Mazdutide

Research-Grade

Mazdutide (development codes IBI362 / LY3305677) is a dual agonist of the glucagon-like peptide-1 receptor (GLP-1R) and the glucagon receptor (GCGR). It was originally licensed from Eli Lilly to Innovent Biologics and is structurally derived from mammalian oxyntomodulin — a naturally occurring gut hormone that activates both GLP-1 and glucagon receptors. Like other next-generation incretin peptides, it is engineered with a fatty-acid side chain that binds albumin to extend the half-life to a once-weekly dosing interval. The therapeutic logic behind dual GLP-1R/GCGR agonism differs from pure GLP-1 agonists such as semaglutide. The GLP-1 component drives glucose-dependent insulin secretion, slows gastric emptying, and suppresses appetite through central pathways. The glucagon component adds a distinct axis: glucagon increases energy expenditure and promotes hepatic lipid oxidation, which may enhance fat loss and reduce liver fat beyond what GLP-1 signaling alone achieves. The challenge of this class is balancing glucagon's beneficial thermogenic and hepatic effects against its tendency to raise blood glucose — the GLP-1 arm is designed to offset that hyperglycemic pressure. Mazdutide has advanced through a substantial clinical program, predominantly in China. Phase 2 and Phase 3 (GLORY) trials have reported clinically meaningful weight reduction and improvements in glycemic control, hepatic fat, blood pressure, and lipid parameters. In 2025 it received its first regulatory approval in China for chronic weight management. It is not approved by the FDA, EMA, or MHRA, and outside its approved market it circulates as a research compound. Mazdutide sits within the broader shift from single-hormone GLP-1 therapy toward multi-receptor 'polyagonists' — a group that also includes tirzepatide (GLP-1/GIP), survodutide (GLP-1/glucagon), and retatrutide (GLP-1/GIP/glucagon).