Overview
Mazdutide (development code IBI362, also LY3305677) is a once-weekly synthetic peptide agonist of both the GLP-1 receptor and the glucagon receptor, developed by Eli Lilly and licensed to Innovent Biologics for development in China. It belongs to the emerging class of dual incretin/glucagon co-agonists designed to combine the appetite-suppressing and glucose-lowering effects of GLP-1 with the energy-expenditure–raising and hepatic-lipid-mobilizing effects of glucagon.
Structurally, mazdutide is derived from the gut hormone oxyntomodulin, which natively activates both receptors. The peptide has been engineered with substitutions that confer balanced potency at both receptors and conjugated to a C18 fatty acid chain that promotes reversible albumin binding, extending the half-life and enabling once-weekly dosing similar to semaglutide.
Mazdutide is the most advanced GLP-1/glucagon dual agonist in clinical development. The Phase 3 GLORY-1 trial in Chinese adults with obesity reported mean weight loss of approximately 11% with 4 mg and 14% with 6 mg over 48 weeks—comparable to or slightly exceeding semaglutide and approaching tirzepatide-level efficacy. Additional Phase 3 trials in type 2 diabetes (DREAMS-1, DREAMS-2) and NAFLD are ongoing.
Mazdutide received its first regulatory approval in China in June 2025 for chronic weight management in adults with obesity or overweight with at least one weight-related comorbidity. It is not yet approved by the FDA or EMA, and global development outside China is in earlier stages.
Quick facts
- Mechanism
- Dual GLP-1/glucagon receptor agonist for weight loss and metabolic disease
- Primary use
- Chronic weight management; type 2 diabetes; NAFLD research
- Evidence
- moderate
- FDA
- Not approved
- Route
- Subcutaneous injection, once weekly
- Typical results
- Phase 3 GLORY-1 trial reported ~14% mean weight loss at 9 mg over 48 weeks; meaningful HbA1c reductions in T2D
Chemical information
Mazdutide (C₂₁₀H₃₂₂N₄₆O₆₇) is a metabolic compound with a molecular weight of 4563.1 g/mol. Its structural characteristics underpin its biological activity in metabolic regulation and energy homeostasis.
How Mazdutide works
Mazdutide simultaneously activates the GLP-1 receptor (GLP-1R) and the glucagon receptor (GCGR). GLP-1R agonism in pancreatic beta cells potentiates glucose-dependent insulin secretion, in alpha cells suppresses glucagon release, and centrally (hypothalamic POMC neurons, brainstem) reduces appetite and slows gastric emptying. Glucagon receptor agonism in the liver increases fatty acid oxidation and reduces hepatic lipid content, and in adipose tissue and skeletal muscle modestly increases energy expenditure—offsetting the calorie deficit GLP-1 alone produces.
The balance of GLP-1 to glucagon receptor activity is the central pharmacologic design choice for dual agonists. Mazdutide's ratio favors GLP-1 activity (approximately 5:1 GLP-1:GCGR by EC50), preserving robust glucose control while contributing enough glucagon signaling to drive hepatic lipid clearance and incremental energy expenditure without provoking hyperglycemia.
Glucagon-driven lipolysis in the liver is of particular interest for non-alcoholic fatty liver disease (NAFLD/MASH); early hepatic-fat MRI data show mazdutide reduces liver triglyceride content faster and more deeply than GLP-1 monotherapy at comparable weight loss.
Like semaglutide and tirzepatide, mazdutide's albumin-binding fatty acid side chain produces a multi-day half-life (~150 hours), supporting once-weekly subcutaneous dosing. Dose escalation over several weeks is standard to minimize gastrointestinal side effects.
- GLP-1 receptor agonism: Glucose-dependent insulin release, glucagon suppression, appetite reduction, delayed gastric emptying
- Glucagon receptor agonism: Increased hepatic fat oxidation and modest energy-expenditure rise
- Balanced ratio: ~5:1 GLP-1:GCGR potency preserves glucose control while adding lipolytic effects
- Albumin binding: C18 fatty acid chain enables once-weekly dosing
- Hepatic-fat reduction: Pronounced MRI-confirmed liver fat clearance in NAFLD trials
Pharmacokinetics
| Parameter | Value | Significance |
|---|---|---|
| Molecular Mass | 4,563.1 g/mol | Larger than GLP-1 due to lipid conjugation |
| Plasma half-life | ~150 hours | Supports weekly dosing |
| Tmax | ~48 hours post-injection | Slow absorption smooths peak/trough |
| Bioavailability (SC) | High (>85%) | Reliable subcutaneous absorption |
| Elimination | Proteolytic peptide catabolism | No CYP450 interactions |
Dosing & administration
Mazdutide dosing varies by indication and individual factors. No FDA-approved dosing exists for this compound; protocols in the literature derive from limited clinical or preclinical data and practitioner experience.
