PMID-40421736 – Mazdutide Phase 3 GLORY-1 Obesity
Zhang Y, Ji L, Hu Y, et al. Once-Weekly Mazdutide in Chinese Adults with Obesity or Overweight. N Engl J Med. 2025;392(22):2135-2146.
Quick Reference
| Property | Value |
|---|---|
| PMID | 40421736 |
| DOI | 10.1056/NEJMoa2413109 |
| Year | 2025 |
| Journal | New England Journal of Medicine |
| Study Type | RCT (Phase 3, randomized, double-blind, placebo-controlled) |
| Evidence Level | I |
| Sample | n=610 Chinese adults with obesity or overweight |
| Peptide(s) Studied | Mazdutide |
Key Findings
- At week 48, mean percentage change in body weight from baseline was -11.0% (4 mg), -14.0% (6 mg), and +0.3% (placebo)
- Statistically significant superiority over placebo for both doses (p<0.001)
- Clinically meaningful improvements in waist circumference, blood pressure, and metabolic markers
- Proportion achieving >=5% weight loss was significantly higher in both mazdutide groups vs. placebo
- Safety profile consistent with GLP-1 class; most common AEs were GI-related (nausea, diarrhea, vomiting)
Study Design
GLORY-1: randomized, double-blind, placebo-controlled Phase 3 trial. Chinese adults aged 18-75 with BMI >=28 kg/m2 or >=24 kg/m2 with weight-related comorbidity. Randomized 1:1:1 to mazdutide 4 mg, mazdutide 6 mg, or placebo subcutaneously once weekly for 48 weeks. Primary endpoint: percent change in body weight from baseline to week 48. Dose-escalation scheme used.
Limitations
- Chinese population — Phase 3 trials in Western populations not yet published
- No head-to-head comparison with semaglutide, tirzepatide, or survodutide
- 48-week duration — longer-term data (2+ years) needed for chronic weight management
Clinical Relevance
This landmark NEJM publication provided the registration-enabling data for mazdutide's approval in China (June 2024 initially for 6 mg, subsequently expanded). The 14% weight loss at 48 weeks with the 6 mg dose is competitive with semaglutide 2.4 mg and approaches tirzepatide efficacy. The dual GLP-1/glucagon mechanism provides a differentiated metabolic profile with potential advantages for hepatic steatosis. The DREAMS-3 head-to-head trial vs. semaglutide is underway.
Related
#research #RCT #mazdutide #evidence-level-I #metabolic