Mazdutide 9mg achieves 16.65% body weight reduction in Chinese adults with obesity over 60 weeks
Background
Obesity is a rapidly escalating global health crisis, with a significant public health burden in China. Current pharmacotherapies often fall short in achieving substantial and sustained weight loss, leaving a critical gap in effective treatment options. Mazdutide, a novel dual glucagon and glucagon-like peptide-1 receptor agonist, offers a promising mechanism by simultaneously targeting two key metabolic pathways involved in appetite regulation, energy expenditure, and glucose homeostasis, potentially leading to superior weight loss compared to single-agonist approaches.
Study Design
This double-blind, placebo-controlled, phase 3, randomized clinical trial (GLORY-2) enrolled 461 Chinese adults with obesity (BMI ≥30), including 16.1% with type 2 diabetes. Participants were randomized 2:1 to receive a once-weekly subcutaneous injection of mazdutide 9mg (n=308) or placebo (n=154) for 60 weeks, alongside a reduced-calorie diet and increased physical activity. Coprimary outcomes were the percentage change in body weight from baseline and the proportion of participants achieving at least 5% weight reduction at week 60. Efficacy and safety analyses included participants who received at least 1 dose of the study treatment.
Results
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, significantly greater than the -1.50% (95% CI, -3.43% to 0.43%) observed in the placebo group. The between-group difference was -15.15% (95% CI, -17.22% to -13.09%; P < .001).
Key Findings
- Mazdutide 9mg reduced body weight by -16.65% from baseline at 60 weeks.
- Placebo group achieved only -1.50% body weight reduction at 60 weeks.
- Between-group difference in weight change was -15.15% (P < .001).
- 84.3% of mazdutide recipients achieved ≥5% weight reduction vs. 33.1% with placebo (P < .001).
- Discontinuation due to adverse events was 2.9% in the mazdutide group vs. 0% in placebo.
Why It Matters
Mazdutide 9mg demonstrates a potent new therapeutic option for obesity management, particularly relevant for Chinese adults. The substantial 16.65% mean weight loss and high responder rate (over 84% achieving ≥5% reduction) position it as a highly effective intervention. This could significantly impact clinical practice by offering a powerful alternative or addition to existing GLP-1R agonists, leveraging its dual glucagon receptor agonism for potentially enhanced metabolic benefits. Patients seeking significant weight reduction now have evidence for a higher dose of mazdutide with robust efficacy and a manageable safety profile. Further research into its long-term cardiometabolic benefits and comparative effectiveness against other dual agonists will be crucial for optimizing treatment protocols.
mazdutide
obesity
weight-loss
glp-1-agonist
glucagon-agonist
rct