Survodutide (development code BI 456906) is an investigational dual agonist from Boehringer Ingelheim and Zealand Pharma. It has completed phase 3 trials in obesity but holds no marketing authorisation in any jurisdiction. This page describes what its trials measured.
Overview
Survodutide's two documented benefit areas are body-weight reduction and improvement in metabolic liver disease. In its phase 3 obesity trial it produced a mean weight change of −13.0% at 76 weeks against −5.4% on placebo; in phase 2 in biopsy-confirmed MASH, it resolved the disease in up to 62% of patients against 14% on placebo. Both are trial results, not approved uses.
What sets survodutide apart within its class is that the liver work is not an afterthought. Most incretin programmes measure hepatic endpoints as secondary outcomes; survodutide has been run with them as the primary question in dedicated trials, which is why its evidence base looks different from mazdutide's or tirzepatide's.
Weight loss, from phase 2 to phase 3
The dose-finding phase 2 trial enrolled 386 adults with a BMI of 27 or higher and no diabetes across 43 centres in 12 countries, testing 0.6, 2.4, 3.6, and 4.8 mg weekly against placebo for 46 weeks. Mean weight change was −6.2%, −12.5%, −13.2%, and −14.9% respectively, versus −2.8% on placebo — a clean dose-response (Lancet Diabetes Endocrinol 2024; PMID 38330987).
SYNCHRONIZE-1, the phase 3 trial, randomised 725 adults with obesity and without diabetes to 3.6 mg, 6.0 mg, or placebo for 76 weeks. Mean weight change was −12.2% and −13.0% against −5.4% on placebo, with 72.6%, 71.9%, and 46.3% respectively losing at least 5% (NEJM 2026; PMID 42253238).
Two details are worth noting. The 6.0 mg dose added almost nothing over 3.6 mg — a plateau, not a ladder. And the placebo group lost 5.4%, a large placebo response that shrinks the between-group difference relative to what the raw percentage suggests.
The liver programme
In phase 2 for MASH (metabolic dysfunction-associated steatohepatitis, formerly NASH), 293 patients with biopsy-confirmed disease received 2.4, 4.8, or 6.0 mg weekly or placebo for 48 weeks. MASH improvement without worsening of fibrosis occurred in 47%, 62%, and 43% of patients versus 14% on placebo. Fibrosis improvement of at least one stage occurred in 34% to 36% versus 22% on placebo — a much narrower margin than the MASH figures (NEJM 2024; PMID 38847460).
SYNCHRONIZE-MASLD, a phase 3 trial in 216 adults with obesity and at-risk steatotic liver disease, tested 6.0 mg against placebo for 48 weeks. Using the efficacy estimand, 84.2% of treated patients versus 24.3% on placebo achieved at least a 30% reduction in MRI-measured liver fat, alongside −12.2% versus −1.0% body weight (Nature Medicine 2026; PMID 42252333). The authors flag the trial's short duration and recruitment limited to the United States and Spain.
Why glucagon is the interesting half
GLP-1 agonism reduces what goes in. Glucagon receptor agonism is hypothesised to increase what goes out — raising energy expenditure and driving fat out of the liver directly, since hepatocytes are where glucagon receptors are most densely expressed.
That hepatic targeting is the mechanistic argument for why a glucagon-containing agonist might do more for fatty liver disease than an appetite-suppressing agent that improves the liver mainly by way of weight loss. Whether the liver effect is genuinely independent of weight loss is an open and actively studied question rather than a settled one.
How survodutide compares
- Mazdutide — the other GLP-1/glucagon dual agonist with phase 3 data, approved in China only, with trials conducted exclusively in Chinese populations.
- Tirzepatide — GLP-1 paired with GIP rather than glucagon; approved, with its own MASH programme.
- Semaglutide — single GLP-1 agonist, the reference point for both weight and liver comparisons.
Survodutide has not been compared head-to-head against any of them. Its distinguishing feature is the depth of its dedicated liver programme, not a demonstrated advantage over alternatives.
Evidence and caveats
- No regulatory approval anywhere; completing phase 3 is not the same as being licensed.
- Only 60.4% of participants completed the 46-week phase 2 treatment period, which complicates interpretation of that trial's numbers.
- Fibrosis improvement in the MASH trial was modest relative to the MASH-resolution figures, and fibrosis is the endpoint most tied to long-term outcomes.
- Gastrointestinal adverse events reached 89.7% at the 6.0 mg dose in phase 3 — benefit and tolerability are inseparable here.
- No cardiovascular outcome data are published; a dedicated outcomes trial is underway.