Mazdutide

Mazdutide, also known by the development codes IBI362 and LY3305677, is an investigational once-weekly injectable peptide that acts as a dual agonist of the glucagon-like peptide-1 (GLP-1) receptor and the glucagon receptor ^[1][3]. It is being developed for chronic weight management and type 2 diabetes and is based on a mammalian oxyntomodulin scaffold, which distinguishes it from single-target GLP-1 receptor agonists by engaging glucagon signaling as well ^[2].

The clinical program has progressed through successive stages in adults with overweight or obesity. An early multiple-ascending-dose phase 1b study established tolerability and showed meaningful short-term weight loss at higher exposures ^[1]. A phase 2 randomized, placebo-controlled trial then demonstrated robust, clinically meaningful body-weight reduction over 24 weeks ^[2], and a further phase 2 study extended evaluation of a higher dose ^[4]. The pivotal GLORY-1 phase 3 trial in Chinese adults with obesity or overweight confirmed substantial weight loss with once-weekly treatment over 48 weeks ^[3]. Beyond weight, the compound is also studied for improvements in cardiometabolic risk factors and liver fat ^[2][3].

Mazdutide is an investigational drug rather than an approved supplement or medicine in most markets, and it has been developed principally through trials conducted in China ^[3]. Its interest lies in the dual-incretin approach: by adding glucagon-receptor activity to the appetite-suppressing effects of GLP-1, it aims to increase energy expenditure and thereby enhance weight loss and metabolic benefit relative to GLP-1-only agents ^[2][3].

As a dual GLP-1/glucagon receptor agonist, mazdutide commonly causes gastrointestinal effects such as nausea, vomiting, diarrhea, and reduced appetite, especially during dose escalation, and it can raise heart rate. Class risks shared with incretin therapies include pancreatitis, gallbladder disease, and hypoglycemia when combined with insulin or sulfonylureas; rodent studies of this drug class have shown thyroid C-cell tumors, so a personal or family history of medullary thyroid carcinoma or MEN2 is a contraindication. It is a newer agent with a limited long-term human safety record.

Mazdutide originated as LY3305677, a GLP-1/glucagon dual agonist discovered by Eli Lilly and subsequently licensed to Innovent Biologics for development in China, where it carries the code IBI362. It is built on a mammalian oxyntomodulin scaffold, the naturally occurring gut hormone that activates both the GLP-1 and glucagon receptors, and it was engineered for once-weekly subcutaneous dosing. Clinical development advanced through phase 1 and 2 studies into a series of phase 3 trials known as the GLORY program, conducted in Chinese adults with obesity or type 2 diabetes. The GLORY-1 trial was published in the New England Journal of Medicine in 2025, and the higher-dose GLORY-2 trial followed in JAMA in 2026.

Mazdutide is widely discussed as one of the most promising entrants in the dual-agonist class, notable for pairing GLP-1 appetite suppression with the added energy-expenditure and hepatic-lipid actions of glucagon-receptor agonism. Commentators highlight its consistent, dose-dependent weight loss, roughly 14 percent at 6 mg and about 16 percent at the 9 mg dose in phase 3, alongside favorable changes in blood pressure, lipids, and liver fat.

It became the first GLP-1/glucagon dual agonist to reach approval in China, which has amplified scientific interest in glucagon co-agonism as a weight-loss strategy. Enthusiasm is tempered by the recognition that its pivotal data come from Chinese populations and that gastrointestinal effects such as nausea and vomiting are common, especially early in treatment. As an incretin-based peptide it remains a prescription therapy rather than a casual supplement.