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Evidence: MediumPeptideDiscontinuedGLP-1 and glucagon dual agonistDiscontinued in 2023Diabetes, kidney and liver disease

Cotadutide

A once-daily dual agonist that reached phase 2b in diabetes, kidney and liver disease before AstraZeneca shelved it

Cotadutide activates the GLP-1 and the glucagon receptor in one peptide. Its trials lowered blood sugar, weight, urinary albumin and liver fat, but AstraZeneca stopped development in 2023 for portfolio reasons, not on a safety finding.

View Dosing Data Read Research →
Overview

What is it?

Most incretin drugs act at one receptor. Cotadutide, first called MEDI0382, acts at two: the GLP-1 receptor, which slows the stomach and lowers blood sugar, and the glucagon receptor, which raises energy expenditure and pushes the liver to burn fat. Glucagon raises blood sugar, so balancing the two was the design problem.

In 51 people with type 2 diabetes the glucose rise after a test meal fell 23 percentage points more than on placebo. In 834 adults treated for 54 weeks, HbA1c and weight fell against placebo, and 300 µg improved liver enzymes and fibrosis scores where liraglutide did not.

That pushed the work towards the kidney and the liver. In 248 people with diabetic kidney disease it cut urinary albumin by about half on top of standard care; in 74 with biopsy-proven MASH, 600 µg improved liver fat and enzymes, with side effects in nine of ten.

Pooled, the trials show a modest drug. Across nine trials in 1,525 people with type 2 diabetes, HbA1c fell about 0.7 points against placebo at every dose, while weight loss rose with dose to 5.5% at 600 µg. A mechanistic study gave the clearest evidence of its glucagon side: it lowered liver glycogen and fat more than liraglutide did.

The trials also mapped its dosing. Its half-life is about 13 hours, so it was injected daily, and modelling suggested doubling the dose every two weeks to keep nausea near 25% at 600 µg. A depot formulation reported in 2025 stretched the half-life to 100 hours in rats; AstraZeneca had already discontinued the daily formulation in 2023, without a completed phase 3.

−5.5%
Weight at 600 µg
pooled vs placebo, type 2 diabetes
~50%
Lower urinary albumin
diabetic kidney disease, phase 2b
13.3 h
Half-life
hence daily injections
Science

Mechanism of Action

Cotadutide is a once-daily injected peptide that activates both the GLP-1 receptor and the glucagon receptor.

🍬

GLP-1 receptor

Lowers post-meal glucose and HbA1c and slows the stomach, as other GLP-1 drugs do.

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Glucagon receptor in the liver

Reduced liver glycogen and fat more than liraglutide, the signature of glucagon receptor engagement.

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Kidney

Cut urinary albumin by about half in diabetic kidney disease, an effect linked to exposure in modelling.

Evidence

Published Research

These are the trials that describe cotadutide, read from their PubMed abstracts: first-in-human, two in type 2 diabetes, one in kidney disease and one in liver disease.

Human2018

First in humans

Thirty-six healthy adults took a single injection of 5 to 300 µg and twelve took placebo. Adverse events were mild or moderate and clustered at 150 µg and above; the half-life was 9.5 to 12.1 hours.

PMID: 29926478
Human2018

Phase 2a in type 2 diabetes

51 adults with type 2 diabetes took up to 200 µg daily or placebo for up to 41 days. The glucose rise after a test meal fell 32.8% against 10.2% on placebo.

PMID: 29945727
Human2021

The 54-week phase 2b

834 adults on metformin took 100, 200 or 300 µg, placebo or open-label liraglutide. HbA1c and weight fell against placebo at 14 and 54 weeks; at 300 µg liver enzymes and two fibrosis scores improved where liraglutide did not.

PMID: 34016612
Human2024

Phase 2b in diabetic kidney disease

248 people with type 2 diabetes and chronic kidney disease took 100, 300 or 600 µg or placebo for 26 weeks on top of standard care. Urinary albumin fell 43.9% at 300 µg and 49.9% at 600 µg.

PMID: 39218393
Human2024

PROXYMO, in biopsy-proven MASH

74 people with biopsy-confirmed MASH took 600 µg, 300 µg or placebo for 19 weeks. At 600 µg liver fat fell 5.0 points more than placebo, with side effects in 91.7% against 37.5% and 16.7% stopping.

PMID: 38729399
Human2023

Liver glycogen and fat

In people with overweight or obesity and type 2 diabetes, cotadutide reduced liver glycogen and liver fat more than placebo and liraglutide, evidence that it engages the glucagon receptor in the human liver.

