Mazdutide (IBI362): Research Overview
Dual GLP-1 and glucagon receptor agonist in late-stage trials, developed primarily in China.
Also known as IBI362 · LY3305677
What is Mazdutide?
First-in-class dual GLP-1 and glucagon receptor agonist combining appetite suppression with thermogenesis stimulation. Phase 3 trials demonstrated superiority over semaglutide for weight loss and glycemic control.
What is Mazdutide researched for?
- GLORY-2 demonstrated 20.1% weight loss with 9mg over 60 weeks; 48.7% achieved ≥20% reduction.
- Significant reductions in waist circumference, systolic BP (-7.57 mmHg), triglycerides (-43%).
- Exploratory analysis showed 80.2% reduction in liver fat, suggesting MASLD/MASH benefits.
- HbA1c reductions of 1.41-2.03% across trials; DREAMS-3 showed -2.03% vs semaglutide -1.84%.
- 48% achieved HbA1c <7.0% AND ≥10% weight loss versus 21% with semaglutide.
- Systolic reduction of -7.57 mmHg, diastolic -2.98 mmHg in clinical trials.
- Total cholesterol -16.82%, triglycerides -43.29%, LDL -17.07%.
How does Mazdutide work?
Dual agonist activation: GLP-1 stimulates insulin, suppresses glucagon, slows gastric emptying; Glucagon increases energy expenditure and thermogenesis while GLP-1 counteracts glucose-raising effects.
Reported targets: glucagon receptor
References
GLORY-1 Phase 3 Trial
2025
610 Chinese adults with obesity/overweight; 48 weeks. First Phase 3 weight management trial showing clinically meaningful weight reductions. NEJM.
Controlled clinical trial
GLORY-2 Phase 3 Trial
2025
462 Chinese adults with obesity; 60 weeks; 9mg dose. 20.1% weight loss vs 2.8% placebo; 48.7% achieved ≥20% reduction; no plateau observed.
Controlled clinical trial
DREAMS-3 Phase 3 Trial - Head-to-Head vs Semaglutide
2025
349 Chinese adults with T2D and obesity; 32 weeks. Mazdutide superiority: 48% vs 21% achieved HbA1c <7.0% AND ≥10% weight reduction (p<0.0001).
Controlled clinical trial
Phase 2 T2D Trial
2024
Chinese adults with T2D; 20 weeks. HbA1c reductions 1.41-1.67% vs 0.03% placebo; weight loss up to 7.1%. Diabetes Care.
Controlled clinical trial
Common questions
Why does mazdutide cause thermogenesis while semaglutide doesn't?
Mazdutide's glucagon receptor agonism increases energy expenditure and thermogenesis—burning calories actively rather than just reducing appetite. Semaglutide is GLP-1 only. This dual-agonist approach explains mazdutide's superior metabolic rate elevation.
Is mazdutide safer than semaglutide for nausea?
Not necessarily. Both cause GLP-1-induced nausea early in treatment, though it typically improves with dose escalation. Mazdutide's additional heart rate increase (5-17 bpm) from glucagon agonism is a distinct side effect requiring cardiovascular monitoring.