# Mazdutide: Complete Research Profile — GLP-1/Glucagon Dual Agonist (2026)
Mazdutide (also known as IBI362 or LY3305677) has emerged as a landmark compound in the GLP-1/glucagon dual receptor agonist class. Developed by Innovent Biologics in partnership with Eli Lilly, mazdutide became the world's first approved GLP-1/glucagon dual receptor agonist when China's National Medical Products Administration (NMPA) approved it for weight management in June 2025, followed by glycemic control approval in September 2025. Its head-to-head superiority over semaglutide in the DREAMS-3 Phase 3 trial has made it one of the most discussed emerging peptides in metabolic disease research.
This profile covers mazdutide's mechanism of action, complete clinical trial data including the Phase 3 DREAMS program, its approval history, comparison to semaglutide and survodutide, and safety profile.
> Research Disclaimer: This article is for educational and informational purposes only. Mazdutide is approved in China but remains investigational in other regions. Content is based on published clinical research and does not constitute medical advice.
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What Is Mazdutide?
Mazdutide is a synthetic peptide analog of mammalian oxyntomodulin — a naturally occurring gut hormone that activates both the GLP-1 receptor (GLP-1R) and glucagon receptor (GCGR). Mazdutide is engineered for once-weekly subcutaneous administration with optimized receptor binding profiles for both targets.
Key identifiers:
- •Generic name: Mazdutide
- •Development codes: IBI362, LY3305677
- •Developed by: Innovent Biologics (with Eli Lilly partnership)
- •Mechanism: GLP-1R and GCGR dual agonist
- •Administration: Once-weekly subcutaneous injection
- •Research platform: 23 listings on Peptides.SO
Mazdutide's oxyntomodulin-based structure distinguishes it from other dual agonists like survodutide (glucagon-derived) and provides a native peptide framework for dual receptor engagement.
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Mechanism of Action
GLP-1 Receptor Agonism
Mazdutide's GLP-1 receptor activity drives:
- •Appetite suppression via central (hypothalamic) signaling
- •Slowed gastric emptying, reducing caloric absorption and post-meal glucose spikes
- •Glucose-dependent insulin secretion from pancreatic beta cells
- •Suppression of post-meal glucagon release from alpha cells
These effects produce the sustained caloric restriction and glycemic improvement characteristic of GLP-1 agonist class.
Glucagon Receptor Agonism
The glucagon receptor component adds:
Hepatic Metabolic Effects:
- •Activation of hepatic fatty acid beta-oxidation — burning fat stored in liver cells
- •Reduction of hepatic de novo lipogenesis — decreasing new fat synthesis from carbohydrates
- •Stimulation of hepatic lipoprotein processing, improving lipid profiles
- •Reduction of hepatic glycogen stores via glycogenolysis
Whole-Body Energy Effects:
- •Increases resting energy expenditure through thermogenic activation
- •Promotes lipolysis in adipose tissue, mobilizing stored fat for energy
- •Activates brown adipose tissue thermogenesis — a heat-generating pathway that burns calories without exercise
Balancing the Dual Agonism
A core pharmacological challenge is managing the counteracting effects: GLP-1R agonism reduces blood glucose while GCGR agonism raises it (via glycogenolysis and gluconeogenesis). Mazdutide's design achieves a favorable balance where the GLP-1 component prevents net hyperglycemia, while the glucagon component drives fat mobilization and energy expenditure. The net glycemic effect in metabolic disease is beneficial — more aggressive glucose and weight reduction than either mechanism alone.
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Preclinical Research
Preclinical studies demonstrated that mazdutide produced superior weight loss and metabolic improvements compared to GLP-1 monotherapy in animal models. The combination of energy restriction (GLP-1) and increased energy expenditure (glucagon) drove synergistic fat loss. Liver-specific effects were notable, with significant reductions in hepatic steatosis markers compared to GLP-1 monotherapy controls.
