Mazdutide: Research Overview

Mazdutide (IBI362) is a once-weekly subcutaneous glucagon-like peptide-1 (GLP-1) and glucagon receptor (GCGR) dual agonist developed by Innovent Biologics, with Eli Lilly holding rights outside of China. In June 2025, China's National Medical Products Administration (NMPA) approved mazdutide as the world's first approved GCG/GLP-1 dual receptor agonist for chronic weight management in Chinese adults with overweight or obesity. A supplemental application for a higher 9 mg dose in moderate-to-severe obesity was accepted for NMPA review in 2025. Mazdutide does not have regulatory approval in the United States or Europe as of May 2026; global phase 3 development is ongoing.

What is Mazdutide?

Mazdutide is a synthetic peptide analogue designed to act as a balanced co-agonist at both the GLP-1 receptor and the glucagon receptor. Eli Lilly originally synthesised the compound; Innovent Biologics secured a licence for the Chinese market in 2019. It is formulated for once-weekly subcutaneous injection. In China, it was approved for chronic weight management in June 2025, and a second NMPA approval for glycaemic control in adults with type 2 diabetes followed in September 2025, making mazdutide the first dual GCG/GLP-1 agonist approved for both indications in any country.

Outside China, Eli Lilly retains global development rights. Phase 3 development for the US and international markets had not reached a regulatory filing as of May 2026. The MUSE trial program evaluates mazdutide in type 2 diabetes in Chinese adults and has reported phase 3 data published in Nature.

Mechanism of Action

Mazdutide simultaneously activates two distinct GPCRs: the GLP-1 receptor and the glucagon receptor. GLP-1 receptor agonism on pancreatic beta cells amplifies glucose-dependent insulin secretion, suppresses glucagon, slows gastric emptying, and promotes central satiety. These are the same pathways engaged by approved GLP-1 receptor agonists such as semaglutide or dulaglutide.

The additional glucagon receptor agonism is the distinguishing feature of mazdutide and the broader GLP-1/GCGR dual agonist class. Glucagon receptor activation in adipose tissue and the liver stimulates lipolysis and hepatic fatty acid oxidation, increasing energy expenditure. In the liver, GCGR agonism promotes fatty acid oxidation and can reduce hepatic lipid content — an effect of interest for MASH (metabolic dysfunction-associated steatohepatitis). The net result is a greater thermogenic and lipolytic effect than GLP-1 receptor agonism alone, potentially enabling larger weight loss at equivalent tolerability.

What the Research Shows

The pivotal phase 3 GLORY-1 trial randomised 610 Chinese adults with obesity (BMI ≥28) or overweight (BMI 24–28 with a comorbidity) to once-weekly mazdutide 4 mg, 6 mg, or placebo for 48 weeks. Results were published in the New England Journal of Medicine in May 2025 (DOI: 10.1056/NEJMoa2411528; PMID 40421736). At week 48, the mean percentage change in body weight was −11.00% in the 4 mg group, −14.01% in the 6 mg group, and +0.30% in the placebo group. Approximately 74% of patients on 4 mg and 83% on 6 mg achieved at least 5% weight loss versus 11.5% on placebo. Discontinuation due to adverse events was low and comparable across groups (~1%).

A higher-dose extension, GLORY-2, evaluated mazdutide 9 mg in Chinese adults with moderate to severe obesity and reported mean weight loss of up to 20.1% from baseline at the primary endpoint, meeting all primary and key secondary endpoints. The GLORY-2 data supported the supplemental NMPA application for the 9 mg dose.

The MUSE phase 3 program evaluated mazdutide in Chinese adults with type 2 diabetes. Two phase 3 MUSE trials were published back-to-back in Nature (announced 2025), demonstrating significant HbA1c reductions and weight loss compared with placebo or active comparators in the Chinese T2D population. These data supported the September 2025 NMPA approval for glycaemic control.

Safety data across the GLORY and MUSE programs were consistent with the GLP-1 receptor agonist class: the most common adverse events were gastrointestinal (nausea, vomiting, diarrhoea), primarily mild to moderate and occurring early in treatment. No novel safety signals specific to the GCGR agonism component were identified in phase 3.

Pharmacokinetics

Mazdutide is formulated for once-weekly subcutaneous injection, consistent with a half-life sufficient to maintain therapeutic concentrations across a 7-day dosing interval. Phase 2 pharmacokinetic data in Chinese adults support steady-state accumulation within approximately 4 weeks of weekly dosing. Detailed published PK parameters from the phase 3 program in English-language literature were not yet fully available as of the time of this guide's preparation; the FDA label (once available) will be the authoritative source for Western-population PK data. Clearance is primarily through proteolytic catabolism.

Common Research Dose Ranges

Not medical advice. These are ranges reported in research literature, not personalized recommendations. Consult your physician.

Phase 3 GLORY-1 used 4 mg and 6 mg once-weekly doses as the primary dose range for obesity. The GLORY-2 extension examined 9 mg once weekly for moderate to severe obesity. The MUSE program examined doses relevant to T2D glycaemic control. All doses in the GLORY and MUSE programs were administered subcutaneously once weekly. Mazdutide is not approved in the US; dose ranges cited here reflect Chinese pivotal trial data.

Storage and Handling

Specific storage conditions for the approved Chinese formulation follow standard requirements for protein-based injectables: refrigeration at 2–8°C (36–46°F), protection from light and freezing. Storage conditions for any future US formulation will be specified in the FDA-approved prescribing information at the time of approval. As mazdutide is not currently available as an approved product outside China, handling guidance is only available from Chinese labelling.

What It Is NOT

Mazdutide is not tirzepatide (Mounjaro/Zepbound), which is a GLP-1/GIP dual agonist from Eli Lilly that targets a different receptor pair (GLP-1R and GIPR rather than GLP-1R and GCGR). It is not survodutide (BI 456906), a competing GLP-1/glucagon dual agonist from Boehringer Ingelheim/Zealand that is in phase 3 globally but remains unapproved as of May 2026. It is not retatrutide (LY3437943), a triple agonist targeting GLP-1R, GIPR, and GCGR simultaneously. Mazdutide is not approved by the FDA or EMA and is not available through standard pharmaceutical channels outside China.

References

Key citations include the GLORY-1 publication in NEJM (PMID 40421736), the Innovent NMPA approval press release (June 2025), GLORY-2 top-line results, and the MUSE program Nature publications. Regulatory status was verified via web search in May 2026.