Cotadutide

also known as: MEDI0382

AstraZeneca's discontinued GLP-1/glucagon dual agonist — shelved in 2023 despite positive Phase 2 data in NASH and obesity, reportedly for commercial rather than safety reasons. Included for pipeline completeness; the mechanism lives on in pemvidutide, survodutide, and the glucagon arm of retatrutide.

A balanced GLP-1/glucagon dual-agonist peptide developed by MedImmune and then AstraZeneca as MEDI0382, demonstrated in Phase 2 to produce weight loss and improve glycemia, liver fat, and MASLD biomarkers; AstraZeneca terminated the program in 2023 in favor of other pipeline priorities, but the pharmacological rationale was subsequently validated by pemvidutide (Altimmune), survodutide (Boehringer Ingelheim/Zealand), and the glucagon component of retatrutide (Eli Lilly).

Mechanism of action

Balanced agonism at the GLP-1 and glucagon receptors in a single peptide. GLP-1 agonism drives the canonical appetite-suppression, delayed-gastric-emptying, and glucose-dependent insulin secretion. Glucagon receptor co-agonism adds an energy-expenditure component — increased hepatic fatty acid oxidation, reduced hepatic steatosis, and modest thermogenic effects — while the GLP-1 arm counteracts the glucagon-driven tendency toward hyperglycemia. The same dual-agonist logic underlies pemvidutide and survodutide.

Primary uses

Historical: type 2 diabetes with chronic kidney disease (Phase 2 MERIT trial)
Historical: NASH/MASLD (Phase 2)
Historical: obesity (Phase 2)

Typical dosing

100–600 mcg once daily (subcutaneous)

Phase 2 protocols titrated from 100 mcg to 300–600 mcg once daily.

Regulatory status

Not approved. AstraZeneca announced discontinuation of cotadutide development in 2023. Prior to discontinuation, Phase 2b data in patients with type 2 diabetes and chronic kidney disease (MERIT trial) and separate Phase 2 data in NASH and obesity had been published; the discontinuation was attributed to pipeline prioritization rather than any safety signal.

References

[pubmed] Nahra R, et al. "Effects of cotadutide on metabolic and hepatic parameters in adults with overweight or obesity and type 2 diabetes: a 54-week randomized phase 2b study." Diabetes Care, 2021;44:1433-1442.
[pubmed] Boland ML, et al. "Resolution of NASH and hepatic fibrosis by the GLP-1R/GcgR dual-agonist cotadutide via modulating mitochondrial function and lipogenesis." Nat Metab, 2020;2:413-431.
[manufacturer] AstraZeneca plc. Pipeline update notice, 2023 (cotadutide discontinuation).

Related peptides

Pemvidutide

Altimmune's GLP-1 / glucagon co-agonist — received FDA Breakthrough Therapy Designation for MASH in January 2026 after positive IMPACT Phase 2b antifibrotic data, with Phase 3 initiation planned for 2026.

Survodutide

A once-weekly GLP-1/glucagon co-agonist in late-stage trials for obesity, type 2 diabetes, and MASH.

Retatrutide

An investigational triple hormone agonist that produced ~24% weight loss at 48 weeks in Phase 2 — the largest in any single-agent obesity trial to date.

Disclaimer

This entry is for educational purposes only and does not constitute medical advice. Dosing information reflects published regulatory or research data and is not a recommendation. Many compounds described here are not approved for human use in the United States. Consult a licensed medical professional before considering any peptide therapy.