Strong · human
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).
Strong · human
This systematic review and meta-analysis pooled data from 10 randomized controlled trials (3,236 participants) to evaluate the efficacy and safety of incretin-based dual and triple receptor agonists — specifically tirzepatide, retatrutide, and mazdutide — in overweight or obese adults. The authors searched PubMed, the Cochrane Library, and Google Scholar through June 2025 and applied a random-effects model to pool outcomes. The study found that these agents were associated with statistically significant reductions in body weight (mean difference: −11.47 kg), waist circumference (−9.40 cm), glycated hemoglobin (−0.96%), and fasting plasma glucose (−26.89 mg/dL) compared to placebo. On the safety side, treatment was associated with a higher risk of any adverse event (RR 1.13), gastrointestinal adverse events (nausea, vomiting, diarrhea, constipation), treatment discontinuation due to adverse events (RR 1.96), and hypoglycemic episodes (RR 3.08). No significant difference in serious adverse events was observed. Limitations include the relatively small number of pooled trials, heterogeneity inherent across different agents and doses, and the restriction to placebo-controlled comparisons, which limits conclusions about comparative effectiveness between agents.
Cardiology in review · Feb 2026DOI ↗ Strong · human
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.
The New England journal of medicine · May 2025DOI ↗