Survodutide

Survodutide is a lab-made peptide best known for weight loss and, increasingly, for liver disease (MASH/NASH) — it activates both the GLP-1 and glucagon receptors at once (a 'dual agonist'), and the glucagon component is thought to add effects on energy expenditure and liver fat beyond GLP-1 alone. Given as a once-weekly injection, it is investigational and not FDA-approved.

Survodutide (a GLP-1/glucagon dual agonist) has been studied for obesity and fatty-liver disease. In the Phase 3 SYNCHRONIZE-1 obesity trial (2026), adults on once-weekly survodutide for 76 weeks had greater average weight reduction than placebo, and a Phase 3 trial in obesity with fatty-liver disease reported reductions in liver fat and body weight; an earlier Phase 2 trial in MASH with fibrosis reported improved liver histology. Reported trial side effects include gastrointestinal symptoms and increased heart rate. These are trial results in studied populations, not expected outcomes, and specifics will shift as the remaining Phase 3 trials report. The research attributes this weight reduction largely to reduced appetite and food intake (greater satiety via the gut-hormone pathway these agents act on), an appetite and energy-intake mechanism measured across the trials.

⚠️ investigational — not FDA-approved. Survodutide (BI 456906, Boehringer Ingelheim / Zealand Pharma). Phase 3 has now read out in two indications — the pivotal obesity trial SYNCHRONIZE-1 published in the New England Journal of Medicine (2026), in which participants on survodutide had up to ~16.6% mean weight reduction vs ~3.2% on placebo at 76 weeks (efficacy estimand), and the obesity + MASLD trial SYNCHRONIZE-MASLD published in Nature Medicine (2026). Genuinely still ongoing — the Phase 3 MASH-histology trials (LIVERAGE and LIVERAGE-Cirrhosis) and the cardiovascular outcomes trial, none of which have reported. FDA granted Breakthrough Therapy designation for non-cirrhotic MASH with moderate/advanced fibrosis in September 2024 — a designation that speeds review, not an approval; no NDA/BLA is on record. Once-weekly SubQ. Not DEA-scheduled. Survodutide is not named on the WADA 2026 Prohibited List, and no GLP-1 or glucagon term appears anywhere on it — but it has no marketing approval from any regulatory authority anywhere, and S0 (Non-Approved Substances) prohibits at all times "any pharmacological substance... with no current approval by any governmental regulatory health authority for human therapeutic use (e.g. drugs under pre-clinical or clinical development...)". S0 therefore captures survodutide by default: it is off-limits in drug-tested sport. This is the opposite of the approved GLP-1 drugs (semaglutide, liraglutide, tirzepatide), whose approval is precisely what takes them out of S0's reach — the family pattern does not transfer to an investigational member. Verified against the local archive `docs/legal/wada-2026-prohibited-list.txt` (S0 clause + full-text term search) on 2026-09-07. Re-verify when the 2027 Prohibited List publishes ~September–October 2026. Values below will shift as the remaining Phase 3 data and any regulatory filings report — re-verify before relying on specifics.

Survodutide is investigational and not FDA-approved; research-supply purity and identity are not guaranteed. It is not on the WADA Prohibited List. VialWise is a research and educational reference, not medical advice — consult a licensed professional.

⚠️ For research and educational purposes only. Survodutide is an unapproved investigational drug. Information in this entry is informational, not medical advice. Always confirm dose calculations with the in-app calculator and consult appropriate professional guidance before any protocol decisions.

⚠️ Investigational — specifics will change. Survodutide is in active Phase 3 development. The obesity and obesity + MASLD Phase 3 trials have now published, but the MASH-histology Phase 3 trials and the cardiovascular outcomes trial have not reported, and there is no FDA approval. Doses, half-life, efficacy, and safety figures here are from published trials and will be refined (or the compound approved/abandoned) as data matures. Treat every number here as a current-best-evidence snapshot, not a settled fact.

⚠️ Glucagon-receptor agonism adds mechanisms — and risks — beyond pure GLP-1. The glucagon arm can raise heart rate and affect hepatic glucose output. This is not just "a stronger GLP-1." Dual agonists have their own emerging safety profile distinct from semaglutide/tirzepatide.

