Mazdutide Produces Significant Weight Loss in Adults with Obesity: JAMA

In order to determine the efficacy potential and safety parameters of the combined agonists therapy, scientists conducted an extensive clinical trial among 27 specialist hospitals in China, from December 2023 to November 2025. Study subjects were chosen among adults of Chinese descent, with or without type 2 diabetes, based on their BMI of 30 kg/m2 or more – that is, those suffering from moderate to advanced obesity among the national population. Randomization of the participants was conducted using strict 2:1 ration, assigning one of the two groups to the experimental or placebo treatment protocol, respectively.

The experimental subjects were given a single subcutaneous weekly administration of 9 mg mazdutide, while the placebo subjects were administered placebo treatment once per week, along with reduced calorie and physical activity regimen throughout the 60-week treatment period. The coprimary outcomes monitored by scientists were changes in weight measured as precise percentage difference from baseline until week 60, as well as achievement of ≥ 5% weight loss in comparison with initial weight during the same period.

Key findings:

• In this phase 3 clinical trial, there were 462 individuals allocated to the pooled cohort, and 461 subjects actually received one dose of the investigational drug for the final analysis.
• In detail, there were 307 patients who received the active once weekly 9 mg mazdutide drug in the study arm, and 154 subjects were part of the placebo arm.
• The initial population in the trial had a mean age of 33.9 years, body weight of 94.0 kg, mean BMI of 34.3, females constituted 295 of all subjects (64.0%), while the concurrent proportion of participants with type 2 diabetes were 16.1%. By week 60, the mean percentage body weight change from baseline value showed –16.65% in the study arm versus only –1.50% in the placebo arm (P < .001).
• The difference in mean percent reduction in weight of both arms was found to be −15.15% at week 60. At the same time point, the percentage of patients with body weight reduction by 5% or more was 84.3% in the mazdutide arm versus 33.1% in the placebo arm (P < .001).
• Adverse events leading to the permanent discontinuation of the study treatment occurred in 2.9% of the mazdutide cohort, compared to an absolute 0% within the placebo control group.
• The most common treatment-emergent adverse events reported were vomiting, occurring in 53.1% of the mazdutide group versus 1.3% of the placebo group; nausea, tracking at 46.9% versus 3.2%, respectively; and diarrhea, noting 39.4% versus 6.5%, with the vast majority of these events rated as mild to moderate in severity.

In summary, mazdutide yielded significant weight loss among adults with obesity (moderate to severe) compared to placebo, but there were gastrointestinal side effects in patients on the drug compared to those on placebo. The highly successful results from this multi-center phase 3 study provide a crucial clinical approach to the treatment of obesity in contemporary times, and the combination of GLP-1 and glucagon receptors is an extremely powerful strategy.

Reference:

Gao L, Jiang H, Cai H, et al. Treatment With 9-mg Mazdutide for Weight Reduction in Chinese Adults With Obesity: The GLORY-2 Randomized Clinical Trial. JAMA. Published online June 07, 2026. doi:10.1001/jama.2026.8142