Mazdutide is a long-acting dual GLP-1 and glucagon receptor agonist for obesity and type 2 diabetes, reducing appetite, improving metabolism, and regulating glucose. Early trials show significant weight reduction and metabolic improvements.
Mazdutide
Also known as: OXM3; IBI362; LY3305677
Overview
Benefits
- Weight reduction
- Improved insulin sensitivity
- Glucose control
- Appetite control
- Cardiovascular health
Consider This Peptide If You Want To
- Support weight loss by enhancing satiety and regulating intake
- Improve metabolic health and glycemic control
Dosage & Administration
Dosage Guidelines
Recommended Dosage
• Amount:3 mg
• Frequency:weekly
• Duration:8 weeks
• Rest Period:8 weeks
• Time of Day:morning
• Ingestion:subcutaneous
Administration Routes:Subcutaneous
Research Findings on Dosage:
• Subcutaneous Injection:
◦ Commonly Reported Dosage: Initial doses typically start at 3 mg, escalating to 6 mg, with higher doses (9 mg) under investigation for advanced cases. (Once weekly)
◦ Duration: 4-24 weeks
Mechanism of Action
Mechanism of Action
How this peptide works in the body
GLP-1 Receptor Activation:
Mazdutide binds to glucagon-like peptide-1 receptors (GLP-1R) on pancreatic beta cells, stimulating glucose-dependent insulin secretion through activation of the cAMP/protein kinase A (PKA) pathway. Concurrently, it inhibits glucagon release from alpha cells, reducing hepatic glucose production and lowering postprandial hyperglycemia. In the central nervous system (CNS), Mazdutide activates pro-opiomelanocortin (POMC) neurons and inhibits neuropeptide Y (NPY)/AgRP neurons in the arcuate nucleus (ARC) of the hypothalamus, delaying gastric emptying and promoting prolonged satiety, leading to reduced caloric intake.
Glucagon Receptor Activation:
Mazdutide binds to glucagon receptors (GCGR) in the liver, stimulating adenylate cyclase (AC) and increasing cAMP levels, which promotes hepatic glucose output and enhances lipolysis. While glucagon typically increases blood glucose, its co-activation with GLP-1R helps counterbalance hyperglycemia, preventing excessive glucose spikes. Additionally, glucagon receptor activation enhances brown adipose tissue (BAT) thermogenesis via uncoupling protein 1 (UCP1), leading to increased energy expenditure and fat oxidation, which contributes to body weight reduction.
Metabolic Benefits Synergy:
By simultaneously activating GLP-1R and GCGR, Mazdutide enhances insulin sensitivity through the AMP-activated protein kinase (AMPK) pathway, facilitating glucose uptake in skeletal muscle and reducing hepatic steatosis. It also lowers plasma triglycerides and LDL cholesterol levels while increasing fatty acid oxidation, improving lipid profiles and cardiovascular health. This synergistic metabolic effect makes Mazdutide a promising therapeutic agent for obesity, metabolic syndrome, and type 2 diabetes.
Consider Stacking With
- Semaglutide (GLP-1RA)
- Thymosin Alpha-1 (Tα1)
- GHK-Cu
Side Effects & Cautions
Common Side Effects
- Injection site redness/itching
- Nausea
- Diarrhea
- Abdominal bloating
Research & References
Research Highlights
Phase 1b Study: Mazdutide showed an average 9.8% weight loss in 12 weeks at 9 mg doses, demonstrating robust efficacy in early-stage trials.
Phase 2 Trial (2023): Significant reductions in body weight (up to 11.3% over 24 weeks) and metabolic improvements, with tolerability profiles comparable to established GLP-1RAs.
Cardiometabolic Impact: Trials revealed improvements in HbA1c, blood pressure, lipid profiles, and reductions in waist circumference.
References
Ji, L., et al., "A phase 2 randomized controlled trial of mazdutide in Chinese overweight adults or adults with obesity," Nat Commun, 2023
Innovent Biologics Clinical Trial Report, 2023
Ambery, P., et al., "GLP-1 and glucagon receptor dual agonists in obesity management," Lancet Diabetes Endocrinol, 2021
Gorgojo-Martínez, J.J., et al., "Clinical recommendations for GLP-1 receptor agonists," J Clin Med, 2023