Mazdutide
Also known as: IBI362, LY3305677, OXM3, Xinermei, GCG/GLP-1 dual receptor agonist, Oxyntomodulin analogue
Overview
Mazdutide (IBI362, marketed as Xinermei in China) is the world's first approved dual glucagon (GCG)/GLP-1 receptor agonist, developed by Innovent Biologics under an exclusive license from Eli Lilly. It is a mammalian oxyntomodulin (OXM) analogue — a naturally occurring gut hormone that activates both GLP-1 and glucagon receptors — modified with a fatty acid side chain for once-weekly subcutaneous dosing and extended half-life. China's National Medical Products Administration (NMPA) approved mazdutide for chronic weight management in June 2025 (GLORY-1 Phase 3 trial results published in NEJM) and for type 2 diabetes glycemic control in September 2025 (DREAMS-1 and DREAMS-2 results published back-to-back in Nature). Mazdutide is the only GLP-1-based therapy to achieve top-tier publications in both Nature and NEJM. Its Phase 3 GLORY-1 weight loss data showed up to 15.4% treatment difference vs. placebo at 24 weeks (9 mg dose). In the DREAMS-3 head-to-head trial, mazdutide outperformed semaglutide in both HbA1c reduction and weight loss.
Mechanism of Action
Dual GCG/GLP-1 receptor agonism based on a modified oxyntomodulin scaffold: GLP-1R activation suppresses appetite, enhances insulin secretion, and reduces postprandial glucose; GCGR activation drives hepatic fatty acid oxidation, thermogenesis, and liver fat reduction. Both receptors independently contribute to weight loss and metabolic improvement. Fatty acid side chain enables once-weekly dosing through albumin binding.
Potential Benefits
- China NMPA approved June 2025 for obesity/overweight (GLORY-1); first-in-class approval
- China NMPA approved September 2025 for T2D glycemic control (DREAMS-1, DREAMS-2)
- GLORY-1 (Phase 3, obesity): -15.4% body weight vs. placebo at 24 weeks (9 mg group)
- DREAMS-1 (Phase 3, T2D monotherapy): HbA1c -2.15% and body weight -7.81% (6 mg, 24 weeks)
- DREAMS-2 (Phase 3, T2D add-on): superior to dulaglutide 1.5 mg in HbA1c and weight
- DREAMS-3 (Phase 3 head-to-head): superior to semaglutide in HbA1c <7% and ≥10% weight loss
- Phase 2 (9 mg, obesity): 15.4% weight difference vs. placebo at 24 weeks — approaching bariatric surgery
- GLORY-1 published in NEJM; DREAMS-1 and DREAMS-2 published in Nature (back-to-back)
- Reductions in waist circumference, triglycerides, LDL, blood pressure, uric acid, liver enzymes, liver fat
- Multiple China Phase 3 trials: GLORY-1,2,3, GLORY-OSA, DREAMS-1,2,3, pediatric and MASH studies
Research Dosage Notes
The following reflects doses used in published research studies. This is not medical advice.
Consult published research literature for study-specific protocols.
Routes of Administration
Subcutaneous Injection High
Once-weekly SC injection; approved in China at 4 mg and 6 mg. Slow absorption with Tmax ~72 hours (range 12–170 hours in Phase 1b); long half-life 7–45 days depending on dose. Injection sites: abdomen, thigh.
Read our full Routes of Administration Guide for detailed comparison of all delivery methods.
Stacking Protocols
Popular research stacks involving Mazdutide:
Metabolic Health Stack
Combines Mazdutide with MOTS-c (mitochondrial metabolism) and AOD-9604 (lipolysis) for metabolic optimization.
Explore our complete Peptide Stacking Guide for more combinations and safety considerations.
Reconstitution
| Storage | Refrigerate at 2-8°C after reconstitution. Do not freeze reconstituted solution. |
|---|
Typical vial sizes: 5 mg. Add bac water slowly down the side of the vial, swirl gently — do not shake. Use insulin syringe for precise dosing.
Need exact syringe measurements?
Amino Acid Sequence
Mammalian oxyntomodulin (37 AA) analogue with fatty acid side chain attached for albumin binding and extended half-life; exact sequence proprietary to Innovent/Lilly
Side Effects & Safety
- Nausea (most common; dose-dependent, typically mild to moderate)
- Vomiting
- Diarrhea
- Constipation
- Decreased appetite (intended effect)
- Mild hypoglycemia possible (1 case at 9 mg in Phase 1b; monitor in T2D patients with insulin)
- No serious adverse events in Phase 1b or Phase 2/3 trials
- No discontinuations due to adverse events at approved doses in Phase 1b
- Safety profile consistent with other GLP-1 receptor agonist class drugs
Safety & Contraindications
This information is for educational purposes only. Consult a qualified healthcare provider before using any peptide.
MTC/MEN2
GLP-1 receptor agonist component. Contraindicated in patients with personal or family history of MTC or MEN2.
Pancreatitis History
Cases of acute pancreatitis reported in clinical trials. Discontinue if pancreatitis is suspected.
Severe Renal Impairment
Limited data in eGFR <15 mL/min. Dose adjustment may be needed.
Pregnancy & Lactation
Not studied. Contraindicated in pregnancy.
Drug Interactions
- Insulin/sulfonylureas: Increased risk of hypoglycemia. Reduce insulin dose when initiating mazdutide.
- Oral medications: May delay gastric emptying and affect absorption of oral drugs.
FDA Safety Information
Approved in China (NMPA) June 2025 for T2DM, September 2025 for obesity. Not yet approved by FDA or EMA.
Pharmacokinetics
| Half-Life | ~7 days (typical for once-weekly dosing; Phase 1b range: 7.3–44.8 days depending on dose) |
|---|---|
| Storage | Refrigerate at 2–8°C; do not freeze; protect from light; standard GLP-1 analog storage |
Synergistic Compounds
The following compounds have been studied alongside Mazdutide for potential complementary or synergistic effects:
Learn More
References & Further Reading
- Innovent announces mazdutide approved by China's NMPA for chronic weight management
- Innovent announces mazdutide received NMPA approval for glycemic control in T2D
- Nature: Two Phase 3 Clinical Results of Mazdutide in Chinese adults with T2D published back-to-back
- A phase 2 randomised controlled trial of mazdutide in Chinese overweight/obese adults
- Safety and efficacy of mazdutide (IBI362) 9 mg and 10 mg in Chinese adults with overweight or obesity — Phase 1b trial