RESEARCH MONOGRAPH · KDC-MN-295

Cotadutide

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

Our opinion on this compound

64/100

AstraZeneca's GLP-1/glucagon dual that landed in development purgatory after MASH program reshuffling, mechanism still relevant

Cotadutide (MEDI0382) was AstraZeneca's contribution to the GLP-1/glucagon dual receptor agonist race, and the development trajectory tells you a lot about how this class has gotten reshuffled. Mechanism is the obvious one for the class: balanced agonism at both GLP-1R (for insulinotropic and satiety effects, the standard GLP-1 story) and GcgR (for hepatic energy expenditure and lipid oxidation, the glucagon-driven counterweight). The pitch is that you get more metabolic effect per percentage point of weight loss because you're activating both pathways.

The phase 2 data was real. PROXYMO and the MASH-focused phase 2 work showed meaningful liver fat reduction, weight loss in the 5-7 percent range over 6 months, and metabolic improvements that were modestly better than what GLP-1 monotherapy in the same population would predict. The MASH liver fat reduction (around 30-40 percent relative to baseline) was the more interesting signal.

What happened next is the messy part. AstraZeneca de-prioritized cotadutide as it pivoted resources toward AZD5004 (the oral GLP-1) and the broader portfolio reshuffle around the obesity space heating up. The compound didnt advance to phase 3 in obesity, and the MASH program got reframed multiple times. It's currently in a slow-roll development state that may or may not produce more data.

What we like: the mechanism is clean and the GLP-1/glucagon dual class is now well-validated by mazdutide and the retatrutide-adjacent compounds. Cotadutide as a research tool for studying balanced dual agonism is genuinely useful and the phase 2 data is the most we'll probably get for a while.

What we dont love is that the GcgR activation ratio in cotadutide is on the GLP-1-heavy end of the spectrum, which makes some of the differential pharmacology questions harder to interpret. The more glucagon-weighted analogs (mazdutide especially) are arguably better research tools for studying what the glucagon arm adds specifically.

Sourcing for research-grade cotadutide is limited but available. The peptide structure is well-characterized (Glu/Aib backbone modifications, fatty acid sidechain) and HPLC plus mass spec QC is mandatory. The Aib substitution is the typical class-defining modification.

Evidence: 60
Mechanism: 82
Reliability: 65
Safety: 65
Sourcing: 60
Value: 55
Signal: 65
Staying power: 60

Plain-language summary Intrigue 65 / 100

Cotadutide is a dual GLP-1 and glucagon receptor agonist from AstraZeneca, investigated for type 2 diabetes, fatty liver disease, and obesity. It is a balanced co-agonist (about 5:1 GLP-1 to glucagon). The GLP-1 component does the usual incretin work: insulin release, glucagon suppression, appetite reduction. The glucagon component independently raises energy expenditure and lipolysis, theoretically adding fat-burning on top of appetite suppression. Phase 2 trials showed strong glycemic and weight effects. AstraZeneca de-prioritized it in 2023 in favor of other pipeline assets, leaving its commercial future unclear. The dual-agonist concept lives on in mazdutide and survodutide. 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 dual GLP-1 and glucagon receptor agonist; investigated for type 2 diabetes, NASH, and obesity.

Abstract

Cotadutide (MEDI0382; CAS 2125247-22-1; modified peptide with glucagon backbone and GLP-1 modifications; approximately 30 amino acid peptide with C16 fatty acid extension; molecular weight approximately 4140 Da) is a dual GLP-1/glucagon receptor agonist developed at AstraZeneca for type 2 diabetes, non-alcoholic steatohepatitis (NASH), and obesity. The compound is a balanced co-agonist (approximately 5:1 GLP-1:glucagon ratio at receptor). The GLP-1 component drives glucose-dependent insulin secretion, glucagon suppression, and appetite reduction; the glucagon component independently increases hepatic fatty acid oxidation, energy expenditure, and lipolysis. Phase 2 trials demonstrated superior weight loss and HbA1c reduction compared to GLP-1 monoagonists at matched dose, with hepatic fat reduction supporting the NASH indication. Plasma half-life supports subcutaneous dosing; phase 3 development is ongoing. Used as a reference dual GLP-1/glucagon agonist in metabolic research.

Mechanism of action

Dual GLP-1 and glucagon receptor agonism (~5:1 GLP-1:glucagon ratio). Combines GLP-1 glucoregulatory and appetite effects with glucagon-mediated lipolysis and energy expenditure.

Reported research dose ranges

Investigational; phase 2 doses 100 to 600 mcg subcutaneous.

References

Ambery P, et al. MEDI0382, a GLP-1/glucagon receptor dual agonist, in obese or overweight patients with type 2 diabetes. Lancet 2018.
Parker VER, et al. Cotadutide in NASH: glucagon co-agonism rationale. Hepatology 2020.
Robertson D, et al. Pharmacokinetics and pharmacodynamics of cotadutide. Clin Pharmacokinet 2019.

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KDC-MN-295

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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Cotadutide

Abstract

Mechanism of action

Reported research dose ranges

References

Read the full monograph

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Abstract

Mechanism of action

Reported research dose ranges

References

Read the full monograph

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