PMID: 38066113
Human2023

600 µg in Japanese patients

In 16 Japanese patients with type 2 diabetes and BMI 25 or higher, cotadutide improved 7-day mean glucose on continuous monitoring; 11 of 12 had a side effect, mostly mild and gastrointestinal, with no serious events.

PMID: 37337366
Human2023

Kidney impairment does not change exposure

In a single-dose phase 1 study of 37 people, cotadutide exposure was similar in severe or moderate renal impairment and normal kidney function.

PMID: 37140727
Human2024

Population pharmacokinetics

A model across trials estimated a half-life of 13.3 hours, with body weight, liver enzymes, albumin and anti-drug antibodies among the factors affecting exposure; antibodies reduced clearance.

PMID: 38236561
Human2025

Modelling the kidney effect

Exposure-response modelling of the kidney trial predicted that 26 weeks of 600 µg would cut urinary albumin-to-creatinine ratio by about 46% and body weight by about 5% against placebo.

PMID: 40344607
Human2024

Modelling nausea

A Markov model of nausea across trials found disease and sex affected risk and predicted that doubling the dose every two weeks would reach 600 µg in 8 weeks with about 25% nausea.

PMID: 39044369
Review2025

Meta-analysis of nine trials

Across 9 mostly phase 2 trials with 1,525 people with type 2 diabetes, cotadutide lowered HbA1c by about 0.7 points against placebo at every dose and body weight by 1.7% at 100 µg up to 5.5% at 600 µg.

PMID: 41480597
Animal2025

A long-acting depot

A self-assembling depot formulation extended cotadutide's half-life in rats from about 10 to 100 hours, which modelling suggested could allow dosing every 14 days.

PMID: 39875074
Animal2023

Brown fat in obese mice

In obese mice, cotadutide increased thermogenic and mitochondrial markers in brown adipose tissue and reduced stress and matrix markers.

PMID: 37832793
Animal2024

Hypothalamic signals in mice

In obese mice, cotadutide shifted hypothalamic appetite-related gene expression and raised GLP-1 and glucagon receptor expression.

PMID: 38147963
Dosing

Dosing Data

Cotadutide was never approved. Trials gave 100 to 600 µg by daily subcutaneous injection, titrated up to limit nausea.

Discontinued investigational drug. Gastrointestinal side effects were common, especially at 600 µg.
ProtocolDoseFrequencyDurationRoute
Trial: phase 2b in type 2 diabetes Human studyPMID 34016612100, 200 or 300 µgOnce daily54 weeksSubcutaneous
Trial: PROXYMO in MASH with fibrosis Human studyPMID 38729399300 or 600 µgOnce daily19 weeksSubcutaneous

Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.

Microgram doses
Cotadutide was dosed in micrograms with step-up titration; it was never marketed.
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Safety

Side Effects & Contraindications

Reported Side Effects

From the trials above; there is no approved label.

● Nausea and vomiting — 35% and 17% in the 54-week trial
● Gastrointestinal effects — 92% of the 600 µg MASH group against 38% on placebo
● Stopping for side effects — 16.7% at 600 µg
● A rise in heart rate with dose

Contraindications & Cautions

An abandoned investigational drug: anything sold under the name is not the trial material.

● Anyone outside a clinical trial — the programme is closed
● Self-treatment of diabetes, kidney or liver disease
● Tested athletes — see the Sport (WADA) row below
Questions

Frequently Asked Questions

?What is cotadutide?

A peptide, once called MEDI0382, that activates the GLP-1 and glucagon receptors together. AstraZeneca's trials injected it once a day.

?Why was it stopped?

AstraZeneca's 2023 results announcement gives portfolio prioritisation. The trials record no safety finding.

?How much weight did people lose?

Less than on today's obesity drugs: 3.4% over 49 days. Its trials aimed at glucose, urinary albumin and liver fat.

?Can I get it?

Not lawfully: no regulator has approved it and no trial is recruiting.

?How long does cotadutide last in the body?

A population model estimated a half-life of about 13 hours, which is why it was given daily. Kidney impairment did not change exposure in a phase 1 study.

?Did it reduce liver fat?

Yes, in trials. It lowered liver fat and glycogen more than liraglutide in type 2 diabetes, and 600 µg improved liver fat and enzymes over 19 weeks in biopsy-proven MASH.