Any use should be conducted under qualified medical supervision with appropriate monitoring of safety markers.
Important: These dosing ranges are not FDA-approved. Any use should be under qualified medical supervision.
Side effects & safety
Safety data for Mazdutide is primarily derived from preclinical studies and limited human data. Long-term effects in humans remain incompletely characterized.
Common
- • Nausea (most common; typically improves over weeks)
- • Vomiting and decreased appetite
- • Diarrhea or constipation
- • Dyspepsia and abdominal discomfort
- • Injection-site reactions
Serious / potential risks
- • Acute pancreatitis (rare; class warning for GLP-1 agonists)
- • Gallbladder disease, including cholelithiasis
- • Acute kidney injury secondary to dehydration from severe vomiting/diarrhea
- • Hypoglycemia when combined with insulin or sulfonylureas
- • Theoretical thyroid C-cell tumor risk (class warning based on rodent data)
Drug interactions
| Medication | Interaction | Recommendation |
|---|---|---|
| Insulin and sulfonylureas | Additive hypoglycemia risk | Reduce sulfonylurea/insulin dose at mazdutide initiation |
| Oral medications | Delayed gastric emptying may alter absorption | Monitor levels of narrow-therapeutic-index oral drugs |
| Other GLP-1 agonists or co-agonists (semaglutide, tirzepatide) | Additive incretin effects | Do not combine |
| Hormonal contraceptives (oral) | Potentially reduced absorption | Consider supplemental contraception during initiation |
Storage & handling
Lyophilized (powder)
- • Store at -20°C to 4°C (freezer or refrigerator)
- • Protect from light and moisture
- • Stable for 12–24 months when stored properly
- • Keep in original sealed container until reconstitution
Reconstituted solution
- • Refrigerate at 2–8°C after reconstitution
- • Use bacteriostatic water for multi-dose reconstitution
- • Typical stability: 14–28 days refrigerated
- • Do not freeze reconstituted solution
Cost & availability
| Source | Cost | Notes |
|---|---|---|
| Research suppliers | Varies widely | Quality and purity vary significantly between sources |
| Compounding pharmacies | Prescription required | Higher quality assurance and purity testing |
The bottom line
Mazdutide is a metabolic compound with research interest in weight loss, glp-1/glucagon, nafld. While preclinical evidence is encouraging, it remains investigational and is not FDA-approved. Any use should be under qualified medical supervision.
Best for
- • Researchers studying metabolic regulation and energy homeostasis
- • Individuals interested in weight loss under medical guidance
Not for
- • Self-administration without medical supervision
- • Pregnant or breastfeeding individuals
- • Individuals with contraindicated conditions
Related compounds
Semaglutide
Established once-weekly GLP-1 monotherapy benchmark
Tirzepatide
Dual GLP-1/GIP co-agonist with strong weight-loss data
Retatrutide
Triple GLP-1/GIP/glucagon agonist in Phase 3 development
Survodutide
Alternative GLP-1/glucagon dual agonist (Boehringer/Zealand)
Frequently asked questions
References
- [1] Ji L, Jiang H, Bi Y, et al.. Efficacy and safety of mazdutide in Chinese adults with obesity: GLORY-1 randomised trial. Lancet Diabetes Endocrinol (2024). doi: 10.1016/S2213-8587(24)00211-6
- [2] Ji L, Gao L, Jiang H, et al.. Safety and efficacy of mazdutide in Chinese adults with type 2 diabetes: a randomised, placebo-controlled trial. Lancet Diabetes Endocrinol (2023). doi: 10.1016/S2213-8587(23)00131-6
- [3] Boland ML, Laker RC, Mather K, et al.. Resolution of NASH and hepatic fibrosis by the GLP-1/glucagon receptor co-agonist. Nat Med (2020). doi: 10.1038/s41591-020-1126-7 PMID: 33077955