Mazdutide

What it is

Mazdutide (IBI362, LY3305677) is a synthetic peptide derived from oxyntomodulin, a natural gut hormone that activates both the GLP-1 receptor and the glucagon receptor. Eli Lilly designed it, with a fatty acid chain attached so it lasts a week in the blood, and licensed Chinese rights to Innovent Biologics. Lilly keeps the rights elsewhere. ³⁷

China's regulator approved it in June 2025 for weight management in adults with overweight or obesity and at least one weight-related condition, and in September 2025 for type 2 diabetes. In the US it is in phase 2 trials and has no approval; vials sold online as 'research chemicals' are unregulated and not the approved Chinese product. ³⁶

How it works

The GLP-1 side of mazdutide works like semaglutide: it increases insulin release when glucose is high, suppresses glucagon from the pancreas, slows stomach emptying, and reduces appetite through receptors in the brain. ¹⁷

The glucagon receptor side is the novel part. Glucagon normally raises blood sugar by telling the liver to release glucose, which sounds counterproductive, but it also raises energy expenditure and drives the liver to burn fat. The design bet is that the GLP-1 activity cancels the glucose rise while the glucagon activity adds calorie burning and liver fat reduction on top of appetite suppression. Reductions in liver fat and liver enzymes in the trials are consistent with that, though whether energy expenditure actually rises in humans at the trial doses has not been shown directly. ²⁸

What human research shows

GLORY-1 randomized 610 Chinese adults with overweight or obesity to two mazdutide doses or placebo for 48 weeks. Weight fell by 12.0 and 14.8 percent at the lower and higher trial doses versus 0.5 percent on placebo, with improvements in waist circumference, blood pressure, lipids, uric acid, and liver fat. GLORY-2 randomized 461 Chinese adults with obesity (BMI of at least 30) to a higher trial dose or placebo for 60 weeks; weight fell 16.65 percent versus 1.50 percent, and 84 percent versus 33 percent lost at least 5 percent. ⁴¹⁰

The DREAMS-1 and DREAMS-2 trials in type 2 diabetes compared mazdutide with placebo and with dulaglutide, showing larger reductions in HbA1c and weight than dulaglutide. A 2025 systematic review and a 2024 meta-analysis of the randomized trials confirm consistent weight and glycemic effects. A 2026 BMJ network meta-analysis placed mazdutide among the more effective incretin drugs on weight by indirect comparison, but no head-to-head trial against tirzepatide or semaglutide has been published. ³⁵⁹¹¹

The first US trial has now been published. At 24 US centres, 179 adults with obesity or overweight and no diabetes were randomized to one of three mazdutide dose levels or placebo for 48 weeks. At 32 weeks, the primary endpoint, weight fell 7.3, 15.6 and 18.1 percent across the dose levels against 0.9 percent on placebo, with further loss by 48 weeks. Adverse events were mostly gastrointestinal, and one in five participants at the highest dose level stopped treatment because of them. ¹²

Safety

Gastrointestinal effects dominate. In GLORY-2, vomiting affected 53 percent of mazdutide patients versus 1 percent on placebo, nausea 47 versus 3 percent, and diarrhea 39 versus 7 percent, mostly mild to moderate; 2.9 percent stopped because of adverse events. Heart rate rises of a few beats per minute, typical of the class and perhaps more with glucagon activity, were seen. ⁴¹⁰ In the US phase 2 trial, 20 percent of the highest-dose group discontinued for adverse events, mainly gastrointestinal. ¹²

Unknowns include cardiovascular outcomes, long-term safety beyond 60 weeks, effects in non-Chinese populations, and the consequences of glucagon receptor activation over years. Rodent thyroid C-cell findings apply to the GLP-1 class generally. Gray-market vials carry the added risk of unknown purity and dose. ²⁵