Evidence reference only. Not medical advice, not a dosing guide, and not a recommendation to use any drug.
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Cotadutide

DISCONTINUED

GLP-1 and glucagon receptor dual agonist

14
graded results
0
ongoing records
9
effect domains
Evidence spread
High evidence 0Moderate evidence 10Low evidence 3Very low evidence 1

Cotadutide has a discontinued status in the scoped regulatory record below. Results describe observations and do not provide treatment advice.

Dated status sources

DISCONTINUED Global programme; Metabolic disease development programme; Subcutaneous injection; as of 2026-07-13. European Medicines Agency

The grade rates how strong the evidence is, not how good or safe the drug is. A low or very-low grade means the evidence is thin, not that an effect is harmful or ruled out.

Thin or bounded evidence here means uncertainty remains visible. It is not evidence that an effect has been ruled out.
Cotadutide DISCONTINUED
Heart rate Increase
Low evidence

In a single-dose phase 1 study (36 on drug, 12 placebo), the balanced GLP-1/glucagon dual agonist cotadutide (MEDI0382) showed a dose-dependent increase in heart rate;...

Ambery PD et al., Br J Clin Pharmacol 2018;84(10):2325-2335 Source
Full findingIn a single-dose phase 1 study (36 on drug, 12 placebo), the balanced GLP-1/glucagon dual agonist cotadutide (MEDI0382) showed a dose-dependent increase in heart rate; treatment-emergent adverse events were mild/moderate (commonest vomiting, nausea, dizziness).
Populationsingle-dose phase 1 study, 36 on drug / 12 placebo
Fundingindustry - AstraZeneca/MedImmune (trial sponsor; inferred from registration trial)
Comparatorsplacebo
Cotadutide DISCONTINUED
Heart rate Increase
Low evidence

Increased pulse rate with cotadutide vs placebo, consistent with GLP-1 monoagonists

Asano M et al. Diabetes Obes Metab 2021;23:1859-1867 Source
PopulationOverweight Japanese T2D, phase 1/2a (n=61), up to 48 days, RCT
Fundingindustry - AstraZeneca (trial sponsor; inferred from registration trial)
Comparatorsplacebo
Thin or bounded evidence here means uncertainty remains visible. It is not evidence that an effect has been ruled out.
Cotadutide DISCONTINUED
renal Decrease
Moderate evidence

A PK/PD model from the same phase 2b CKD/T2D study predicted ~-45.6% UACR and ~-47.2% urinary-albumin change versus placebo at 26 weeks with 600 ug cotadutide,...

Yu et al., Br J Clin Pharmacol 2025;91(9):2672-2683 Source
Full findingA PK/PD model from the same phase 2b CKD/T2D study predicted ~-45.6% UACR and ~-47.2% urinary-albumin change versus placebo at 26 weeks with 600 ug cotadutide, corroborating the dose-dependent antialbuminuric effect.
PopulationSecondary PK/PD modelling analysis of the phase 2 randomised controlled trial NCT04515849 (247 participants); cotadutide 100/300/600 ug vs semaglutide 1 mg vs placebo.
Fundingindustry - AstraZeneca (cotadutide PK/PD analysis; disclosed)
Comparatorsplacebo; semaglutide 1 mg
Cotadutide DISCONTINUED
renal Decrease
Moderate evidence

In a phase 2b trial in T2D + CKD, cotadutide (GLP-1/glucagon dual agonist) dose-dependently reduced urinary albumin-to-creatinine ratio versus placebo, reaching...

Selvarajah V et al., Kidney Int 2024;106(6):1170-1180 Source
Full findingIn a phase 2b trial in T2D + CKD, cotadutide (GLP-1/glucagon dual agonist) dose-dependently reduced urinary albumin-to-creatinine ratio versus placebo, reaching significance at 300 ug (-43.9%) and 600 ug (-49.9%) at week 14, sustained to week 26, on top of standard of care.
PopulationPhase 2 double-blind randomised controlled trial (NCT04515849): 248 randomised; T2D + CKD (eGFR 20 to <90, UACR >50 mg/g); cotadutide 100/300/600 ug daily vs placebo, vs open-label semaglutide 1 mg.
Fundingindustry - AstraZeneca (cotadutide phase 2b sponsor; disclosed)
Comparatorsplacebo; semaglutide 1 mg
Thin or bounded evidence here means uncertainty remains visible. It is not evidence that an effect has been ruled out.
Cotadutide DISCONTINUED
pharmacology Decrease
Moderate evidence

Cotadutide (MEDI0382) is a balanced GLP-1/glucagon receptor dual agonist (oxyntomodulin-like) reported to activate GLP-1 and glucagon receptors at approximately 5:1,...

Nahra et al., Diabetes Care 2021;44(6):1433-1442 (phase 2b); Ambery et al., Lancet 2018 (... Source
Full findingCotadutide (MEDI0382) is a balanced GLP-1/glucagon receptor dual agonist (oxyntomodulin-like) reported to activate GLP-1 and glucagon receptors at approximately 5:1, GLP-1 activity counterbalancing glucagon-driven hepatic glucose output while glucagon adds energy expenditure and hepatic-fat-lowering. In a 54-week phase 2b study in overweight/obesity + T2D it reduced body weight, HbA1c and liver fat vs placebo and vs liraglutide; AstraZeneca reportedly deprioritised it.
PopulationAdults with overweight/obesity and T2D; phase 2a (n~65) and phase 2b 54-week study (n~834), double-blind, placebo- and liraglutide-controlled
Fundingindustry-AstraZeneca
Comparatorsplacebo; liraglutide
Cotadutide DISCONTINUED
pharmacology Not directional
Low evidence

GLP-1R/GcgR dual agonist with GcgR-biased lipid engagement; lipid C18 moiety gives stronger GcgR engagement vs SAR425899; once-daily s.c.

