Mazdutide
From PeptidePlaza, the free peptide reference · Entry #034 · Metabolic · Hand-curated entry · Editorial standards
Mazdutide (also known as IBI362, LY3305677, OXM analogue, Xinermei) is a metabolic research peptide. An oxyntomodulin-based dual agonist and the first GLP-1/glucagon co-agonist approved anywhere in the world — cleared in China for weight management in 2025.
Mazdutide is a mammalian oxyntomodulin analogue that agonises both the GLP-1 receptor and the glucagon receptor, originally developed by Eli Lilly and licensed to Innovent Biologics for China. Unlike survodutide, which is a synthetic co-agonist scaffold, mazdutide is built directly on oxyntomodulin — the endogenous gut hormone that natively hits both receptors. It became the first GLP-1/glucagon dual agonist to receive full regulatory approval for obesity anywhere in the world when China's NMPA cleared it for chronic weight management in June 2025, followed by approval for glycaemic control in type 2 diabetes in September 2025 (marketed as Xinermei). In the phase 3 GLORY-1 trial (N=610 Chinese adults with obesity or overweight plus comorbidity), placebo-subtracted weight reduction at week 32 was approximately 10.5% at 4 mg and 13.0% at 6 mg, widening to approximately 11.3% and 14.3% by week 48; about 74% (4 mg) and 83% (6 mg) achieved ≥5% weight loss versus 11.5% on placebo. The GLORY-2 study of the higher 9 mg dose reported up to 20.1% weight loss. Beyond weight, trials reported reductions in waist circumference, blood lipids, blood pressure, serum uric acid, liver enzymes and hepatic fat, plus improved insulin sensitivity — the uric acid and liver signals being characteristic of glucagon receptor engagement.
1 Mechanism of action
Dual agonism at GLP-1R and GCGR from an oxyntomodulin backbone. GLP-1R activation drives satiety, glucose-dependent insulin secretion and delayed gastric emptying; GCGR activation increases energy expenditure, hepatic lipolysis and fatty acid oxidation, and lowers hepatic fat and serum uric acid.
Primary targets: GLP-1R · GCGR
2 Reported effects
Effects below are those reported in the published literature cited on this page. They are not claims of clinical benefit and not medical advice.
2.1 Reported benefits
- First GLP-1/glucagon dual agonist approved for obesity (China, 2025)
- Up to 20.1% weight loss at the 9 mg dose (GLORY-2)
- Reductions in hepatic fat content and liver enzymes
- Lowers serum uric acid — unusual among incretin therapies
- Improves blood pressure, lipids and insulin sensitivity
- Once-weekly subcutaneous dosing
2.2 Side effects
- Nausea, vomiting, diarrhoea (dose-dependent, mostly during escalation)
- Decreased appetite
- Increased heart rate
- Injection site reactions
- Transient hepatic enzyme changes
- Hypoglycaemia when combined with insulin secretagogues
3 Chemical and physical properties
| CAS number | 2259884-03-0 |
|---|---|
| Molar mass | ~4,300 g/mol |
| Purity (typical) | >98% |
| Half-life | ~7 days (SC injection; weekly dosing) |
| Storage | −20 °C, lyophilised powder, desiccated |
| Solubility | Sterile water / bacteriostatic water |
| Receptors / targets | GLP-1R, GCGR |
3.1 Amino acid sequence
Acylated oxyntomodulin analogue (GLP-1/glucagon dual agonist backbone with fatty acid side chain)
4 Research dosages
Approved Chinese weight-management dosing: 4 mg or 6 mg SC once weekly after escalation. GLORY-2 evaluated 9 mg weekly.
5 Research studies (8)
- Once-Weekly Mazdutide in Chinese Adults with Obesity or Overweight (GLORY-1)
New England Journal of Medicine (2025) · RCT · N=610Phase 3 randomised placebo-controlled trial of mazdutide 4 mg and 6 mg over 32 weeks with extension to week 48.Key finding: Placebo-subtracted weight reduction of ~10.5% (4 mg) and ~13.0% (6 mg) at week 32, widening to ~11.3% and ~14.3% by week 48. - Mazdutide: First Approval
Drugs (2025) · Review · N/A (review)Regulatory and development profile of mazdutide following its Chinese approval.Key finding: First GLP-1/glucagon receptor dual agonist to receive regulatory approval for chronic weight management. - Novel GLP-1-based Medications for Type 2 Diabetes and Obesity.