Bibliography

References

  1. [pubmed] Ambery PD, et al. "MEDI0382, a GLP-1/glucagon receptor dual agonist, meets safety and tolerability endpoints in a single-dose, healthy-subject, randomized, Phase 1 study." Br J Clin Pharmacol, 2018;84(10):2325-2335. PMID: 29926478.
  2. [pubmed] Ambery P, et al. "MEDI0382, a GLP-1 and glucagon receptor dual agonist, in obese or overweight patients with type 2 diabetes: a randomised, controlled, double-blind, ascending dose and phase 2a study." Lancet, 2018;391(10140):2607-2618. PMID: 29945727.
  3. [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(6):1433-1442. PMID: 34016612.
  4. [pubmed] Selvarajah V, et al. "A randomized phase 2b trial examined the effects of the glucagon-like peptide-1 and glucagon receptor agonist cotadutide on kidney outcomes in patients with diabetic kidney disease." Kidney Int, 2024;106(6):1170-1180. PMID: 39218393.
  5. [pubmed] Shankar SS, et al. "Safety and Efficacy of Novel Incretin Co-agonist Cotadutide in Biopsy-proven Noncirrhotic MASH With Fibrosis." Clin Gastroenterol Hepatol, 2024;22(9):1847-1857.e11. PMID: 38729399.
  6. [other] AstraZeneca PLC. Q1 2023 results announcement: the Phase II/III NASH trial discontinued for portfolio prioritisation (SEC Form 6-K, read September 30, 2026).
  7. [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(5):413-431. PMID: 32478287.
  8. [pubmed] Kamrul-Hasan ABM, et al. "Glycemic control, weight-loss effects, and safety of cotadutide in individuals with type 2 diabetes: A systematic review and meta-analysis." World J Diabetes, 2025;16(12):112830. PMID: 41480597.
  9. [pubmed] Parker VER, et al. "Cotadutide promotes glycogenolysis in people with overweight or obesity diagnosed with type 2 diabetes." Nat Metab, 2023;5(12):2086-2093. PMID: 38066113.
  10. [pubmed] Asano M, et al. "Safety/tolerability, efficacy and pharmacokinetics of 600-μg cotadutide in Japanese type 2 diabetes patients with a body mass index of 25 kg/m(2) or higher: A phase I, randomized, double-blind, placebo-controlled study." Diabetes Obes Metab, 2023;25(8):2290-2299. PMID: 37337366.
  11. [pubmed] Klein G, et al. "Pharmacokinetics and Safety of Cotadutide, a GLP-1 and Glucagon Receptor Dual Agonist, in Individuals with Renal Impairment: A Single-Dose, Phase I, Bridging Study." Clin Pharmacokinet, 2023;62(6):881-890. PMID: 37140727.
  12. [pubmed] Yu H, et al. "Population Pharmacokinetic Modeling of Cotadutide: A Dual Agonist Peptide of Glucagon-Like Peptide and Glucagon Receptors Administered to Participants with Type II Diabetes Mellitus, Chronic Kidney Disease, Obesity and Non-Alcoholic Steatohepatitis." Clin Pharmacokinet, 2024;63(2):255-267. PMID: 38236561.
  13. [pubmed] Yu H, et al. "Pharmacokinetic-pharmacodynamic (PK/PD) modelling of cotadutide effect in patients with chronic kidney disease and type 2 diabetes mellitus." Br J Clin Pharmacol, 2025;91(9):2672-2683. PMID: 40344607.
  14. [pubmed] Yu H, et al. "Exposure-response modeling for nausea incidence for cotadutide using a Markov modeling approach." CPT Pharmacometrics Syst Pharmacol, 2024;13(9):1582-1594. PMID: 39044369.
  15. [pubmed] Yang B, et al. "Cotadutide reversible self-assembly based long-acting injectable depot for sustained delivery of GLP-1 glucagon receptor agonists with controlled burst release." J Control Release, 2025;380:647-663. PMID: 39875074.
  16. [pubmed] Spezani R, et al. "Cotadutide improves brown adipose tissue thermogenesis in obese mice." Biochem Pharmacol, 2023;217:115852. PMID: 37832793.
  17. [pubmed] Spezani R, et al. "Cotadutide (GLP-1/Glucagon dual receptor agonist) modulates hypothalamic orexigenic and anorexigenic neuropeptides in obese mice." Peptides, 2024;173:171138. PMID: 38147963.

Sources & Citations

Studies were read from their PubMed abstracts; cotadutide has no label. Read October 7, 2026.

Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.

Last reviewed: 2026-09-30