Li Y et al. PNAS 2023;120:e2303696120 Source
PopulationIn-vitro/structural (cryo-EM) and PK
Fundingindustry - AstraZeneca (trial sponsor; inferred from registration trial)
ComparatorsSAR425899; peptide 15
Thin or bounded evidence here means uncertainty remains visible. It is not evidence that an effect has been ruled out.
Cotadutide DISCONTINUED
Liver and MASH Decrease
Moderate evidence

Cotadutide 300 µg improved AST, ALT, PRO-C3, FIB-4, NAFLD fibrosis score vs placebo (not seen with liraglutide); promotes hepatic glycogenolysis and liver fat...

Nahra R et al. Diabetes Care 2021;44:1433-1442 Source
Full findingCotadutide 300 µg improved AST, ALT, PRO-C3, FIB-4, NAFLD fibrosis score vs placebo (not seen with liraglutide); promotes hepatic glycogenolysis and liver fat reduction via GcgR
PopulationOverweight/obese T2D, phase 2b ad hoc (n=834, 54 wk) and phase 2a glycogen study (NCT03555994)
Fundingindustry-AstraZeneca
Comparatorsplacebo; liraglutide 1.8 mg
Cotadutide DISCONTINUED
Liver and MASH Decrease
Very low evidence

Cotadutide resolved NASH/fibrosis in preclinical models more than liraglutide or OCA at matched weight loss; GcgR drives hepatic lipid/mitochondrial effects

Boland ML et al. Nat Metab 2020;2:413-431 Source
PopulationMouse NASH models + GLP-1R KO mice (preclinical mechanism)
Fundingacademic/independent analysis (manufacturer not study sponsor; per-study COI not individually audited)
Comparatorsliraglutide; obeticholic acid
Thin or bounded evidence here means uncertainty remains visible. It is not evidence that an effect has been ruled out.
Cotadutide DISCONTINUED
weight-loss Decrease
Moderate evidence

Once-daily cotadutide reduced body weight vs placebo in overweight/obese T2D

Ambery P et al. Lancet 2018;391:2607-2618 Source
PopulationOverweight/obese T2D adults, phase 2a (n=51 randomised, 22 cotadutide analysed), 41 days, RCT, double-blind, placebo-controlled, up to 200 µg s.c.
Fundingindustry-AstraZeneca
Comparatorsplacebo
Cotadutide DISCONTINUED
weight-loss Decrease
Moderate evidence

54-week cotadutide reduced weight vs placebo; 200 µg similar to liraglutide 1.8 mg, 300 µg greater than liraglutide

Nahra R et al. Diabetes Care 2021;44:1433-1442 Source
PopulationOverweight/obesity + T2D on metformin (n=834), phase 2b, 54 wk, RCT double-blind, comparator open-label liraglutide 1.8 mg
Fundingindustry-AstraZeneca
Comparatorsplacebo; liraglutide 1.8 mg
Thin or bounded evidence here means uncertainty remains visible. It is not evidence that an effect has been ruled out.
Cotadutide DISCONTINUED
glycaemic Decrease
Moderate evidence

Cotadutide reduced post-MMTT glucose AUC vs placebo in overweight/obese T2D (phase 2a, 41 days).

Ambery P et al. Lancet 2018;391:2607-2618 Source
PopulationOverweight/obese T2D, phase 2a (n=51) and phase 2b (n=834), up to 54 wk, RCT
Fundingindustry-AstraZeneca
Comparatorsplacebo; liraglutide 1.8 mg
Thin or bounded evidence here means uncertainty remains visible. It is not evidence that an effect has been ruled out.
Cotadutide DISCONTINUED
insulin-beta-cell Mixed
Moderate evidence

The GLP-1/glucagon dual cotadutide reduced fasting hepatic glycogen ~38% vs placebo and ~41% vs liraglutide (13C-MRS), confirming GCGR engagement promoting...

Parker VER et al., Nat Metab 2023;5(12):2086-2093 Source
Full findingThe GLP-1/glucagon dual cotadutide reduced fasting hepatic glycogen ~38% vs placebo and ~41% vs liraglutide (13C-MRS), confirming GCGR engagement promoting glycogenolysis (glycogen not fully depleted); mouse receptor dissection shows cotadutide's glucose control and weight loss are predominantly GLP-1-mediated while liver lipid/glycogen-flux effects are glucagon-mediated.
PopulationOverweight/obese T2D (human glycogen MRS) + mouse dissection
Fundingindustry-AstraZeneca
Comparatorsplacebo; liraglutide
Thin or bounded evidence here means uncertainty remains visible. It is not evidence that an effect has been ruled out.
Cotadutide DISCONTINUED
lipids-lipoprotein Decrease
Moderate evidence

Improvements in lipid profile with cotadutide 300 µg vs placebo

Nahra R et al. Diabetes Care 2021;44:1433-1442 Source
PopulationOverweight/obese T2D, phase 2b (n=834), 54 wk, RCT
Fundingindustry-AstraZeneca
Comparatorsplacebo; liraglutide 1.8 mg
Thin or bounded evidence here means uncertainty remains visible. It is not evidence that an effect has been ruled out.
Cotadutide DISCONTINUED
Stomach and gut Increase
Moderate evidence

GI adverse events (nausea, vomiting) most common; decreased over time

Nahra R et al. Diabetes Care 2021;44:1433-1442 Source
PopulationOverweight/obese T2D, phase 2a & 2b
Fundingindustry-AstraZeneca
Comparatorsplacebo; liraglutide 1.8 mg