Once-Weekly Mazdutide in Chinese Adults with Obesity or Overweight.
The GLORY-1 trial was a phase 3, randomized, double-blind, placebo-controlled study conducted in China evaluating mazdutide — a once-weekly injectable glucagon-like peptide-1 (GLP-1) and glucagon receptor dual agonist — for weight management in adults with overweight or obesity. A total of 610 participants (mean BMI 31.1, mean body weight 87.2 kg) were randomly assigned 1:1:1 to receive one of two doses of mazdutide or placebo for 48 weeks. The two co-primary endpoints at week 32 were percent change in body weight and the proportion achieving at least 5% weight reduction, analyzed using a treatment-policy estimand. The study found that both mazdutide groups achieved statistically significant and clinically meaningful reductions in body weight compared to placebo at week 32, with the higher dose group achieving a greater mean reduction than the lower dose group; the placebo group had a marginal mean weight gain. The proportions achieving ≥5% weight loss were substantially higher in both active treatment groups versus placebo. Limitations include the single-country (China) design, limiting generalizability, and the 32-week primary endpoint in a 48-week trial. Safety data were not detailed in the abstract.
Why this grade: This is a phase 3 double-blind, placebo-controlled RCT with 610 participants, providing high-quality direct human evidence for the weight-loss effects of mazdutide, though findings may have limited generalizability beyond Chinese adults.
Background Evidence suggests that incretin-based dual agonist pharmacotherapy is helpful in persons with obesity. Mazdutide, a glucagon-like peptide-1 and glucagon receptor dual agonist, may have efficacy in persons with overweight or obesity. Methods In a phase 3, double-blind, placebo-controlled trial in China, we randomly assigned, in a 1:1:1 ratio, adults 18 to 75 years of age who had a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of at least 28 or had a BMI of 24 to less than 28 plus at least one weight-related coexisting condition to receive 4 mg of mazdutide, 6 mg of mazdutide, or placebo for 48 weeks. The two primary end points were the percentage change in body weight from baseline and a weight reduction of at least 5% at week 32, as assessed in a treatment-policy estimand analysis (which assessed effects regardless of early discontinuation of mazdutide or placebo and the initiation of new antiobesity therapies). Results Among 610 participants, the mean body weight was 87.2 kg and the mean BMI was 31.1 at baseline. At week 32, the mean percentage change in body weight from baseline was -10.09% (95% confidence interval [CI], -11.15 to -9.04) in the 4-mg mazdutide group, -12.55% (95% CI, -13.64 to -11.45) in the 6-mg mazdutide group, and 0.45% (95% CI, -0.61 to 1.52) in the placebo group, and 73.9%, 82.0%, and 10.5% of the participants, respectively, had a weight reduction of at least 5% (P Conclusions In Chinese adults with overweight or obesity, once-weekly mazdutide at a dose of 4 mg or 6 mg for 32 weeks led to clinically relevant reductions in body weight. (Funded by Innovent Biologics; GLORY-1 ClinicalTrials.gov number, NCT05607680.).
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