Mazdutide
Dual GLP-1/Glucagon Receptor Agonist | Weight Loss & Diabetes
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.
Mechanism of Action
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.
Key Benefits
- Up to 20% body weight loss
- Superior glycemic control versus semaglutide
- Increased energy expenditure via glucagon receptor activation
- Improved cardiometabolic markers (BP, lipids, liver fat)
- Once-weekly injection convenience
33-amino acid linear synthetic peptide Complex or non-standard sequence format
Weight Loss
- Severe Obesity Management
GLORY-2 demonstrated 20.1% weight loss with 9mg over 60 weeks; 48.7% achieved ≥20% reduction.
- Metabolic Syndrome Improvement
Significant reductions in waist circumference, systolic BP (-7.57 mmHg), triglycerides (-43%).
- Liver Fat Reduction
Exploratory analysis showed 80.2% reduction in liver fat, suggesting MASLD/MASH benefits.
Type 2 Diabetes
- Glycemic Control
HbA1c reductions of 1.41-2.03% across trials; DREAMS-3 showed -2.03% vs semaglutide -1.84%.
- Dual Endpoint Achievement
48% achieved HbA1c <7.0% AND ≥10% weight loss versus 21% with semaglutide.
Cardiovascular
- Blood Pressure Reduction
Systolic reduction of -7.57 mmHg, diastolic -2.98 mmHg in clinical trials.
- Lipid Profile Enhancement
Total cholesterol -16.82%, triglycerides -43.29%, LDL -17.07%.
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
Both are GLP-1 agonists; combining increases hypoglycemia and severe GI side effect risk.
Both target GLP-1 receptor; additive effects on GI symptoms and hypoglycemia risk.
Another GLP-1 agonist; dual therapy contraindicated due to additive receptor activation.
May require significant dose reduction due to improved glucose control; monitor for hypoglycemia.
Increased hypoglycemia risk; dose reduction may be necessary.
Complementary mechanisms; clinical trials allowed stable metformin use with enhanced efficacy.
No known interactions; may support gut health and potentially reduce GI side effects.
Delayed gastric emptying may affect absorption; separate administration by 1 hour.
Appetite reduction, possible mild nausea, decreased portion sizes
Early weight loss begins (1-2%), improved satiety after meals
Dose escalation phase, GI symptoms typically improving, 3-5% weight loss
Steady weight loss continues (7-12%), energy expenditure effects evident
Significant weight reduction (12-17%), metabolic markers improving
Peak effects (up to 20% weight loss), sustained improvements in BP, lipids, glucose
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)
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
- 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.
Disclaimer
This information is for educational and research purposes only. Consult a healthcare professional before use.