Mazdutide (IBI362)
Dual GLP-1/Glucagon Receptor Agonist | Weight Loss & Diabetes
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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.
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.
Molecular Data
33-amino acid linear synthetic peptide Complex or non-standard sequence format
Research Indications
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%.
Dosing Protocols
Subcutaneous injection delivering dual GLP-1/glucagon agonism with once-weekly dosing enabled by fatty acid conjugation.
| Goal | Dose | Frequency | Route |
|---|---|---|---|
| Weight loss initiation (3mg target) | 1.5mg → 3mg | Once weekly | SubQ |
| Weight loss progression (4.5mg target) | 1.5mg → 3mg → 4.5mg | Once weekly | SubQ |
| Weight loss optimization (6mg target) | 2mg → 4mg → 6mg | Once weekly | SubQ |
| Maximum weight loss (9mg target) | 3mg → 6mg → 9mg | Once weekly | SubQ |
| T2D management (mild-moderate) | 3-4.5mg weekly | Once weekly | SubQ |
Reconstitution Instructions
- Mazdutide lyophilized powder vial
- Bacteriostatic water (BAC) for injection
- Insulin syringes (29-31 gauge)
- Alcohol prep pads
- Refrigerator (2-8°C)
- 1 Allow vial to reach room temperature (15-20 minutes)
- 2 Clean vial top with alcohol swab, air dry completely
- 3 Calculate reconstitution volume for desired concentration
- 4 Draw bacteriostatic water into syringe, remove air bubbles
- 5 Inject BAC water slowly down vial side—drop by drop to prevent foaming
- 6 Gently swirl vial in circular motion
- 7 Verify complete clarity and colorless appearance
- 8 Label vial with reconstitution date and concentration
- 9 Store at 2-8°C, use within 30 days
Interactions
What to Expect
Side Effects & Safety
Common Side Effects
- Nausea (mild-moderate, typically improves over time)
- Diarrhea
- Vomiting
- Increased heart rate (5-17 bpm observed)
Stop Signs - Discontinue if:
- Severe or persistent abdominal pain (potential pancreatitis)
- Neck lumps, hoarseness, or difficulty swallowing
- Severe nausea/vomiting preventing adequate nutrition or hydration
- Signs of severe hypoglycemia (confusion, sweating, shakiness)
- Severe allergic reactions (rash, difficulty breathing, facial swelling)
- Unusual mood changes, depression, or suicidal thoughts
- Signs of gallbladder problems (severe upper right abdominal pain)
Contraindications
- Personal or family history of medullary thyroid carcinoma
- MEN2 syndrome history (class warning for GLP-1 agonists)
- Pregnancy or breastfeeding (insufficient safety data)
Quality Checklist
Good Signs
- White to off-white lyophilized powder without clumping or discoloration
- Completely clear and colorless appearance after reconstitution—no visible particles
- Intact vial seal and clear labeling with mg dosage, batch numbers, expiration dates
Warning Signs
- Source verification critical—available from research chemical suppliers
Bad Signs
- Clumping, discoloration, or moisture in powder
- Persistent cloudiness or particles after reconstitution indicates degradation
Frequently Asked Questions
How much weight does mazdutide cause compared to semaglutide?
Mazdutide demonstrated 20.1% weight loss over 60 weeks in Phase 3 trials (GLORY-2), with 48.7% of users achieving ≥20% reduction. This exceeded semaglutide's typical 12-17% losses. The dual GLP-1/glucagon mechanism accounts for superior weight loss and metabolic improvements.
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.
Can I switch from semaglutide to mazdutide?
Potentially, but with medical supervision. Both are GLP-1 agonists, so overlap during transition risks hypoglycemia and severe GI effects. Wait 1-2 weeks after stopping semaglutide before starting mazdutide, and monitor glucose carefully. Never combine them.
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.
- 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.
- 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).
- 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.
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Disclaimer
This information is for educational and research purposes only. Consult a healthcare professional before use.