Treatment With 9-mg Mazdutide for Weight Reduction in Chinese Adults With Obesity: The GLORY-2 Randomized Clinical Trial.
The GLORY-2 trial was a double-blind, placebo-controlled, phase 3 randomized clinical trial evaluating the efficacy and safety of mazdutide — a once-weekly subcutaneous glucagon and GLP-1 receptor dual agonist — for weight reduction in Chinese adults with obesity (BMI ≥30). Conducted across 27 hospitals in China from December 2023 to November 2025, the trial enrolled 461 participants (64% female; mean age ~34 years; mean BMI ~34.3), including 16.1% with type 2 diabetes. Participants were randomized 2:1 to receive 9 mg mazdutide or placebo weekly for 60 weeks alongside lifestyle interventions. The co-primary outcomes were percentage change in body weight and proportion achieving ≥5% weight loss at week 60. The mazdutide group achieved a mean body weight reduction of approximately 16.65% from baseline, compared with 1.50% in the placebo group — a statistically significant between-group difference of approximately 15.15%. Gastrointestinal adverse reactions were more common in the mazdutide group than in the placebo group. Key limitations include the single-ethnicity (Chinese) population, limiting generalizability, and a relatively young mean participant age. The trial was industry-relevant and registered on ClinicalTrials.gov (NCT06164873).
Why this grade: This is a phase 3, double-blind, placebo-controlled RCT with a large sample (n=461), pre-registered, conducted in humans over 60 weeks, meeting criteria for strong human evidence, though generalizability is limited to Chinese adults with obesity.
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 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.
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