Quick summary
Mazdutide is the world's first approved GLP-1/glucagon dual receptor agonist, approved in China in June 2025 as Xinermei. Phase 2 trials showed up to 14.8% weight loss at 48 weeks and up to 80% reduction in liver fat, with US Phase 2 trials ongoing.
Overview
Mazdutide (IBI362, LY3305677) is a once-weekly dual GLP-1 receptor and glucagon receptor agonist developed by Innovent Biologics in partnership with Eli Lilly, modeled on mammalian oxyntomodulin. It became the world's first GLP-1/glucagon dual receptor agonist approved for weight management when China approved it in June 2025 (marketed as Xinermei). Phase 2 trials in Chinese adults showed up to 14.8% weight loss at 48 weeks and up to 80% reduction in liver fat in some cohorts.
Mechanism of action
Mazdutide is a long-acting analogue of oxyntomodulin (OXM), the gut-derived peptide that naturally activates both GLP-1 and glucagon receptors. GLP-1 receptor agonism drives glucose-dependent insulin secretion, suppresses glucagon, slows gastric emptying, and reduces appetite through central hypothalamic signaling — producing the caloric restriction typical of GLP-1 agents. The added glucagon receptor (GCGR) activation increases hepatic fatty acid oxidation and stimulates energy expenditure, directly clearing hepatic lipid accumulation and improving metabolic dysfunction-associated steatotic liver disease (MASLD). GCGR agonism also increases FGF21 secretion, which enhances thermogenesis and peripheral insulin sensitivity. The combination results in weight loss driven by both reduced caloric intake and increased energy expenditure, with pronounced hepatic fat reduction that distinguishes dual agonists from GLP-1-only agents.
Dosing protocols
| Purpose | Route | Dosage | Frequency | Notes |
|---|---|---|---|---|
| Obesity / weight management (clinical trials) | subcutaneous | 3–6 mg | Once weekly | Phase 2 most effective dose: 6 mg weekly. Titrated upward from lower doses. Once-weekly administration. |
Dosing information is for educational purposes only. Consult a qualified healthcare professional before using any peptide.
Research summary
Phase 1b trials in Chinese adults with obesity confirmed tolerability up to 9-10 mg. Phase 2 trials in overweight/obese Chinese adults showed 12% weight loss at 4 mg and 14.8% at 6 mg at 48 weeks vs 0.5% placebo. Liver fat was reduced by up to 80% in some cohorts. Phase 2 T2D data showed significant HbA1c reductions published in Diabetes Care. Phase 3 in China showed clinically meaningful weight loss in Chinese adults with obesity (data May 2025). Approved in China June 2025 for weight management and September 2025 for T2D. US Phase 2 trials ongoing (~179 participants).[1][2][3][4]
Evidence grading
Each claimed benefit is graded by the strength of available evidence. Grades reflect study quality, not effect size.
Strong = multiple RCTs · Moderate = limited trials or observational · Preliminary = animal or in vitro only · Insufficient = anecdotal or no published data
Side effects
Side effects vary by individual. This is not an exhaustive list. Report unusual symptoms to a healthcare professional.
Common stacks
Peptides commonly paired with Mazdutide for synergistic effects.
Legal status
Approved in China as Xinermei for obesity (June 2025) and type 2 diabetes (September 2025). Not approved by the FDA. In Phase 2 development in the United States. Not available outside China or authorized clinical trials. No research chemical or compounding pathway.
Sourcing & access
Research compound
Mazdutide is classified as a research compound. Regulatory status varies by jurisdiction. Always verify current legal status and source from vendors providing third-party certificates of analysis (COA).
Frequently asked questions
Mazdutide (IBI362, LY3305677) is a once-weekly dual GLP-1 and glucagon receptor agonist modeled on mammalian oxyntomodulin, developed by Innovent Biologics with Eli Lilly. It became the first GLP-1/glucagon dual agonist approved anywhere when China approved it in June 2025.
GLP-1 receptor agonism suppresses appetite and slows gastric emptying, while glucagon receptor activation increases hepatic fatty acid oxidation, stimulates energy expenditure, and induces FGF21 secretion for enhanced thermogenesis. This dual mechanism produces weight loss through both reduced intake and increased expenditure.
Common side effects include nausea, diarrhea, vomiting, decreased appetite, injection site reactions, constipation, and abdominal discomfort. The safety profile is consistent with the GLP-1 drug class. It is not FDA-approved and is in Phase 2 development in the United States.
Both are dual-mechanism once-weekly injectables, but they target different receptor pairs. Tirzepatide is GLP-1/GIP while mazdutide is GLP-1/glucagon. The glucagon component gives mazdutide pronounced hepatic fat clearance (up to 80% reduction) compared to GLP-1/GIP agents.
Research references
- A phase 2 randomised controlled trial of mazdutide in Chinese overweight adults or adults with obesityPubMed
- Efficacy and Safety of Mazdutide in Chinese Patients With Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Phase 2 TrialPubMed
- Mazdutide: First ApprovalPubMed
- Once-Weekly Mazdutide in Chinese Adults with Obesity or OverweightPubMed