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Clinical Trial Program
Phase 1b — Dose Finding
An initial Phase 1b study in Chinese adults with overweight or obesity tested mazdutide at 9 mg and 10 mg doses. Mean changes from baseline showed meaningful weight reduction (up to −5.4%) at 12 weeks, establishing the safety and preliminary efficacy profile for higher doses in subsequent trials.
Phase 2 — Obesity Trial (Nature Communications, 2023)
A Phase 2 randomized controlled trial in Chinese overweight adults or adults with obesity tested mazdutide across multiple doses. Results demonstrated dose-dependent weight loss, establishing 6 mg as the primary Phase 3 dose for obesity.
Phase 2 — Type 2 Diabetes Trial (Diabetes Care, 2024)
In a randomized, double-blind, placebo-controlled Phase 2 trial in Chinese patients with type 2 diabetes:
HbA1c Changes (12-week study):
- •Mazdutide: reductions ranging from −1.46% to −2.23%
- •Body weight: reductions up to −5.4%
The combined glycemic and weight efficacy supported advancement to Phase 3.
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Phase 3 DREAMS Trial Program
The DREAMS (Diabetes and Obesity Research with Mazdutide) program is the most comprehensive clinical evidence for mazdutide.
DREAMS-1 (Monotherapy in T2D)
Evaluated mazdutide monotherapy vs. placebo in Chinese adults with type 2 diabetes over 24 weeks.
Results at Week 24:
| Treatment | HbA1c Reduction | Weight Reduction |
|---|---|---|
| Placebo | −0.14% | Minimal |
| Mazdutide 4 mg | −1.57% | Significant |
| Mazdutide 6 mg | −2.15% | Greater |
320 participants were randomized to once-weekly subcutaneous mazdutide (4 mg or 6 mg) or placebo. Both doses achieved statistically significant superiority over placebo on HbA1c and body weight outcomes.
DREAMS-2 (Add-on Therapy in T2D)
Evaluated mazdutide as add-on therapy to existing oral anti-diabetic drugs (OADs) in Chinese adults with type 2 diabetes. Mazdutide demonstrated superior glycemic control and body weight reduction versus placebo as an add-on treatment.
Two Phase 3 clinical results (DREAMS-1 and DREAMS-2) were published back-to-back in Nature in 2025, establishing mazdutide's efficacy across T2D treatment settings.
DREAMS-3 — Head-to-Head vs. Semaglutide
DREAMS-3 is the world's first Phase 3 head-to-head comparison of a GLP-1/glucagon dual receptor agonist against semaglutide, representing a landmark trial in the field.
Study Design:
- •349 Chinese adults with early-stage type 2 diabetes (duration <10 years) and obesity
- •Mazdutide 6 mg vs. semaglutide 1 mg, once weekly
- •32-week open-label, multicenter trial
- •Published: October 2025
Primary Endpoint: Proportion achieving HbA1c <7.0% AND ≥10% body weight reduction at Week 32
| Treatment | Composite Endpoint Achievement |
|---|---|
| Semaglutide 1 mg | 21.0% |
| Mazdutide 6 mg | 48.0% (p<0.0001) |
Mazdutide achieved the composite endpoint at more than twice the rate of semaglutide — a statistically and clinically significant superiority result.
Secondary Endpoints:
| Endpoint | Semaglutide | Mazdutide | p-value |
|---|---|---|---|
| HbA1c reduction | −1.84% | −2.03% | <0.05 |
| Body weight reduction | −6.00% | −10.29% | <0.05 |
Mazdutide produced 71% greater body weight reduction than semaglutide (10.29% vs. 6.00%) in this head-to-head comparison.
Safety in DREAMS-3:
- •Treatment-emergent adverse events (mainly GI): 62.6% (mazdutide) vs. 50.3% (semaglutide)
- •GI events were primarily mild-to-moderate and transient during dose escalation
- •Serious adverse events: 2.3% (mazdutide) vs. 1.7% (semaglutide) — not meaningfully different
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Regulatory History and Approvals
China NMPA Approvals (2025)
Mazdutide achieved two landmark regulatory approvals in China in 2025:
- •June 2025: NMPA approved mazdutide for weight management in adults with obesity or overweight with comorbidities — the first GLP-1/glucagon dual receptor agonist approved anywhere in the world for this indication.
