Treatment With 9-mg Mazdutide for Weight Reduction in Chinese Adults With Obesity: The GLORY-2 Randomized Clinical Trial.

Importance: Obesity is a worldwide problem and a major public health issue in China. Objective: To evaluate the efficacy and safety of mazdutide (a once-weekly glucagon and glucagon-like peptide-1 receptor dual agonist) in Chinese adults with obesity (defined as a body mass index of ≥30). Design, Setting, and Participants: A double-blind, placebo-controlled, phase 3, randomized clinical trial including Chinese adults with or without type 2 diabetes that was conducted at 27 hospitals from December 2023 to November 2025. Interventions: Participants were randomized in a 2:1 ratio to receive a once weekly, 9-mg dose of mazdutide administered subcutaneously (n = 308) or placebo (n = 154) as an adjunct to a reduced calorie diet and increased physical activity for 60 weeks. Main Outcomes and Measures: The coprimary outcomes were the percentage change in body weight from baseline and a weight reduction of at least 5% at week 60. The efficacy and safety analyses were performed in participants who received at least 1 dose of the study treatment. Results: A total of 461 participants (295 [64.0%] female; 16.1% with type 2 diabetes; mean age, 33.9 [SD, 8.4] years; body weight, 94.0 [SD, 13.8] kg; BMI, 34.3 [SD, 3.2]) received the study treatment (307 in the mazdutide group and 154 in the placebo group) and were included in the analyses. At week 60, the mean percentage change in body weight from baseline was -16.65% (95% CI, -18.19% to -15.12%) in the mazdutide group compared with -1.50% (95% CI, -3.43% to 0.43%) in the placebo group (between-group difference, -15.15% [95% CI, -17.22% to -13.09%]; P < .001). At week 60, 84.3% of participants in the mazdutide group had a body weight reduction of 5% or greater compared with 33.1% in the placebo group (between-group difference, 51.6% [95% CI, 43.0% to 60.1%]; P < .001). Adverse events leading to study treatment discontinuation were reported in 2.9% of participants in the mazdutide group compared with 0% in the placebo group. The most common adverse events were vomiting (53.1% in the mazdutide group vs 1.3% in the placebo group), nausea (46.9% vs 3.2%, respectively), and diarrhea (39.4% vs 6.5%); most of the adverse events were mild to moderate in severity. Conclusions and Relevance: Mazdutide provided clinically meaningful weight reduction in Chinese adults with moderate to severe obesity compared with placebo, but participants receiving the drug experienced gastrointestinal adverse reactions compared with those receiving placebo. Trial Registration: ClinicalTrials.gov Identifier: NCT06164873.