Mazdutide, a GLP-1/glucagon dual agonist developed in China, achieved up to 14% body weight loss at 48 weeks with very low dropout rates in a 610-person phase 3 trial published in the New England Journal of Medicine.
-14.01% body weight at 48 weeksThe 6 mg mazdutide dose achieved this weight reduction vs. +0.30% for placebo (p<0.001), with half of participants losing 15% or more
What the researchers found
In this phase 3 NEJM-published trial (GLORY-1), mazdutide — a GLP-1/glucagon dual agonist — produced significant weight loss in 610 Chinese adults with obesity or overweight over 48 weeks. The 6 mg dose achieved 14.01% body weight reduction at week 48 (vs. 0.30% for placebo), and the 4 mg dose achieved 11.00%. At week 48, 49.5% of participants on the 6 mg dose lost ≥15% of their body weight. Both doses improved all prespecified cardiometabolic measures. Discontinuation rates due to adverse events were remarkably low (0.5-1.5%), with GI side effects being mostly mild to moderate.
Why it matters
Mazdutide is China's homegrown competitor to tirzepatide and semaglutide, and this NEJM publication validates it as a serious contender. Its dual GLP-1/glucagon mechanism differs from tirzepatide's GLP-1/GIP approach, potentially offering distinct metabolic benefits. The very low discontinuation rate is particularly notable for a weight loss drug.
The numbers in context
n=610 · 48 weeks · 6 mg: -14.01% weight · 4 mg: -11.00% weight · Placebo: +0.30% · ≥5% loss: 82% (6 mg) · ≥15% loss: 49.5% (6 mg) · Discontinuation: 0.5-1.5% · p<0.001 all comparisons
How the study worked
Phase 3, double-blind, placebo-controlled, randomized trial (GLORY-1) conducted in China. 610 adults aged 18-75 with BMI ≥28 (or ≥24 with comorbidities) were randomized 1:1:1 to mazdutide 4 mg, mazdutide 6 mg, or placebo for 48 weeks. Co-primary endpoints were percentage body weight change and proportion achieving ≥5% weight loss at week 32 using treatment-policy estimand analysis.
Who was studied
610 Chinese adults aged 18-75 with obesity (BMI ≥28) or overweight (BMI 24-28) with at least one weight-related comorbidity
What this study cannot tell us
Conducted exclusively in Chinese adults, so results may not generalize to other populations with different BMI distributions and metabolic profiles. Chinese BMI thresholds for obesity (≥28) and overweight (≥24) are lower than Western standards. No active comparator arm (e.g., semaglutide or tirzepatide), so direct comparison with existing drugs requires cross-trial interpretation. 48 weeks is meaningful but not long-term safety data.
How to read the evidence
Rated strong because this is a large (n=610), phase 3, double-blind, placebo-controlled randomized trial published in the New England Journal of Medicine — the gold standard for clinical evidence. Results were highly significant across all endpoints.
When this study was published
Published in 2025 in NEJM, this is the pivotal trial supporting mazdutide's regulatory path. It represents the most current evidence for this drug.
The bigger picture
The weight loss drug market has been dominated by Novo Nordisk (semaglutide) and Eli Lilly (tirzepatide), both Western companies. Mazdutide from Innovent Biologics represents China's entry into this space with a distinct mechanism — targeting glucagon rather than GIP as the second receptor. This NEJM publication signals that mazdutide is a serious global competitor. Its unique GLP-1/glucagon mechanism may offer metabolic advantages, particularly for liver fat reduction, that differ from GLP-1/GIP drugs.
Questions still open
- How does mazdutide compare head-to-head with semaglutide and tirzepatide in terms of weight loss and tolerability?
- Does the glucagon receptor component provide additional benefits for liver fat (MASH/NASH) beyond what GLP-1 alone achieves?
- Will the results hold up in non-Asian populations where baseline BMI and metabolic profiles differ?
Common questions
How does mazdutide differ from semaglutide and tirzepatide?
Is mazdutide available outside of China?
Read the original research
Once-Weekly Mazdutide in Chinese Adults with Obesity or Overweight.
The New England journal of medicine, 392(22), 2215-2225
Citation
Ji, Linong; Jiang, Hongwei; Bi, Yan; Li, Hua; Tian, Junhang; Liu, Dexue; Zhao, Yuzhu; Qiu, Wei; Huang, Chongbing; Chen, Lei; Zhong, Shao; Han, Jie; Zhang, Yawei; Lian, Qiufang; Yang, Ping; Lv, Lingchun; Gu, Jieyu; Liu, Zihan; Deng, Huan; Wang, Yanqi; Li, Li; Pei, Lijuan; Qian, Lei. (2025). Once-Weekly Mazdutide in Chinese Adults with Obesity or Overweight.. The New England journal of medicine, 392(22), 2215-2225. https://doi.org/10.1056/NEJMoa2411528