Mazdutide

Mazdutide (also designated IBI362 by its developer Innovent Biologics, or LY3305677 under the Eli Lilly licensing code) is a synthetic once-weekly glucagon-like peptide-1 (GLP-1) and glucagon receptor (GCGR) dual agonist. It is a fatty-acid-conjugated peptide designed for subcutaneous weekly dosing, following the pharmacokinetic engineering approach established by semaglutide. Mazdutide is currently in active Phase 2 and Phase 3 clinical development in China and internationally for obesity and type 2 diabetes.

The compound received Breakthrough Therapy Designation from the National Medical Products Administration (NMPA) of China for obesity treatment, accelerating its development pathway. Phase 3 trials are underway; no regulatory approval has been granted in any jurisdiction as of 2025.

Mazdutide engages two distinct receptor systems to produce complementary metabolic effects:

**GLP-1 receptor agonism** suppresses appetite through hypothalamic and brainstem signaling, slows gastric emptying, and stimulates glucose-dependent insulin secretion from pancreatic beta cells. This mechanism is shared with semaglutide and all approved GLP-1 receptor agonists. GLP-1R engagement primarily drives caloric restriction through appetite reduction.

**Glucagon receptor agonism** adds a mechanistically distinct second mode of action. Glucagon receptor activation in the liver promotes beta-oxidation of fatty acids, reduces hepatic lipid accumulation, and stimulates secretion of fibroblast growth factor 21 (FGF21), which further enhances thermogenesis and energy expenditure. GCGR agonism also directly increases energy expenditure through hepatic and peripheral mechanisms, complementing the appetite-based weight loss from GLP-1R engagement. While glucagon is inherently hyperglycemic when administered alone, in the context of simultaneous GLP-1R-driven insulin secretion, the glycemic effect is counterbalanced, producing neutral or modestly improved glycemic control in clinical trials.