Mazdutide
High EvidenceThe first dual GCG/GLP-1 receptor agonist approved in China for obesity and T2D, with Phase 3 showing up to 20.1% weight loss at the 9 mg dose and superiority over semaglutide.
What It Is
Mazdutide (IBI362/LY3305677) is a first-in-class dual glucagon (GCG)/GLP-1 receptor agonist developed by Innovent Biologics in partnership with Eli Lilly. China's NMPA approved mazdutide for chronic weight management in adults with overweight or obesity, making it the first dual GCG/GLP-1 agonist approved anywhere globally. A separate NMPA approval was granted for glycemic control in adults with type 2 diabetes. In the GLORY-1 Phase 3 trial, the 6 mg dose produced 14.01% mean body weight reduction at 48 weeks versus 0.30% with placebo. The GLORY-2 Phase 3 trial of the 9 mg dose achieved up to 20.1% weight loss at 60 weeks in Chinese adults with obesity, with the NDA submission for the 9 mg dose expected in 2026. In the head-to-head DREAMS-3 Phase 3 trial, mazdutide demonstrated superiority over semaglutide in both glycemic control and weight loss in Chinese adults with type 2 diabetes. The GLORY-3 trial is evaluating mazdutide versus semaglutide in adults with obesity and metabolic-associated fatty liver disease (MAFLD), and GLORY-OSA is evaluating mazdutide in obesity with obstructive sleep apnea. Seven Phase 3 studies have been completed or are ongoing. Global regulatory filings outside China are expected.
Regulatory Status
Approved by China's NMPA for chronic weight management (6 mg) and glycemic control in T2D. 9 mg dose NDA pending. Not yet approved by FDA; global regulatory filings expected.
Effective: 2025
View FDA SourceProposed Mechanisms
- GLP-1 receptor agonism reduces appetite and promotes satiety
- Glucagon receptor activation increases energy expenditure and hepatic fat oxidation
- Dual mechanism addresses both caloric intake and metabolic rate
- Improves insulin sensitivity and glucose homeostasis in T2D
- Reduces hepatic lipid accumulation through glucagon-mediated lipolysis
Evidence Snapshot
| Study Type | Model | Outcome | Link |
|---|---|---|---|
| Human (Phase 3) | Chinese adults with obesity (NEJM) | 14.01% weight loss at 48 weeks (6mg) vs 0.30% placebo | Source |
| Human (Phase 3) | Chinese adults with T2D (Nature) | HbA1c reduction of 2.15% (6mg) vs 0.14% placebo at 24 weeks | Source |
| Human (Phase 3) | Head-to-head vs dulaglutide in T2D (Nature) | Superior glycemic control and weight loss vs dulaglutide | Source |
| Human (Phase 3, GLORY-2) | Mazdutide 9 mg in Chinese adults with obesity (60 weeks) | Up to 20.1% weight loss at 60 weeks; met all primary and key secondary endpoints | Source |
| Human (Phase 3, DREAMS-3) | Head-to-head vs semaglutide in Chinese adults with T2D | Superiority over semaglutide in both glycemic control and weight loss | Source |
| Human (Phase 1) | High-dose (up to 10mg) in adults with overweight/obesity | Significant dose-dependent weight reduction | Source |
Commonly Discussed Benefits
Safety & Cautions
- Approved in China only; not yet approved by FDA or EMA
- Phase 3 data primarily in Chinese populations; global trials needed
- Gastrointestinal side effects are the most common adverse events
- Long-term cardiovascular outcome data not yet available
- 9 mg high-dose NDA under review by NMPA
Comparisons
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Citations
- [1] Once-Weekly Mazdutide in Chinese Adults with Obesity or Overweight, NEJM 2025 PubMed
- [2] Mazdutide versus placebo in Chinese adults with T2D, Nature 2025 PubMed
- [3] Mazdutide versus dulaglutide in Chinese adults with T2D, Nature 2025 PubMed
- [4] GLORY-2: Mazdutide 9 mg achieves up to 20.1% weight loss — PRNewswire 2026 PubMed
- [5] DREAMS-3: Mazdutide shows superiority over semaglutide — Innovent 2026 PubMed
- [6] Innovent announces NMPA approval for T2D — PRNewswire 2026 PubMed
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