A dual GLP-1/glucagon receptor agonist in Phase 3 trials for obesity and MASH with potent liver fat reduction.
Survodutide (BI 456906) is an investigational dual agonist of the GLP-1 and glucagon receptors, developed by Boehringer Ingelheim in partnership with Zealand Pharma. It combines GLP-1 receptor agonism (appetite suppression, improved insulin sensitivity) with glucagon receptor agonism (increased energy expenditure, hepatic fat oxidation).
The glucagon component distinguishes survodutide from tirzepatide (which uses GIP instead of glucagon). Glucagon receptor activation increases liver fat oxidation, making survodutide particularly promising for MASH (metabolic dysfunction-associated steatohepatitis) — formerly called NASH. This mechanism specifically targets liver fat accumulation, a major unmet medical need.
Phase 2 results for both obesity and MASH have been highly promising, with the drug entering Phase 3 trials for both indications.
Phase 2 results in obesity showed up to 18.7% weight loss at 46 weeks — competitive with tirzepatide. In MASH, survodutide achieved histological resolution of steatohepatitis in up to 83% of patients and fibrosis improvement in up to 52% — the highest rates reported for any investigational MASH therapy.
The MASH results are particularly significant because liver fibrosis improvement was demonstrated — going beyond just fat reduction to actual reversal of structural liver damage. Phase 3 trials (SYNCHRONIZE program) for both obesity and MASH are underway.
📚 Key Reference: PMID: 37840244 (survodutide obesity Phase 2)
GI side effects similar to other GLP-1 agents. Glucagon component raises theoretical concerns about blood glucose elevation in diabetics, though clinical data shows this is counterbalanced by GLP-1 effects. Heart rate increases observed. Full safety profile pending Phase 3 completion.
NOT FDA-approved. In Phase 3 clinical trials for obesity and MASH. Breakthrough Therapy designation for MASH.