Survodutide (BI 456906) is a GLP-1 receptor / glucagon receptor dual agonist — the next receptor-coverage step beyond the pure GLP-1 agonists, adding glucagon-receptor activity to GLP-1's appetite-suppression and glycemic effects. The glucagon arm is thought to add energy expenditure and hepatic-fat reduction, which is also why survodutide has drawn interest for MASH/NASH.[⁴][⁵] It is investigational and once-weekly.

Development — Phase 2 foundations. Boehringer Ingelheim / Zealand Pharma. The Phase 2 obesity dose-finding trial (le Roux et al., Lancet Diabetes Endocrinology 2024) reported weight loss across escalating doses;[¹] a T2D dose-response trial (Blüher, Rosenstock et al., Diabetologia 2024) supported glycemic efficacy.[²] These established the dose range that Phase 3 carried forward.

Phase 3 — obesity (SYNCHRONIZE-1, published). In a 76-week Phase 3 trial of 725 adults with obesity and without diabetes, participants were randomized to once-weekly survodutide, or placebo. As reported in the New England Journal of Medicine (2026), mean weight change on the treatment-regimen estimand was −12.2% and −13.0% vs −5.4% on placebo, with ≥5% weight reduction in 72.6% / 71.9% vs 46.3% of participants (P<0.001 for all comparisons); on the efficacy estimand the sponsor reported up to ~16.6% vs ~3.2% on placebo. Gastrointestinal adverse events — mostly mild to moderate — occurred in 80.9% / 89.7% of the survodutide groups vs 47.9% on placebo; no deaths were reported.[³] *These are trial results in a studied population, not an expected outcome for any individual.*

Phase 3 — obesity + liver disease (SYNCHRONIZE-MASLD, published). In a 48-week Phase 3 trial of 216 adults with obesity and at-risk MASLD randomized 2:1 to survodutide or placebo, both co-primary endpoints were met: ≥30% reduction in MRI-PDFF liver fat in 84.2% vs 24.3% (efficacy estimand; 68.5% vs 28.6% on the treatment-regimen estimand) and mean weight change of −12.2% vs −1.0% (Nature Medicine, 2026).[⁴]

Phase 2 — MASH histology. An earlier 48-week Phase 2 trial in 293 adults with biopsy-confirmed MASH and F1–F3 fibrosis (survodutide vs placebo) reported MASH improvement without worsening of fibrosis in 47% / 62% / 43% vs 14% on placebo, and ≥1-stage fibrosis improvement in 34% / 36% / 34% vs 22% (New England Journal of Medicine, 2024).[⁵] This trial is the evidentiary basis for survodutide's MASH development program and for its FDA Breakthrough Therapy designation.

What is genuinely still ongoing. The two Phase 3 MASH-histology trials — LIVERAGE in non-cirrhotic mash f2–F3 ([NCT06632444](https://clinicaltrials.gov/study/NCT06632444), n≈1,800) and LIVERAGE-Cirrhosis ([NCT06632457](https://clinicaltrials.gov/study/NCT06632457), n≈1,590) — are recruiting and have not reported. The Phase 3 cardiovascular outcomes trial ([NCT06077864](https://clinicaltrials.gov/study/NCT06077864), n≈5,531) has reached primary completion but has published only baseline characteristics so far.[⁶] The Phase 3 obesity + T2D trial (SYNCHRONIZE-2, [NCT06066528](https://clinicaltrials.gov/study/NCT06066528)) is complete with publication pending.

Where it sits in the library's GLP-1 family. Pure GLP-1: semaglutide, liraglutide, dulaglutide, exenatide. GLP-1/GIP: tirzepatide. GLP-1/glucagon dual: survodutide (this entry) and [mazdutide.md](./mazdutide.md). GLP-1/GIP/glucagon triple: retatrutide. Adding receptor arms is the broad arc of the field; survodutide is one of the two GLP-1/glucagon dual-agonist rungs.

