Mazdutide
Dual GLP-1/Glucagon Receptor Agonist | Weight Loss & Diabetes
Mazdutide (IBI362/LY3305677) is a first-in-class dual glucagon-like peptide-1 (GLP-1) and glucagon receptor agonist, and a synthetic analog of oxyntomodulin. Unlike tirzepatide which targets GIP/GLP-1, mazdutide uniquely combines GLP-1's appetite suppression with glucagon's ability to stimulate thermogenesis and increase energy expenditure. Phase 3 trials (GLORY-1, GLORY-2) have demonstrated up to 20% weight loss, with recent head-to-head trials showing superiority over semaglutide for both glycemic control and weight reduction in patients with type 2 diabetes and obesity.
Daily dose
3-9mg weekly
Frequency
Once weekly
Cycle length
48-60+ weeks
Storage
2-8°C / -20°C (lyophilized)
Key benefits
Up to 20% body weight loss, superior glycemic control vs semaglutide, increased energy expenditure via glucagon receptor activation, improved cardiometabolic markers (BP, lipids, liver fat), once-weekly convenience
How it works
Dual agonist of GLP-1 and glucagon receptors. GLP-1 activation: stimulates insulin release, suppresses glucagon, slows gastric emptying, reduces appetite. Glucagon activation: increases energy expenditure and thermogenesis, improves hepatic fat metabolism.
Dosage protocols
Goal
Weight loss (3mg target)
Dose
1.5mg → 3mg (weeks 1-4 → 5+) · Once weekly
Route
SubQ injection
Goal
Weight loss (4.5mg target)
Dose
1.5mg → 3mg → 4.5mg · Once weekly
Route
SubQ injection
Goal
Weight loss (6mg target)
Dose
2mg → 4mg → 6mg · Once weekly
Route
SubQ injection
Goal
Maximum weight loss (9mg target)
Dose
3mg → 6mg → 9mg · Once weekly
Route
SubQ injection
Research indications
weight Loss
diabetes
cardiovascular
Administration
Interactions
Safety notes
Start low, escalate gradually every 4 weeks
GI side effects common but typically improve over time
Monitor for pancreatitis symptoms
Caution with history of thyroid cancer
Adjust insulin/sulfonylurea doses to prevent hypoglycemia
Research studies
GLORY-1 Phase 3 Trial - NEJM (2025)
610 Chinese adults with obesity/overweight | 48 weeks | 4mg and 6mg doses
First Phase 3 weight management trial showing clinically meaningful weight reductions with once-weekly mazdutide. Both doses achieved significant weight loss vs placebo with favorable safety profile.
View study →GLORY-2 Phase 3 Trial (2025)
462 Chinese adults with obesity (BMI ≥30) | 60 weeks | 9mg dose
High-dose 9mg mazdutide achieved 20.1% weight loss in non-diabetic participants vs 2.8% placebo. 48.7% achieved ≥20% weight reduction. No plateau observed through week 60.
View study →DREAMS-3 Phase 3 Trial - Head-to-Head vs Semaglutide (2025)
349 Chinese adults with T2D and obesity | 32 weeks | Mazdutide vs Semaglutide
Mazdutide showed superiority over semaglutide on primary endpoint - 48.0% vs 21.0% achieved HbA1c <7.0% AND ≥10% weight reduction (p<0.0001). Mean HbA1c reduction -2.03% vs -1.84%.
View study →Systematic Review & Meta-Analysis - Frontiers (2024)
7 RCTs | 680 participants | 4-24 weeks | Meta-analysis of efficacy and safety
Overall 6.22% greater weight reduction vs placebo. Non-diabetics: 8.44% reduction. Significant improvements in BP, cholesterol, triglycerides. GI side effects most common but transient.
View study →Phase 2 T2D Trial - Diabetes Care (2024)
Chinese adults with T2D | 20 weeks | 3mg, 4.5mg, 6mg doses vs placebo and dulaglutide
HbA1c reductions of 1.41-1.67% with mazdutide vs 0.03% placebo. Weight loss up to 7.1% vs 1.4% placebo. 54-73.5% achieved HbA1c <7.0% target.
View study →Phase 1b High-Dose Safety Trial - eClinicalMedicine (2022)
24 Chinese adults with overweight/obesity | 12 weeks | 9mg and 10mg doses
9mg and 10mg doses were well tolerated with favorable safety profile. 11.7% weight loss at 12 weeks in 9mg cohort. No serious adverse events reported.
View study →