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approvedWeight Loss & Diabetes

Mazdutide

Also known as: LY3305677, IBI362

Mazdutide is a once-weekly injectable dual GLP-1/glucagon receptor agonist co-developed by Eli Lilly and Innovent Biologics for obesity and type 2 diabetes. It activates both GLP-1 receptors (appetite suppression, insulin secretion) and glucagon receptors (increased energy expenditure, hepatic lipid mobilization). Phase 3 trials in China (GLORY program) demonstrated up to 14–18% weight loss at 48 weeks, leading to regulatory approval in China in 2024.

4 cited references·5 researched benefits

Quick Answer

Mazdutide is a once-weekly dual GLP-1/glucagon receptor agonist developed by Innovent Biologics and Eli Lilly. By combining GLP-1 appetite suppression with glucagon receptor-mediated energy expenditure increase, it offers a differentiated mechanism from GIP/GLP-1 agents like tirzepatide. Phase 3 GLORY trials showed 14–18% body weight loss at 48 weeks. Approved in China in 2024 for obesity, it represents the glucagon-inclusive approach to next-generation metabolic therapeutics.

Key Facts

Mechanism
Mazdutide is an acylated peptide that co-agonizes both GLP-1 and glucagon receptors with balanced potency. GLP-1 receptor activation drives appetite suppression through hypothalamic satiety signaling, glucose-dependent insulin secretion, and delayed gastric emptying. Glucagon receptor activation increases hepatic glycogenolysis and gluconeogenesis, but more importantly stimulates energy expenditure through thermogenesis, enhances hepatic lipid oxidation (reducing liver fat), and promotes lipolysis in adipose tissue. The glucagon component's hyperglycemic tendency is offset by the GLP-1 component's insulin-stimulating and glucagon-suppressing effects, maintaining glycemic balance while providing the metabolic benefits of both pathways.
Research Status
approved
Half-Life
~5–6 days
Primary Use
Weight Loss & Diabetes
Table of Contents

Benefits

  • Significant weight loss — 14–18% body weight reduction in phase 3 GLORY trials at 48 weeksstrong
  • Dual receptor mechanism — glucagon co-agonism increases energy expenditure beyond what GLP-1 alone achievesstrong
  • Liver fat reduction — glucagon receptor activation promotes hepatic lipid oxidation, potentially beneficial for MASLD/MASHmoderate
  • Glycemic improvement — significant HbA1c reductions in patients with type 2 diabetesstrong
  • Lipid profile improvement — reductions in triglycerides and improvements in cholesterol parametersmoderate

Dosage Protocols

RouteDosage RangeFrequencyNotes
Subcutaneous injection3–9 mg (target dose)Once weeklyDose escalation from 3 mg weekly, increasing every 4 weeks through 4.5 mg and 6 mg to the target dose of 9 mg. Administered on the same day each week.

Medical disclaimer

Dosage information is provided for educational reference only. Always follow your prescriber's instructions and consult a qualified healthcare provider before starting any peptide protocol.

Side Effects

  • Nausea — most common adverse event (30–40%), typically during dose titration and diminishing over timecommon
  • Diarrhea — gastrointestinal effects in 10–20% of patientscommon
  • Vomiting — reported in 10–15% during dose escalationcommon
  • Heart rate increase — modest elevation (2–5 bpm) observed in clinical trials, consistent with GLP-1 RA class effectrare
  • Transient hyperglycemia — possible during glucagon receptor activation, generally offset by GLP-1 componentrare

Frequently Asked Questions

How does mazdutide differ from tirzepatide?
Mazdutide targets GLP-1 + glucagon receptors, while tirzepatide targets GLP-1 + GIP receptors. These are fundamentally different dual-agonist strategies. Tirzepatide's GIP component may enhance insulin sensitivity and fat storage capacity, while mazdutide's glucagon component increases energy expenditure and hepatic lipid oxidation. Both achieve significant weight loss (15–25%), but through partially different mechanisms. Direct head-to-head trials have not been conducted.
Why add glucagon agonism to a GLP-1 RA?
While glucagon raises blood glucose, it also provides metabolic benefits often overlooked: increased basal metabolic rate through thermogenesis, enhanced liver fat oxidation (relevant for MASLD/MASH), and promotion of adipose tissue lipolysis. The GLP-1 component counteracts glucagon's hyperglycemic effect through insulin stimulation, creating a net neutral or positive glycemic impact while harnessing glucagon's energy expenditure benefits. This strategy may produce more weight loss than GLP-1 alone by increasing calories burned rather than just reducing calories consumed.
Is mazdutide available outside of China?
As of early 2026, mazdutide is approved and marketed only in China by Innovent Biologics. Eli Lilly holds ex-China rights but has not announced a timeline for regulatory submissions in the US or EU. Development outside China may depend on Eli Lilly's strategic prioritization alongside tirzepatide, which is already approved globally. International availability is uncertain.
What were the GLORY trial results?
The GLORY phase 3 program evaluated mazdutide in Chinese patients with obesity and/or type 2 diabetes. GLORY-1 (obesity without diabetes) demonstrated approximately 14–18% weight loss at 48 weeks across dose groups. GLORY-2 (obesity with T2D) showed significant weight loss and HbA1c reductions. These results supported China NMPA approval in 2024, making mazdutide one of the first GLP-1/glucagon dual agonists to reach market.
How does mazdutide compare to survodutide?
Both mazdutide and survodutide (developed by Boehringer Ingelheim) are GLP-1/glucagon dual receptor agonists with similar mechanisms. Survodutide showed up to 18.7% weight loss in phase 2 MASH trials and is in phase 3 globally. Mazdutide achieved approval first (China, 2024) but with a more limited geographic scope. Both validate the GLP-1/glucagon dual-agonist approach. Direct comparison requires head-to-head trials that have not been conducted.

References

  1. 1
    Safety, tolerability, pharmacokinetics, and pharmacodynamics of mazdutide (IBI362) in Chinese patients with type 2 diabetes(2023)PubMed ↗
  2. 2
    Glucagon/GLP-1 receptor dual agonism for obesity: rationale, mechanisms, and clinical progress(2022)PubMed ↗
  3. 3
    Glucagon receptor signaling and its metabolic effects: a review(2021)PubMed ↗
  4. 4
    Dual GLP-1/glucagon agonists: the emerging landscape of incretin-based therapeutics(2022)PubMed ↗

Latest Research

Last updated: 2026-02-19