Survodutide

Survodutide (BI 456906) is a dual glucagon receptor (GCGR) and GLP-1 receptor (GLP-1R) agonist developed by Boehringer Ingelheim and Zealand Pharma. It is in Phase 3 trials for obesity and overweight (SYNCHRONIZE program) and received FDA Fast Track Designation for metabolic dysfunction-associated steatohepatitis (MASH/NASH). The dual mechanism adds hepatic fat clearance and energy expenditure on top of appetite suppression.

Survodutide simultaneously activates two distinct receptor pathways. GLP-1 receptor agonism slows gastric emptying, enhances glucose-dependent insulin secretion, and reduces appetite via central hypothalamic signaling — effects shared with semaglutide and tirzepatide. The added glucagon receptor (GCGR) agonism introduces direct hepatic mechanisms not present in GLP-1-only agents: stimulation of mitochondrial fatty acid beta-oxidation, upregulation of energy expenditure through farnesoid X receptor (FXR) signaling, and induction of fibroblast growth factor 21 (FGF21) secretion. FGF21 is a key metabolic hormone that increases thermogenesis and improves insulin sensitivity. Together, the dual agonism increases both energy expenditure and reduces caloric intake, producing weight loss that may exceed GLP-1-only agents in certain populations.

Phase 2 data showed mean weight loss ranging from 6.2% (0.6 mg) to 14.9% (4.8 mg) at 46 weeks vs 2.8% for placebo. In the Phase 2 MASH trial, up to 62% of patients at 4.8 mg achieved histological MASH improvement without worsening fibrosis, vs 14% placebo. Phase 3 SYNCHRONIZE-1 (obesity without T2D) and SYNCHRONIZE-2 (obesity with T2D) trials are ongoing globally, with SYNCHRONIZE-CVOT evaluating long-term cardiovascular safety. Results pending as of 2026.

Peptides commonly paired with Survodutide for synergistic effects.