Mazdutide

Mazdutide (Inj)

Mazdutide (IBI362) is an investigational dual agonist targeting the glucagon-like peptide-1 receptor (GLP-1R) and the glucagon receptor (GCGR). It is studied for weight loss and metabolic effects by reducing appetite via GLP-1R signaling while increasing energy expenditure and affecting hepatic lipid metabolism via glucagon receptor activity.

Dosing Protocols

— 5 mg Vial —

Reconstitute: Add 3.0 mL bacteriostatic water → ~1.67 mg/mL concentration.
Typical weekly range: 2.5–6 mg once weekly with gradual titration.
Easy measuring: At 1.67 mg/mL, 1 unit = 0.01 mL ≈ 16.7 mcg on a U-100 insulin syringe.
Storage: Lyophilized: freeze at −20 °C; reconstituted: refrigerate at 2–8 °C, avoid freeze-thaw cycles.

Schedule: Once-weekly subcutaneous injections for 8–12 weeks minimum.
Cycle Length: Minimum 8 weeks; clinical evidence supports 12–48 week protocols.
Goal: Support chronic weight management and metabolic improvement through dual GLP-1/glucagon receptor activation.

Frequency: Inject once weekly subcutaneously. Gradual titration to improve tolerability.

Phase	Dose	Syringe (U-100)
Weeks 1–4	2.5 mg	150 units (1.50 mL)
Weeks 5–8+	5 mg	300 units (3.00 mL)

— 10 mg Vial —

Reconstitute: Add 3.0 mL bacteriostatic water → ~3.33 mg/mL concentration.
Typical weekly range: 2.5–5 mg once weekly with gradual titration.
Easy measuring: At 3.33 mg/mL, 1 unit = 0.01 mL ≈ 33.3 mcg on a U-100 insulin syringe.
Storage: Lyophilized: freeze at −20 °C; reconstituted: refrigerate at 2–8 °C, avoid freeze-thaw cycles.

Schedule: Once-weekly subcutaneous injections for 8–12 weeks minimum.
Cycle Length: Minimum 8 weeks; clinical evidence supports 12–48 week protocols.
Goal: Support chronic weight management and metabolic improvement through dual GLP-1/glucagon receptor activation.

Frequency: Inject once weekly subcutaneously. Gradual titration to improve tolerability.

Phase	Dose	Syringe (U-100)
Weeks 1–4	2.5 mg	75 units (0.75 mL)
Weeks 5–8+	5 mg	150 units (1.50 mL)

Benefits

• Reduces appetite and caloric intake (GLP-1R-mediated)
• Improves glycemic control via glucose-dependent insulin secretion
• Promotes weight loss in clinical trials (investigational)
• May improve liver fat and metabolic markers (context-dependent)
• May increase energy expenditure via glucagon receptor activity

Mechanism of Action

• GLP-1R activation increases cAMP in β-cells → glucose-dependent insulin secretion
• Delays gastric emptying and increases satiety signaling in CNS
• GCGR activation increases hepatic cAMP → glycogenolysis and thermogenesis signaling
• Net metabolic effect reflects balance of GLP-1 vs glucagon agonism

Side Effects

• Nausea, vomiting, diarrhea
• Constipation
• Reduced appetite
• Reflux or abdominal discomfort
• Increased heart rate
• Possible hypoglycemia when combined with other glucose-lowering agents
• Gallbladder-related events risk (class effect)

Side Effect Management

• Start low and titrate to improve tolerability
• Smaller meals and slower eating can reduce nausea
• Hydration/electrolytes if GI symptoms
• Monitor glucose if combined with insulin/secretagogues
• Stop and evaluate severe abdominal pain (pancreatitis/gallbladder concerns)

Contraindications

• History of medullary thyroid carcinoma or MEN2 (GLP-1RA class precaution)
• History of pancreatitis (caution)
• Severe GI disease (gastroparesis)
• Pregnancy/nursing
• Hypersensitivity

Research Citations

1. Glucagon receptor and energy balance: physiology and pharmacology. Endocr Rev. PubMed | DOI
2. GLP-1 receptor agonists and weight loss mechanisms. Nat Rev Endocrinol. PubMed | DOI
3. Dual GLP-1/glucagon receptor agonists for obesity and diabetes. Diabetes Care. PubMed | DOI

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