Survodutide: Dual Glucagon/GLP-1 Agonist (Boehringer Ingelheim)
Weekly GCGR/GLP-1 dual agonist in Phase 3 for obesity, MASH, T2D. ~19% weight loss at 46 weeks in Phase 2.
👥 Human studies
- Full name
- Survodutide (BI 456906)
- Class
- Glucagon receptor / GLP-1 receptor dual agonist
- Half-life
- ~6.2 days
- Route
- Subcutaneous weekly
- Developer
- Boehringer Ingelheim / Zealand Pharma
- Regulatory status
- Phase 3 SYNCHRONIZE-1/2 met primary endpoints December 2025 (Lancet D&E, January 2026); NDA filed with FDA February 2026. Also Phase 3 in MASH (LIVERAGE). Boehringer Ingelheim / Zealand.
What it is
Survodutide combines GLP-1 agonism with glucagon receptor (GCGR) activation. Glucagon activation increases hepatic fat oxidation and energy expenditure — complementing GLP-1's central anorectic effects. Among the furthest-advanced dual GCGR/GLP-1 agents.
How it works
Dual receptor engagement means satiety and glucose regulation from GLP-1 plus increased energy expenditure, reduced hepatic lipid accumulation, and enhanced thermogenesis from glucagon signalling.
Glucagon's hyperglycaemic risk is balanced by the GLP-1 insulinotropic effect; net glycaemia typically improves in T2D.
What the research shows
Phase 2 obesity (le Roux et al. 2024) and MASH (Sanyal et al. 2024) datasets support Phase 3 pivotal trials.
le Roux CW et al. (2024) — Phase 2 obesity
le Roux C.W. et al., Lancet 2024;403:1085–1099. 👥 Human studies
387 adults with obesity, 46 weeks. Doses 0.6/2.4/3.6/4.8 mg weekly vs placebo.
Weight loss 6.2–18.7% vs 2.0% placebo. Top dose approaches tirzepatide territory.
Limitations: GI adverse events frequent; 18% discontinuation at high dose.
Sanyal AJ et al. (2024) — MASH Phase 2
Sanyal A.J. et al., NEJM 2024;391:311–319. 👥 Human studies
293 patients with biopsy-confirmed MASH and F1–F3 fibrosis.
MASH resolution 47–62% vs 14% placebo; fibrosis improvement secondary.
Limitations: Requires confirmation in larger Phase 3.
Safety and limitations
GI effects dose-dependent. Glucagon-driven heart-rate elevation noted — ~5 bpm. Injection-site reactions 10%.
Theoretical concerns about long-term glucagon activation (hepatic insulin resistance, aminotransferase rise) remain under monitoring.