. A phase 2 randomized trial of survodutide in MASH and fibrosis. N Engl J Med. 2024;391(4):311–319. PubMed.
- Kaplan LM, Startseva E, le Roux CW, 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. PubMed.
- Noureddin M, Sanyal AJ, Bedossa P, et al. Weight reduction-dependent/-independent effects of survodutide on liver endpoints: mediation analysis of a phase 2 trial in MASH. Hepatology. Published online August 3, 2026. doi:10.1097/HEP.0000000000001825. PubMed.
- Kosiborod MN, Platz E, Wharton S, et al. Survodutide for the treatment of obesity: rationale and design of the SYNCHRONIZE cardiovascular outcomes trial. JACC Heart Fail. 2024;12(12):2101–2109. PubMed.
- Xiao YJ, Yu S, Zhang YL, et al. Efficacy and safety of survodutide on glycemic control and weight loss in adults: a systematic review and meta-analysis. Diabetes Obes Metab. 2025;27(12):7062–7074. PubMed.
- Amjad MM, Khan MM, Sarwar F, et al. Efficacy and safety of dual GLP-1/glucagon receptor agonism in overweight and obesity: a class-specific systematic review and meta-analysis. Diabetes Obes Metab. Published online September 29, 2026. doi:10.1111/dom.71400. PubMed.
- Boehringer Ingelheim. Boehringer receives U.S. FDA Breakthrough Therapy designation and initiates two phase III trials in MASH for survodutide. Press release, October 8, 2024. BioSpace.
- Boehringer Ingelheim. Boehringer Ingelheim’s novel glucagon/GLP-1 dual agonist survodutide achieved significant weight loss of 16.6% delivering meaningful metabolic improvement in people with obesity or overweight in Phase III trial. Press release, April 28, 2026. PharmaShots Newswire.
- National Center for Biotechnology Information. Survodutide, PubChem CID 171378821. PubChem.
- US Food and Drug Administration. Warning letter to Xcel Research LLC, MARCS-CMS 694608, December 10, 2024. FDA.
- Code of Federal Regulations. 21 CFR 1308.13, Schedule III. eCFR.
- World Anti-Doping Agency. World Anti-Doping Code International Standard: Prohibited List 2026. WADA 2026 Prohibited List.