Survodutide phase 3: what the SYNCHRONIZE trials have reported
Prepared by: Research Desk. Sources are linked for verification.
Published 26 October 2026
At a glance
- What it is: survodutide (BI 456906) is an investigational peptide that activates both the glucagon receptor and the GLP-1 receptor, developed by Boehringer Ingelheim
- Phase 3 programme: the SYNCHRONIZE trials, which compare survodutide with placebo in adults with obesity, with or without type 2 diabetes or liver disease
- Published so far: SYNCHRONIZE-1 (August 2026) and SYNCHRONIZE-2 (October 2026) in the New England Journal of Medicine, and SYNCHRONIZE-MASLD in Nature Medicine (August 2026)
- Still running: a cardiovascular outcomes trial and regional trials in China and Japan, whose design papers are published but whose results are not
- Status: survodutide remains investigational in this record; no regulatory approval has been reported
Why a dual agonist
GLP-1 receptor agonists reduce food intake. Glucagon receptor activation is studied for a different reason: in animal work it raises energy expenditure and acts strongly on the liver. Survodutide combines both activities in one molecule.
A 2026 mouse study in Molecular Metabolism (Zimmermann et al., 2026), funded by the developer, used a fluorescently labelled form of survodutide to map where it acts in the brain. The labelled peptide reached circumventricular organs, brain regions with a leaky blood–brain barrier, and nearby hypothalamic and hindbrain nuclei, without evidence of crossing the barrier uniformly. The glucagon receptor was barely detectable in two of these regions, while the GLP-1 receptor was present, which the authors read as support for the intake-reducing effect being GLP-1 receptor-driven.
Phase 2: the starting point
- Obesity: a 46-week phase 2 trial in 387 adults without diabetes (le Roux et al., 2024, The Lancet Diabetes & Endocrinology; NCT04667377) reported mean body-weight changes from about −6% to −15% across the survodutide arms, versus −2.8% with placebo. Gastrointestinal adverse events were reported in 75% of survodutide recipients and 42% of placebo recipients
- Liver disease: a 48-week trial in 293 adults with biopsy-confirmed metabolic dysfunction-associated steatohepatitis (MASH) and fibrosis (Sanyal et al., 2024, NEJM; NCT04771273) reported histological improvement in MASH without worsening of fibrosis in 43% to 62% of the survodutide groups versus 14% with placebo
SYNCHRONIZE-1: adults with obesity, without diabetes
le Roux et al. (2026) reported a 76-week, double-blind trial (NCT06066515) in 725 adults with a body-mass index of at least 30, or at least 27 with an obesity-related complication other than diabetes. Participants were randomly assigned 1:1:1 to one of two survodutide strengths or placebo, alongside lifestyle counselling.
- Primary result: mean change in body weight at week 76 was −12.2% and −13.0% in the two survodutide groups and −5.4% with placebo (treatment-regimen estimand)
- Second primary end point: 72.6% and 71.9% of the survodutide groups reached at least 5% weight reduction, versus 46.3% with placebo
- Adverse events: gastrointestinal events, mostly mild to moderate, were reported in 80.9% and 89.7% of the survodutide groups and 47.9% of the placebo group; no deaths were reported
- Funding: Boehringer Ingelheim
SYNCHRONIZE-2: adults with obesity and type 2 diabetes
Wharton et al. (2026), published online on 1 October 2026 alongside a presentation at the EASD annual meeting, reported the companion trial (NCT06066528) in 752 adults with type 2 diabetes and a body-mass index of at least 27.
- Primary result: mean weight change at week 76 was −8.2% and −9.8% in the two survodutide groups and −3.9% with placebo (treatment-regimen estimand)
- Second primary end point: 57.6% and 64.5% of the survodutide groups reached at least 5% weight reduction, versus 35.1% with placebo
- Glycaemic measure: from a baseline glycated haemoglobin of 7.4%, the mean change was −0.9 and −0.8 percentage points with survodutide and −0.2 with placebo
- Adverse events: gastrointestinal events were reported in 72.8% and 77.7% of the survodutide groups and 38.6% of the placebo group
The developer's press release headlines a larger figure, up to 13.1%, because it uses the efficacy estimand, which assumes participants stayed on the assigned regimen. The NEJM abstract leads with the treatment-regimen estimand, which counts everyone as randomised. The two figures answer different questions and should not be mixed when comparing trials.
SYNCHRONIZE-MASLD: liver fat and body weight
Kaplan et al. (2026), in Nature Medicine, reported a 48-week trial (NCT06309992) in 216 adults with obesity and at-risk metabolic dysfunction-associated steatotic liver disease (MASLD), randomised 2:1 to survodutide or placebo at sites in the United States and Spain.
- Liver fat: using the treatment-regimen estimand, 68.5% of the survodutide group and 28.6% of the placebo group had a reduction of at least 30% in liver fat measured by MRI proton density fat fraction (84.2% versus 24.3% with the efficacy estimand)
- Body weight: mean change was −8.7% with survodutide and −1.4% with placebo (treatment-regimen estimand)
- Correction: the journal published an author correction to the paper in 2026; readers comparing figures should use the corrected version
- Limits named by the authors: the short 48-week duration and recruitment in only two countries
What is still running
- Cardiovascular outcomes: the design of the SYNCHRONIZE cardiovascular outcomes trial was published in 2024 (Kosiborod et al.) and its baseline characteristics in JACC: Heart Failure in 2026 (Platz et al.); outcome results have not been published
- China: SYNCHRONIZE-CN (NCT06214741) enrolled 306 adults; design and baseline data appeared in Diabetes Therapy (Ji et al., 2026)
- Japan: SYNCHRONIZE-JP (NCT06176365) enrolled 274 adults; design and baseline data appeared in Diabetes, Obesity and Metabolism (Yokote et al., 2026)
Limitations of the evidence
- Sponsor involvement: all of the trials above were funded by Boehringer Ingelheim, and company employees are among the authors
- No outcomes data yet: weight, glycaemic and liver-fat changes are surrogate measures; the cardiovascular outcomes trial has not reported
- Estimands differ: headline figures vary depending on whether the treatment-regimen or efficacy estimand is used
- Tolerability: gastrointestinal adverse events were common in every survodutide group
- Trial populations: SYNCHRONIZE-MASLD recruited in two countries only, and regional trials have not yet reported results
Key terms
- Dual agonist: a single molecule that activates two different receptors, here the glucagon and GLP-1 receptors
- Estimand: a precise definition of what a trial result measures, including how events such as stopping the study drug are handled
- MASLD and MASH: metabolic dysfunction-associated steatotic liver disease, and its inflammatory form, steatohepatitis
- MRI-PDFF: an MRI method that estimates the fraction of liver tissue that is fat
Supplier
Purita is a store that sells peptides for laboratory research use only. It does not list survodutide, which is an investigational pharmaceutical product; the link below goes to the store's homepage.
Affiliate disclosure: this is a paid link. KlowSignal earns a commission if a purchase is made through it, at no extra cost to the buyer. A listing is not an endorsement or a statement about product quality. See the affiliate disclosure.
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