- •September 2025: NMPA approved mazdutide for glycemic control in adults with type 2 diabetes.
These dual approvals make mazdutide the first-in-class approved GCG/GLP-1 dual receptor agonist globally.
Global Development Status
Mazdutide remains investigational outside of China. Innovent Biologics and Eli Lilly are continuing global clinical development, with ongoing trials in broader populations including non-Chinese patients. Phase 3 data from DREAMS-1 and DREAMS-2 published in Nature provide a strong regulatory package for future global submissions.
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Comparison to Other GLP-1/Metabolic Agents
| Feature | Mazdutide | Survodutide | Tirzepatide | Semaglutide |
|---|---|---|---|---|
| Receptor Targets | GLP-1 + Glucagon | GLP-1 + Glucagon | GIP + GLP-1 | GLP-1 only |
| Structural Basis | Oxyntomodulin | Glucagon | GIP analog | GLP-1 analog |
| Global Status | Approved (China); Ph3 globally | Phase 3 | Approved globally | Approved globally |
| Head-to-Head vs. Sema | Superior (DREAMS-3) | Not yet available | Superior (SURMOUNT-5) | Reference |
| Phase 3 Weight Loss | ~10.29% (vs. sema) | ~14.9% (Ph2, vs. placebo) | ~20.2% (vs. sema) | ~13.7% (STEP-1) |
| T2D Approval | Yes (China) | Investigational | Yes (globally) | Yes (globally) |
Important Context on Comparisons: Direct cross-trial comparisons are methodologically limited. The DREAMS-3 comparison used a 1 mg semaglutide dose (not the maximum 2.4 mg used in obesity trials). Tirzepatide's SURMOUNT-5 trial used 2.4 mg semaglutide. These differences make cross-study comparison of magnitude imprecise.
The key message: Mazdutide demonstrated clinically meaningful superiority over standard semaglutide dosing for T2D in head-to-head Phase 3 data — establishing it as a leading GLP-1/glucagon dual agonist in the class.
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Safety Profile
Class-Consistent GI Events:
As with all GLP-1 receptor agonists, the most common adverse events with mazdutide are gastrointestinal: nausea, diarrhea, vomiting, and decreased appetite. These events are predominantly:
- •Mild to moderate in severity
- •Concentrated during dose escalation periods
- •Transient, resolving with continued use in most cases
Phase 3 DREAMS Safety Summary:
- •DREAMS-3: 62.6% GI adverse events (mazdutide) vs. 50.3% (semaglutide) — higher but consistent with greater weight loss efficacy
- •Serious adverse events remained low (<3%) in both arms
- •No unexpected safety signals were reported across the DREAMS trial program
Research Considerations for Dual Agonism:
- •Glycemic monitoring is important given the counteracting GLP-1 (glucose-lowering) and glucagon (glucose-raising) effects
- •Heart rate: mild increases possible with glucagon receptor activation; monitoring is standard
- •Lipase elevations: monitored as with other GLP-1 agents; pancreatitis events were rare in trials
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Research Context
Mazdutide's approval in China and publication of Phase 3 data in Nature mark significant milestones for the GLP-1/glucagon dual agonist class. Key research themes:
Energy Expenditure Advantage: The glucagon receptor component theoretically provides superior fat oxidation vs. GLP-1 monotherapy. DREAMS-3's 71% greater weight loss vs. semaglutide in head-to-head data provides clinical validation of this mechanistic advantage.
Liver Fat and MASH Potential: The hepatic glucagon receptor effects that drive fat oxidation in the liver create rationale for mazdutide's investigation in fatty liver disease, a natural extension of the class's research.
Cognitive Effects: A 2025 study in eBioMedicine (The Lancet) demonstrated that mazdutide mitigated diabetes-associated cognitive dysfunction in preclinical models via multi-omics analysis, suggesting potential CNS research directions beyond metabolic endpoints.
