Metabolic/Weight

Mazdutide

Research Reagent · Laboratory Use Only

Quick Answer

What do Phase 3 clinical trials show about mazdutide's efficacy for weight loss and diabetes?

Mazdutide (IBI362) is a once-weekly GLP-1/glucagon receptor dual agonist. The Phase 3 GLORY-1 trial (NEJM, June 2025) in 610 Chinese adults with overweight or obesity demonstrated 14.01% mean body weight reduction at 48 weeks with 6 mg versus 0.30% placebo. The Phase 3 GLORY-2 trial with 9 mg achieved up to 20.1% weight loss. Mazdutide received approval from China's NMPA and is the first Chinese-developed GLP-1/GCGR dual agonist to complete Phase 3 registration trials.

PMID38092790↗DOI10.1038/s41467-023-44067-4↗⟳ Reconstitution Calculator
Scientific AbstractPMID 38092790 · 2023

Background

Mazdutide (IBI362) is a once-weekly glucagon-like peptide-1 (GLP-1) and glucagon receptor (GCGR) dual agonist developed by Innovent Biologics in collaboration with Eli Lilly. This interim analysis of a randomised, double-blind, placebo-controlled Phase 2 trial enrolled 248 Chinese overweight or obese adults (BMI ≥24 kg/m² with comorbidities or BMI ≥28 kg/m²) randomly assigned to once-weekly mazdutide 3 mg, 4.5 mg, 6 mg, or placebo for 24 weeks.

Results

Mean body weight changes from baseline at week 24 were −6.7%, −10.4%, and −11.3% at 3, 4.5, and 6 mg respectively versus +1.0% with placebo (treatment differences −7.7% to −12.3%, all p<0.0001). PHASE 3 GLORY-1 (NCT05607680; NEJM 2025, DOI 10.1056/NEJMoa2411528): 610 participants randomised to mazdutide 4 mg, 6 mg, or placebo for 48 weeks; mean body weight reduction −11.00% (4 mg) and −14.01% (6 mg) vs +0.30% placebo. Phase 3 GLORY-2 (NCT06164873): mazdutide 9 mg achieved up to 20.1% weight loss. Phase 3 DREAMS-3 comparing mazdutide vs semaglutide in T2D with obesity is also ongoing. Mazdutide has been approved in China and is the first Chinese-developed GLP-1/GCGR dual agonist to complete Phase 3 global registration trials.

Source:10.1038/s41467-023-44067-4
Mechanistic Research SummaryCurated from PubMed

This data is for laboratory research purposes only. Not for human or animal consumption.

What is Mazdutide?

Mazdutide (IBI362, also known as OXM3) is an investigational once-weekly GLP-1 receptor and glucagon receptor (GCGR) dual agonist developed by Innovent Biologics in collaboration with Eli Lilly. It is structurally based on a modified oxyntomodulin sequence with a C18 fatty acid chain for half-life extension. Mazdutide has completed Phase 3 trials in China and received approval from China's National Medical Products Administration (NMPA) for type 2 diabetes and obesity management.

Mechanism of Action

Mazdutide is a 30-amino acid acylated peptide that activates both the GLP-1 receptor (GLP-1R) and the glucagon receptor (GCGR) with balanced dual agonism. The GLP-1R component mediates satiety, slows gastric emptying, and enhances glucose-dependent insulin secretion. The GCGR component drives thermogenesis, hepatic fatty acid oxidation, and direct lipolysis — effects that are complementary to GLP-1R agonism and contribute to superior hepatic fat reduction compared to pure GLP-1 agonists.

Observed Laboratory Results

  • Phase 3 GLORY-1 (NCT05607680, NEJM June 2025): −11.00% body weight (4 mg) and −14.01% body weight (6 mg) vs +0.30% placebo at 48 weeks; liver fat content reduced by up to 80.2%.
  • Phase 3 GLORY-2 (NCT06164873): Mazdutide 9 mg achieved up to 20.1% weight loss in Chinese adults with obesity (BMI ≥30 kg/m²).
  • Phase 2 (NCT04904913): −11.3% body weight at 24 weeks with 6 mg vs +1.0% placebo.
  • Glycemic control: Phase 3 DREAMS-1 and DREAMS-2 in type 2 diabetes demonstrated significant HbA1c reductions published back-to-back in Nature (2025).
  • Safety: GI adverse events (nausea, diarrhoea, vomiting) are the most common, predominantly mild-to-moderate and transient.

