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

Summary

In a 60-week, double-blind phase 3 RCT across 27 Chinese hospitals (n=461 treated), 9 mg mazdutide yielded a mean −16.65% body-weight change versus −1.50% with placebo and 84.3% achieved ≥5% weight loss. GI adverse events (vomiting, nausea, diarrhea) were common but mostly mild to moderate; discontinuations were low (2.9%).

Key Findings

• Mean percentage weight change at week 60: −16.65% with mazdutide vs −1.50% with placebo (P<0.001)
• ≥5% weight-loss responders: 84.3% with mazdutide vs 33.1% with placebo (P<0.001)
• GI adverse events were common (vomiting 53.1%, nausea 46.9%, diarrhea 39.4%); discontinuation due to AEs was 2.9%

Clinical Implications

Mazdutide provides a potent pharmacologic option for obesity management alongside lifestyle modification, with counseling on GI tolerability and monitoring needed. Findings may inform regional adoption and guideline consideration pending long-term outcomes.

Limitations

• High rates of GI adverse events may limit tolerability in some patients
• Population skewed younger (mean age 33.9 years) which may affect generalizability to older adults or those with multiple comorbidities

Future Directions

Assess durability of weight loss and metabolic benefits beyond 60 weeks, cardiovascular outcomes, comparative effectiveness versus other incretin-based agents, and optimization of dose/escalation strategies.