Survodutide: The Liver-Focused Dual Agonist
Boehringer Ingelheim's once-weekly GLP-1 / glucagon receptor dual agonist (formerly BI 456906), now in phase 3 trials.
How It Works
Activates both the GLP-1 receptor (appetite suppression, insulin secretion) and the glucagon receptor (proposed to raise energy expenditure and act on hepatic metabolism). The glucagon arm is what differentiates it from semaglutide.
Glucagon signaling is a proposed mechanism for raising energy expenditure, which may add to the weight loss driven by GLP-1 appetite suppression.
Glucagon receptor signaling in the liver is thought to promote hepatic fat mobilization, which is why survodutide is being studied in MASH.
Survodutide contains a C18 diacid that binds albumin, prolonging its half-life to enable once-weekly subcutaneous dosing (survodutide perspectives review, PMID: 37330144). Phase 3 SYNCHRONIZE trials use weekly subcutaneous dosing with a slow titration to manage GI tolerability.
What the Data Shows
Once-Weekly Doses Studied in Phase 3 Trials
Survodutide is investigational and not approved. The doses below describe what the trials studied — they are not a protocol for personal use.
Key Takeaways
- Phase 2 produced up to 19% mean weight loss at 46 weeks (4.8 mg, as reported in a 2026 review); by the dose-finding trial’s primary planned-treatment analysis the 4.8 mg dose gave −14.9% vs −2.8% on placebo (PMID: 38330987). The phase 3 trials, scored with the stricter treatment-regimen estimand over 76 weeks, came in lower.
- Phase 3 SYNCHRONIZE-1 (obesity without diabetes, n=725; PMID: 42253238) reported mean weight change of −12.2% (3.6 mg) and −13.0% (6.0 mg) vs −5.4% on placebo at 76 weeks (treatment-regimen estimand).
- Phase 3 SYNCHRONIZE-2 (obesity with type 2 diabetes, n=752; PMID: 42820639) reported −8.2% (3.6 mg) and −9.8% (6.0 mg) vs −3.9% on placebo at 76 weeks, with HbA1c falling 0.9 and 0.8 percentage points vs 0.2 on placebo from a 7.4% baseline.
- Two placebo-controlled phase 3 liver trials run separately from the obesity program: LIVERAGE (NCT06632444, MASH with F2–F3 fibrosis) and LIVERAGE-Cirrhosis (NCT06632457, compensated MASH cirrhosis). Both are listed as recruiting on ClinicalTrials.gov.
- Glucagon agonism is the proposed differentiator: higher energy expenditure is described as a proposed mechanism, not an established advantage over pure GLP-1 drugs (PMID: 42822760).
- Comparative effectiveness, durability, long-term safety, treatment persistence and effects after stopping — a 2026 review in Contemporary Clinical Trials lists these as still to be established (PMID: 42822760).
- Whether glucagon-mediated effects on glycemic control stay net beneficial in T2D beyond 76 weeks (SYNCHRONIZE-2 showed HbA1c improving over that period).
- Head-to-head vs retatrutide (also a glucagon-containing molecule).
- Cardiovascular outcomes — the phase 3 cardiovascular safety trial, SYNCHRONIZE-CVOT (design paper: PMID: 39453356; registry: NCT06077864), is listed on ClinicalTrials.gov as completed in June 2026 but has not yet published results.
- Long-term hepatic safety — the phase 2 biopsy trial in MASH ran 48 weeks (PMID: 38847460).
- Whether survodutide will be approved for MASH, for obesity, or both, and in what order.
Frequently Asked Questions
What is survodutide?
Survodutide (formerly BI 456906) is a 29-amino-acid peptide derived from glucagon (PMID: 37330144), developed by Boehringer Ingelheim. It is a dual agonist at the GLP-1 receptor (like semaglutide) and the glucagon receptor, whose activity is proposed to raise energy expenditure (PMID: 42822760). It is in phase 3 trials for both obesity and MASH (metabolic dysfunction-associated steatohepatitis).
How does survodutide differ from semaglutide and tirzepatide?
Semaglutide is a pure GLP-1 agonist. Tirzepatide is a GLP-1/GIP dual agonist. Survodutide is a GLP-1/glucagon dual agonist. Its glucagon receptor activity is a proposed mechanism for raising energy expenditure and acting on hepatic metabolism (PMID: 42822760) — one reason it is also being studied in MASH alongside obesity.
Is survodutide FDA-approved?
Not yet. As of October 2026 it remains investigational. Boehringer Ingelheim announced on October 8, 2024 that the FDA had granted survodutide Breakthrough Therapy designation for adults with non-cirrhotic MASH and moderate or advanced fibrosis (company press release); the designation is not an approval. Phase 3 obesity results are now published: SYNCHRONIZE-1 (adults without diabetes) and SYNCHRONIZE-2 (adults with type 2 diabetes) both appeared in the New England Journal of Medicine in 2026. The LIVERAGE MASH phase 3 trial (NCT06632444) is listed as recruiting on ClinicalTrials.gov. Its Part 1 primary endpoints (MASH resolution without worsening of fibrosis, and at least a 1-point improvement in fibrosis stage with no worsening of MASH) are assessed at week 52, and its estimated primary completion date is December 2031.
How does survodutide compare to retatrutide?
Both contain a glucagon component. Retatrutide is a triple agonist (GLP-1 + GIP + glucagon); survodutide is a dual agonist (GLP-1 + glucagon, no GIP). Survodutide produced up to ~19% weight loss at 46 weeks in Phase 2 (4.8 mg, as reported in a 2026 review; −14.9% in the primary planned-treatment analysis). Survodutide also has phase 2 biopsy data in MASH: at 48 weeks, MASH improved without worsening of fibrosis in 43–62% of participants across doses vs 14% on placebo (PMID: 38847460).
What is MASH and why does survodutide target it?
MASH (metabolic dysfunction-associated steatohepatitis, formerly NASH) is fatty liver disease with inflammation and fibrosis. Survodutide's glucagon receptor activity is proposed to act on hepatic metabolism (PMID: 42822760), and in a 48-week phase 2 trial in biopsy-confirmed MASH it was superior to placebo for MASH improvement without worsening of fibrosis (PMID: 38847460). Semaglutide (Wegovy) now carries an FDA accelerated approval for noncirrhotic MASH with moderate-to-advanced (F2–F3) fibrosis; survodutide is not approved for MASH.
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