Regulatory Status

  • NMPA (China) approval for type 2 diabetes and obesity management
  • Phase 3 DREAMS-3 head-to-head vs semaglutide ongoing
  • Global development with Eli Lilly collaboration under evaluation
Clinical Research Parameters
3 trials2 human studies

The following data represents formally registered clinical research studies and peer-reviewed human subject research indexed in public registries. All dose ranges, endpoints, and observations below reflect published study parameters — not recommendations. For research reference only.

Registered Clinical Trials
ClinicalTrials.gov ↗
NCT05607680 ↗
COMPLETEDPhase IIIn=610

A Phase 3 Study to Evaluate the Efficacy and Safety of Mazdutide in Chinese Adults With Overweight or Obesity (GLORY-1)

GLORY-1 is a Phase 3, randomised, double-blind, placebo-controlled trial evaluating once-weekly subcutaneous mazdutide 4 mg and 6 mg versus placebo in 610 Chinese adults with obesity (BMI ≥28 kg/m²) or overweight (BMI 24–<28 kg/m²) with at least one weight-related comorbidity for 48 weeks. Results published in the New England Journal of Medicine (June 2025, DOI 10.1056/NEJMoa2411528): mean body weight change at week 48 was −11.00% (4 mg), −14.01% (6 mg), and +0.30% placebo. Participants achieving ≥15% weight loss: 35.7% (4 mg), 49.5% (6 mg), 2.0% placebo. Liver fat content reduced by up to 80.2% in participants with high baseline fat. GLORY-1 is the first Phase 3 study of a Chinese-developed innovative metabolic drug published in the NEJM.

Study Interventions
Mazdutide 4 mg, Mazdutide 6 mg, Placebo
Primary Endpoints
Percentage change in body weight from baseline at week 32; Proportion of participants with ≥5% body weight reduction at week 32
Study Period
2022-11 → 2024-04
NCT06164873 ↗
COMPLETEDPhase IIIn=440

A Phase 3 Study to Evaluate the Efficacy and Safety of Mazdutide 9 mg in Chinese Adults With Obesity (GLORY-2)

GLORY-2 evaluated mazdutide 9 mg versus placebo in Chinese adults with obesity (BMI ≥30 kg/m²) with lifestyle intervention. Top-line results announced 2025: mazdutide 9 mg achieved up to 20.1% mean body weight reduction, meeting all primary and key secondary endpoints. This extends the efficacy profile of mazdutide to higher-dose regimens comparable to advanced dual and triple agonists.

Study Interventions
Mazdutide 9 mg, Placebo
Primary Endpoints
Percentage change in body weight from baseline; Proportion achieving ≥5% weight loss
Study Period
2023-06 → 2025-03
NCT04904913 ↗
COMPLETEDPhase IIn=248

A Phase 2 Randomised Study of Mazdutide (IBI362) in Chinese Overweight or Obese Adults

Phase 2, double-blind, placebo-controlled trial in 248 Chinese adults with overweight (BMI ≥24 with comorbidity) or obesity (BMI ≥28) randomised to mazdutide 3 mg, 4.5 mg, 6 mg, or placebo once weekly for 24 weeks. Mean body weight changes: −6.7%, −10.4%, −11.3% vs +1.0% placebo (all p<0.0001). Dose-dependent weight loss confirmed. Published in Nature Communications (December 2023).

Study Interventions
Mazdutide 3 mg, Mazdutide 4.5 mg, Mazdutide 6 mg, Placebo
Primary Endpoints
Percentage change from baseline in body weight at week 24
Study Period
2021-04 → 2022-09
Research Compliance Notice

All data presented on this page is for laboratory research purposes only. Mazdutide is referenced here as a research reagent. This page does not constitute medical advice, clinical guidance, or endorsement of any compound for human or animal use. All referenced studies are available via PubMed (PMID: 38092790) and the DOI-linked journal publication. Researchers must consult applicable institutional and regulatory frameworks before conducting any protocols.

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