Regulatory status. Investigational; not FDA-approved, with no NDA/BLA on record. The FDA granted survodutide Breakthrough Therapy designation in September 2024 for non-cirrhotic MASH with moderate to advanced fibrosis — a designation expedites development and review; it is not an approval and says nothing about whether the compound will ultimately be approved. The EMA accepted survodutide into its PRIME scheme (November 2023) and China's NMPA granted Breakthrough Therapy designation (June 2024). Not DEA-scheduled. Survodutide is not named on the WADA 2026 Prohibited List, and no GLP-1 or glucagon term appears anywhere on it — but it has no marketing approval from any regulatory authority anywhere, and S0 (Non-Approved Substances) prohibits at all times "any pharmacological substance... with no current approval by any governmental regulatory health authority for human therapeutic use (e.g. drugs under pre-clinical or clinical development...)". S0 therefore captures survodutide by default: it is off-limits in drug-tested sport. This is the opposite of the approved GLP-1 drugs (semaglutide, liraglutide, tirzepatide), whose approval is precisely what takes them out of S0's reach — the family pattern does not transfer to an investigational member. Verified against the local archive `docs/legal/wada-2026-prohibited-list.txt` (S0 clause + full-text term search) on 2026-09-07. Re-verify when the 2027 Prohibited List publishes ~September–October 2026.

Commonly reported

• GI: nausea, vomiting, diarrhea, decreased appetite (dose/titration-dependent — the class hallmark). In Phase 3 SYNCHRONIZE-1 these were the dominant adverse events, mostly mild to moderate and concentrated during dose escalation, occurring in 80.9% and 89.7% of participants vs 47.9% on placebo.[³]
• Increased heart rate (the glucagon arm + GLP-1 class both contribute — notable for dual agonists)
• Injection-site reactions, fatigue, headache

Serious

• Acute pancreatitis (severe abdominal pain radiating to back) — GLP-1-class concern
• Gallbladder disease
• Sustained tachycardia / palpitations (watch given the glucagon-arm HR effect)
• Severe persistent GI symptoms → dehydration → acute kidney injury
• Medullary thyroid carcinoma signal is a GLP-1-class boxed-warning concern; dual-agonist long-term data are immature

Personal/family history of medullary thyroid carcinoma or MEN2 — GLP-1-class concern; carry the same caution pending dual-agonist-specific data.

History of pancreatitis — caution.

Cardiovascular caution — the glucagon arm's heart-rate effect warrants attention.

Other incretin agonists — do not co-administer.

Pregnancy/lactation — no adequate data; avoid.

Investigational status — unapproved; research-supply purity/identity not guaranteed.

Regulatory: not FDA-approved (an FDA Breakthrough Therapy designation for MASH exists, but a designation is not an approval); not DEA-scheduled; not named on the WADA 2026 Prohibited List, but S0 captures it by default because it holds no approval anywhere — off-limits in drug-tested sport. Re-verify when the 2027 list publishes ~September–October 2026.

GLP-1 receptor agonist

A compound that switches on the GLP-1 receptor, the same target a natural gut hormone uses to signal fullness and help regulate blood sugar.

Glucagon receptor

A receptor that, when activated, affects blood-sugar output by the liver and may increase energy expenditure.

Dual agonist

A compound that activates two different receptors at once (for example, the GLP-1 and glucagon receptors).

Investigational

Still being studied and not yet approved by regulators for general use.

Subcutaneous

An injection into the fatty layer just under the skin, rather than into a muscle or vein.

1. le Roux CW, et al. (2024). Glucagon and GLP-1 receptor dual agonist survodutide for obesity: a randomised, double-blind, placebo-controlled, dose-finding phase 2 trial. Lancet Diabetes Endocrinol, 12(3):162–173.(PMID 38330987 · NCT04667377)
2. Blüher M, Rosenstock J, et al. (2024). 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, 67(3):470–482.(PMID 38095657 · NCT04153929)
3. le Roux CW, Wharton S, et al. (2026). Survodutide Once Weekly for the Treatment of Adults with Obesity. N Engl J Med, 2026 Jun 7.(PMID 42253238 · NCT06066515)
4. Kaplan LM, Startseva E, le Roux CW, et al. (2026). 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 Jun 7.(PMID 42252333 · NCT06309992)
5. Sanyal AJ, Bedossa P, et al. (2024). A Phase 2 Randomized Trial of Survodutide in MASH and Fibrosis. N Engl J Med, 391(4):311–319.(PMID 38847460 · NCT04771273)
6. Platz E, et al. (2025). Baseline Characteristics of the SYNCHRONIZE Cardiovascular Outcomes Trial. JACC Heart Fail, 14(5):102780.(PMID 41329105 · NCT06077864)

• Amycretin — same mechanism class
• CagriSema — same mechanism class
• Dulaglutide — same mechanism class
• Exenatide — same mechanism class
• Liraglutide — same mechanism class
• Mazdutide — same mechanism class