RESEARCH MONOGRAPH · KDC-MN-296

Mazdutide

May 9, 2026 Kodiac biolabs Research Revised May 30, 2026 2 min read

Our opinion on this compound

72/100

The most glucagon-weighted dual agonist in late-stage development, real efficacy with a more interesting mechanism balance than the GLP-1-heavy peers

Mazdutide (IBI362 / LY3305677) is the Innovent/Eli Lilly GLP-1/glucagon dual agonist thats genuinely interesting because of where the receptor activation ratio sits. Most of the duals (cotadutide especially) lean heavily GLP-1 with a small glucagon contribution. Mazdutide is closer to balanced, possibly even modestly glucagon-leaning at the higher doses, and that changes the metabolic phenotype.

The phase 2 and now phase 3 data in the China registrations are real. The GLORY-1 and DREAMS programs have shown sustained weight loss in the 14-18 percent range at higher doses over 48 weeks, with metabolic improvements (lipid profile, liver fat, blood pressure) that look meaningfully larger than the weight loss alone would predict. The hypothesis is that the glucagon arm contributes hepatic energy expenditure and lipid oxidation effects that you don't get from GLP-1 monotherapy.

What's interesting from a mechanism perspective is that mazdutide's regulatory pathway is China-first (NMPA review for obesity is moving), which is genuinely novel for this class. Lilly has the global rights but the development center of gravity has been Innovent and the Chinese trial population, which is a meaningfully different metabolic baseline than the US/European obesity trials and produces somewhat different efficacy reads.

What we like: balanced dual agonism, strong phase 2 and phase 3 efficacy data, and a mechanism story that genuinely differentiates from the GLP-1 monotherapy class. The MASH and liver fat data is among the better duals.

What we dont love is that the GcgR activation comes with metabolic costs that the marketing narrative doesnt always emphasize. Glucose homeostasis is more complex on a dual than on a pure GLP-1, the heart rate effects can be more pronounced, and the long-term safety in non-Chinese populations is still being characterized.

Sourcing for research-grade mazdutide is improving as the compound moves through phase 3. The peptide is well-characterized (Aib-substituted backbone, lipid sidechain for albumin binding) and HPLC plus mass spec QC is the standard. As with all duals, the receptor selectivity profile is the QC item that really matters and you can't verify that from peptide-level QC alone, you need cell-based assays.

Evidence: 75
Mechanism: 85
Reliability: 75
Safety: 65
Sourcing: 65
Value: 60
Signal: 75
Staying power: 78

Plain-language summary Intrigue 72 / 100

Mazdutide is a long-acting dual GLP-1 and glucagon receptor agonist developed by Eli Lilly and out-licensed to Innovent Biologics for development in China. Mechanistically similar to cotadutide and the natural peptide oxyntomodulin, but with a fatty-acid extension supporting rather than dosing. Phase 2 trials in Chinese type 2 diabetes and obesity populations showed dose-dependent weight loss and HbA1c reduction comparable to or exceeding semaglutide at higher dose tiers. Phase 3 trials are ongoing in China. It is shaping up to be the first dual GLP-1/glucagon agonist to reach a major market, beating its Western competitors. Not stocked by Kodiac. This monograph is provided for research and educational reference.

Intrigue 0–100 blends mechanism novelty, evidence strength, and translational potential. Kodiac editorial, not peer-reviewed.

GLP-1 / glucagon dual receptor agonist

A long-acting dual GLP-1 and glucagon receptor agonist; under development for obesity and type 2 diabetes.

Abstract

Mazdutide (IBI362, LY3305677; modified peptide with glucagon backbone and GLP-1 modifications; molecular weight approximately 4500 Da) is a dual GLP-1/glucagon receptor agonist developed by Eli Lilly and out-licensed to Innovent Biologics for development in China. The compound is structurally and mechanistically similar to cotadutide and oxyntomodulin, with C18 fatty acid extension for dosing. Phase 2 trials in type 2 diabetes and obesity demonstrated dose-dependent HbA1c reduction and weight loss comparable to or exceeding semaglutide at higher dose tiers. Phase 3 trials are ongoing in China (DREAMS program) and US. The dual mechanism produces increased energy expenditure (glucagon effect) on top of the GLP-1 appetite suppression. Used as a reference long-acting dual GLP-1/glucagon agonist.

Mechanism of action

Long-acting dual GLP-1 and glucagon receptor agonism with C18 fatty acid extension supporting dosing.

Reported research dose ranges

Investigational; phase 2 doses 1 to 9 mg subcutaneous.

References

Ji L, et al. Efficacy and safety of mazdutide once weekly in Chinese adults with obesity. Lancet Diabetes Endocrinol 2024.
Coskun T, et al. LY3305677 (mazdutide), a balanced GLP-1/glucagon receptor co-agonist. Diabetes 2021.
Liu C, et al. Mazdutide in obesity and metabolic disease. Expert Opin Investig Drugs 2024.

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KDC-MN-296

The full reference document is provided strictly for research use only. It reports research dose ranges from the published literature, not instructions for use in humans or animals.

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FOR RESEARCH USE ONLY. Not for medical, diagnostic, or therapeutic purposes. Not for human consumption. All information is provided for research and educational purposes only.

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Mazdutide

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References

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Abstract

Mechanism of action

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References

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