Endocrine reviews (2026) · ReviewThe approvals of semaglutide and tirzepatide have set new benchmarks in the treatment of type 2 diabetes and obesity. - Beyond weight loss: multisystem benefits of obesity medications.
The lancet. Diabetes & endocrinology (2026) · ReviewObesity is increasingly managed with medications as disease-modifying therapies, reflecting its role as a gateway disease driving metabolic, cardiovascular, reproductive, neuropsychiatric, and mechanical... - Comparative effects of drugs for adults with overweight or obesity: systematic review and network meta-analysis.
BMJ (Clinical research ed.) (2026) · Systematic ReviewObesity drugs produce variable weight loss at one year, with larger benefits generally accompanied by greater harms and discontinuation. - Once-Weekly Mazdutide in Chinese Adults with Obesity or Overweight.
The New England journal of medicine (2025) · RCTIn Chinese adults with overweight or obesity, once-weekly mazdutide at a dose of 4 mg or 6 mg for 32 weeks led to clinically relevant reductions in body weight. - Emerging pharmacotherapies for obesity: A systematic review.
Pharmacological reviews (2025) · Systematic ReviewThe history of antiobesity pharmacotherapies is marked by disappointments, often entangled with societal pressure promoting weight loss and the prevailing conviction that excess body weight signifies a lack of... - Mazdutide: First Approval.
Drugs (2025) · ReviewMazdutide (Xinermei®) is a dual glucagon receptor (GcgR) and glucagon-like peptide-1 receptor (GLP-1R) agonist being developed by Eli Lilly and Company along with Innovent Biologics for use in weight...
6 Safety and risk profile
6.1 Regulatory status
Mazdutide is currently classified as Phase 3 clinical trials. It has no approved human indication in the United States; availability elsewhere does not imply demonstrated safety or efficacy.
Safety score: 68/100 — moderate concern. Derived from clinical data volume, known risks and regulatory status.
6.2 Contraindications
Conditions and populations in which use is contraindicated:
- Personal or family history of medullary thyroid carcinoma or MEN2
- History of pancreatitis
- Severe gastrointestinal motility disorder
- Pregnancy or lactation
- Type 1 diabetes mellitus
6.3 Drug interactions
| Drug or class | Interaction | Risk |
|---|---|---|
| Insulin / sulfonylureas | Additive glucose lowering from the GLP-1 component; monitor and reduce secretagogue dose. | High |
| Oral medications | Delayed gastric emptying alters absorption profile. | Moderate |
| Uricosurics / xanthine oxidase inhibitors | Additive urate lowering — monitor if used together. | Low |
6.4 Long-term risks
- Limited long-term data beyond 48–60 weeks
- Sustained heart-rate elevation of uncertain significance
- Unknown effects of chronic glucagon receptor agonism
- Weight regain on discontinuation
6.5 Research best practices
- Store lyophilised at −20 °C; reconstituted at 2–8 °C for short periods
- Escalate stepwise (typically 4-week intervals) to manage GI effects
- Monitor heart rate, hepatic panel and glycaemia
- Maintain protein intake and resistance loading during rapid weight loss
7 Frequently asked questions
- Is mazdutide approved anywhere?
- Yes — China's NMPA approved it for chronic weight management in June 2025 and for glycaemic control in type 2 diabetes in September 2025, marketed as Xinermei. It is not approved in the US or EU.
- What does the glucagon component add?
- Energy expenditure and hepatic effects. Trials showed reductions in liver fat, liver enzymes and serum uric acid alongside weight loss — signals characteristic of glucagon receptor agonism rather than GLP-1 activity alone.
- How does it compare to Western dual agonists?
- Its phase 3 data comes from Chinese populations at lower baseline BMI than Western obesity trials, so direct comparison with SURMOUNT or REDEFINE numbers is misleading. The 9 mg GLORY-2 data (up to 20.1%) is the most comparable figure to Western trial results.
8 References
- Novel GLP-1-based Medications for Type 2 Diabetes and Obesity. PubMed (2026). Son JW, et al.. View source
- Beyond weight loss: multisystem benefits of obesity medications. PubMed (2026). Savas M, et al.. View source
- Comparative effects of drugs for adults with overweight or obesity: systematic review and network meta-analysis. PubMed (2026). Nong K, et al.. View source
- Once-Weekly Mazdutide in Chinese Adults with Obesity or Overweight. PubMed (2025). Ji L, et al.. View source
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