Encyclopedia

Mazdutide is a long-acting synthetic oxyntomodulin analog and dual agonist of the GLP-1 and glucagon receptors, co-developed by Innovent Biologics and Eli Lilly. It is approved as a prescription drug in China for weight management but remains investigational in the United States, with no FDA approval as of this review.

Mazdutide (IBI362 / LY3305677) is a synthetic peptide analog of oxyntomodulin, a naturally occurring gut hormone with dual activity at the glucagon-like peptide-1 receptor (GLP-1R) and glucagon receptor (GCGR). Its peptide backbone incorporates a fatty-acyl modification that extends its in vivo half-life for once-weekly dosing. In published phase 3 Chinese trials, GLORY-1 (NEJM 2025) reported -12.55% body weight at 32 weeks with the 6 mg dose, and GLORY-2 (JAMA 2026) evaluated a 9 mg dose. A head-to-head phase 3 trial versus semaglutide 1 mg in early type 2 diabetes with obesity has also been conducted. Mazdutide has legal prescription status in China for weight management, making it one of the first drugs of its dual GLP-1/glucagon class to reach a regulatory market, but it remains investigational for the US market with no FDA approval. It is a distinct molecular entity from retatrutide (also Lilly-connected) and the two are not interchangeable; no head-to-head trial between them exists.

Mechanism of Action

Dual agonist at the glucagon-like peptide-1 receptor (GLP-1R) and glucagon receptor (GCGR), mimicking the natural gut hormone oxyntomodulin. GLP-1R activity enhances glucose-dependent insulin secretion, slows gastric emptying, and suppresses appetite; GCGR activity adds an energy-expenditure/thermogenic component not present in single GLP-1 agonists. Reported binding affinities: GCGR Ki of 17.7 nM (human) / 15.9 nM (mouse); GLP-1R Ki of 28.6 nM (human) / 25.1 nM (mouse); stimulates insulin secretion in mouse islets with an EC50 of 5.2 nM.