Research procurement: Peptides.SO lists 23 vendors offering research-grade mazdutide. Use our peptide comparison tool and peptide calculator for research planning.
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Frequently Asked Questions
Q: What is mazdutide?
Mazdutide (IBI362/LY3305677) is a synthetic peptide analog of oxyntomodulin, acting as a once-weekly GLP-1 and glucagon receptor dual agonist. It is the world's first approved drug of its class, approved in China in 2025 for weight management and type 2 diabetes.
Q: How does mazdutide compare to semaglutide?
In the DREAMS-3 head-to-head Phase 3 trial, mazdutide 6 mg produced significantly greater weight loss (−10.29% vs. −6.00%) and HbA1c reduction (−2.03% vs. −1.84%) vs. semaglutide 1 mg over 32 weeks. The composite endpoint (HbA1c <7.0% + ≥10% weight loss) was achieved by 48% on mazdutide vs. 21% on semaglutide.
Q: Is mazdutide approved?
Mazdutide is approved in China for weight management (June 2025) and type 2 diabetes (September 2025). It remains investigational in the United States, Europe, and other global markets.
Q: How does mazdutide differ from survodutide?
Both are GLP-1/glucagon dual receptor agonists. Mazdutide is based on the natural oxyntomodulin peptide structure; survodutide is based on the glucagon peptide sequence. Mazdutide has active approvals (China) and head-to-head semaglutide data. Survodutide has strong MASH data and FDA Breakthrough Therapy Designation. Both are in Phase 3 globally.
Q: What doses of mazdutide are used in research?
Clinical trials have used doses of 4 mg and 6 mg once weekly, with 6 mg being the primary dose in Phase 3 trials and the approved dose for metabolic indications in China.
Q: What is the DREAMS trial program?
DREAMS (Diabetes and Obesity Research with Mazdutide) is Innovent Biologics' Phase 3 clinical trial program. DREAMS-1 and DREAMS-2 evaluated mazdutide vs. placebo in T2D; DREAMS-3 is the head-to-head trial vs. semaglutide. Results from DREAMS-1 and DREAMS-2 were published in Nature in 2025.
Q: What cognitive research is being done with mazdutide?
A 2025 study in eBioMedicine demonstrated that mazdutide mitigated diabetes-associated cognitive dysfunction in preclinical models via multi-omics pathway analysis, opening potential research directions in cognitive health associated with metabolic disease.
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Key Research References
1. Mazdutide versus placebo in Chinese adults with type 2 diabetes (DREAMS-1/2). Nature, 2025.
2. Innovent Mazdutide vs. Semaglutide Phase 3 DREAMS-3 results. PR Newswire, October 2025.
3. Mazdutide Phase 2 in Chinese adults with T2D. Diabetes Care, 2024.
4. Phase 2 RCT of mazdutide in Chinese overweight adults/adults with obesity. Nature Communications, 2023.
5. Mazdutide GCGR/GLP-1 dual agonist approval in China. GLP-1 Health, 2025.
6. Mazdutide mitigates diabetes-associated cognitive dysfunction00235-X/fulltext). eBioMedicine (The Lancet), 2025.
7. Mazdutide vs. semaglutide — head-to-head trial rationale, DREAMS-3. PubMed, 2025.
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Further Reading:
- •Survodutide: Complete Research Profile — Dual GLP-1/Glucagon Agonist (2026)
- •Cagrilintide: Complete Research Profile — Long-Acting Amylin Analog, CagriSema Trials & GLP-1 Comparison (2026)
- •GHK-Cu Peptide Research Guide: Anti-Aging Science, Applications, and Best Sources (2026)
- •PYY (Peptide YY): Complete Research Profile — The Gut Satiety Hormone in Appetite Regulation and Obesity Research (2026)
- •Peptide Stack Builder
- •Dosage Chart
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This article is for educational and research purposes only. Mazdutide is approved in China for specific indications; its regulatory status varies by country. This content does not constitute medical advice.