Boehringer Ingelheim: Survodutide Phase III shows up to 34% visceral and 63% liver fat reduction with limited lean mass loss
- SYNCHRONIZE-1 (76 weeks) showed sustained weight loss up to 16.6% using the efficacy estimand versus 3.2% with placebo.
- In a SYNCHRONIZE-1 substudy, survodutide reduced visceral fat by up to 34.0% and liver fat by up to 63.1%, while lean mass loss represented no more than 10.8% of total tissue-mass change at the highest dose.
- SYNCHRONIZE-MASLD (48 weeks) met co-primary endpoints: up to 84.2% of survodutide-treated participants achieved ≥30% relative liver fat reduction versus 24.3% on placebo, and up to 12.2% relative body-weight reduction versus 1.0% on placebo.
- Secondary MASLD results: 61.0% of treated patients reached liver fat normalization (<5%) versus 5.7% on placebo; most common adverse events were GI-related with 19% treatment discontinuation due to GI events versus 2.9% for placebo, and no new safety signals identified.
Overview
Boehringer Ingelheim reported positive Phase III results for survodutide (BI 456906), a glucagon/GLP-1 dual agonist, from two trials: SYNCHRONIZE-1 in adults with overweight or obesity without type 2 diabetes (76 weeks), and SYNCHRONIZE-MASLD in adults with overweight or obesity and MASLD with evidence of inflammation and/or fibrosis (48 weeks). Full data were presented at the ADA 2026 Scientific Sessions and published in The New England Journal of Medicine and Nature Medicine.
SYNCHRONIZE-1: body composition and liver fat
The 76-week trial met primary endpoints with sustained weight loss up to 16.6% (efficacy estimand) versus 3.2% for placebo. An MRI-based substudy showed targeted fat loss: visceral fat reduced up to 34.0% and liver fat up to 63.1%. Lean mass loss at the highest dose accounted for no more than 10.8% of the total tissue-mass change, indicating weight loss was primarily fat-driven.
SYNCHRONIZE-MASLD: liver outcomes
The 48-week MASLD trial met both co-primary endpoints: up to 84.2% of participants on survodutide achieved a ≥30% relative reduction in liver fat versus 24.3% with placebo, and body-weight fell up to 12.2% versus 1.0% on placebo. A secondary endpoint showed 61.0% reached liver fat normalization (<5%) versus 5.7% on placebo, with favorable trends in liver biomarkers such as ALT.
Safety and programme next steps
Gastrointestinal events were the most common adverse events, mostly mild to moderate and occurring during dose escalation; discontinuations due to GI events were 19% for survodutide versus 2.9% for placebo. No new safety signals were identified. Survodutide remains investigational; Boehringer is advancing Phase IIIb studies (SYNCHRONIZE-HERA, ELEVATE-LIVER, SYNCHRONIZE-START) and larger Phase III trials (LIVERAGE and LIVERAGE-Cirrhosis) to address additional clinical questions.
Source: Boehringer Ingelheim