Mazdutide (IBI362): The Dual GLP-1R/GCGR Agonist

What Is Mazdutide’s Mechanism of Action?

Mazdutide (IBI362) is engineered to simultaneously activate two metabolic receptors: GLP-1R (glucagon-like peptide-1 receptor) and GCGR (glucagon receptor). This dual-agonist design creates a two-pathway mechanism that addresses both appetite regulation and energy expenditure through distinct but complementary biological routes.

The GLP-1 receptor component drives appetite suppression through central hypothalamic signaling, promotes glucose-dependent insulin secretion from pancreatic beta cells, and slows gastric emptying to prolong satiety. These effects mirror the established pharmacology of single GLP-1 agonists such as Semaglutide and form the foundation of Mazdutide's metabolic activity.

The glucagon receptor (GCGR) component introduces a second axis of action. Glucagon receptor activation promotes hepatic lipid oxidation, stimulates thermogenesis, and increases resting energy expenditure. This means the compound does not rely solely on reduced caloric intake; it actively enhances the body's energy utilization, which may contribute to improved fat mass reduction and metabolic outcomes.

The key research insight with Mazdutide is what it omits: GIP receptor agonism. By testing whether GLP-1 combined with glucagon receptor activation—without GIP—produces meaningful metabolic benefits, Mazdutide helps researchers isolate the contribution of each individual receptor. This is critical for understanding the mechanistic basis of multi-agonist efficacy in the incretin class.

The critical difference between these two compounds is the inclusion of GIP receptor agonism. Retatrutide engages all three incretin and metabolic receptors (GLP-1, GIP, and glucagon), while Mazdutide activates only GLP-1 and glucagon. By comparing Mazdutide's GLP-1+GCGR results to Retatrutide's GLP-1+GIP+GCGR results, researchers can infer the approximate contribution of GIP to metabolic outcomes—including the degree to which GIP receptor activation accounts for the difference in weight reduction efficacy between dual and triple agonist compounds.

What Is the Status of China Approval?

Mazdutide received its first regulatory approval in China in 2025 for the treatment of type 2 diabetes, marking a significant milestone in the GLORY clinical trial program. For a broader view of how multi-receptor agonists work, see our triple-agonist pathway analysis. The GLORY program encompasses multiple Phase 3 studies evaluating Mazdutide's efficacy and safety across glycemic control and weight management endpoints in Chinese patient populations.

Innovent Biologics is Mazdutide's developer, having originally licensed the compound from Eli Lilly's incretin pipeline (the same pipeline that produced retatrutide and tirzepatide). This partnership provided Innovent with access to Lilly's GLP-1/glucagon receptor agonist chemistry while granting Innovent primary development and commercialization rights in China. The licensing arrangement reflects a broader industry trend of regional partnerships for incretin-class compounds.

Global Phase 3 clinical trials are ongoing for the obesity indication, with data expected to inform regulatory submissions beyond China. The compound's approval trajectory is being closely watched as it represents the first dual GLP-1R/GCGR agonist to reach market in any territory. China represents the largest single-country market for GLP-1 class compounds, making Mazdutide's commercial and clinical trajectory highly relevant to the global metabolic research landscape. Track all compound timelines on the obesity drug approval tracker. For verified research peptide suppliers, see our best research peptides 2026 guide.