Peptide LibraryCotadutide
Also known as: MEDI0382, GLP-1/glucagon dual agonist
Cotadutide (also called MEDI0382 or GLP-1/glucagon dual agonist) is a glucagon agonist in the GLP-1 Agonist class. Cotadutide is a balanced dual agonist at the GLP-1 and glucagon receptors, based on the oxyntomodulin scaffold — the endogenous gut hormone that naturally activates both.
For research use only.
Key Facts
- CAS
- 1686108-82-2
- Molecular Weight (MW)
- —
- Half-life
- ~13 hours (sc) in human PK models
- FDA status
- Investigational New Drug (IND)
- Evidence level
- Clinical Trial Evidence
- Human dose established
- Yes
- Administration Route
- Subcutaneous
- Frequency
- Once daily
- Last updated
- Nov 7, 2026
- Reviewed
- Nov 7, 2026
- Targets
- GLP-1 receptorGlucagon receptor
Research summary
AstraZeneca GLP-1/glucagon receptor dual agonist studied for NASH and type 2 diabetes. Clinical development has been mixed; not FDA-approved.
Research evidence
- Regulatory review (FDA label)None in reviewed sources
- Controlled human trials4 reviewed sources
- Early or uncontrolled human studies1 reviewed source
- Lab & animal studiesNone in reviewed sources
How it works
Each step shows whether the sources Peptide Library has reviewed include that kind of research. Counts are reviewed sources, not every study ever published. Reviews and programme summaries that describe human use are shown as "reported", not as trials, and registered trials without published results are listed but not counted. A higher step means research has progressed further; it does not mean a compound works better or is safer. Compounds whose evidence has not been reviewed yet show "Not reviewed" instead of a guess.
Peptide Library's Cotadutide profile summarises 5 cited studies listed in the Science section, the compound's regulatory status, and research-protocol parameters reported for it. It is a research reference, not medical advice.
Cotadutide dosage evidence
Cotadutide has no approved dosage. Human dosing comes from AstraZeneca's phase 2 trials, which gave injections under the skin of 50–600 mcg, once daily where the abstracts state the schedule: 100, 200 or 300 mcg for 54 weeks in adults with type 2 diabetes and overweight or obesity, and up to 600 mcg in trials in kidney disease and liver disease. AstraZeneca stopped developing cotadutide for strategic pipeline reasons, so none of these doses went on to phase 3.
| Human dosing established | Yes |
|---|---|
| Studied dose range | 50–600 mcg once daily in phase 2 trials |
| Route | Subcutaneous |
| Frequency | Once daily |
| Duration studied | 32 days to 54 weeks in the published phase 2 trials |
| Titration | The diabetic kidney disease trial raised the dose step by step to 100, 300 or 600 mcg; the step schedule is not given in the indexed abstract. |
| Evidence level | Clinical Trial Evidence |
| Last reviewed | 2026-11-07 |
Research-reported dosing
Doses as studied, one row per regimen. Different trials used different regimens; they are listed separately rather than averaged.
| Study / context | Population | Dose | Route | Frequency | Duration | Outcome studied | Source |
|---|---|---|---|---|---|---|---|
| Phase 2b, type 2 diabetes with overweight or obesity (NCT03235050)Clinical trial · Randomized, double-blind, placebo-controlled phase 2b trial with open-label liraglutide | Adults with BMI ≥25 and type 2 diabetes on metformin (n=834) | 100, 200 or 300 mcg (compared with placebo and liraglutide 1.8 mg) | Subcutaneous | Not stated in the indexed abstract | 54 weeks (co-primary endpoints at week 14) | HbA1c and body weight fell more than with placebo at weeks 14 and 54; weight loss with 300 mcg was greater than with liraglutide 1.8 mg | 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. |
| Phase 2a, type 2 diabetes with chronic kidney disease (NCT03550378)Clinical trial · Randomized, placebo-controlled phase 2a trial | Adults with type 2 diabetes, BMI 25–45 and eGFR 30–59 (41 analysed) | 50–300 mcg | Subcutaneous | Once daily | 32 days | Lower glucose after a mixed meal and -3.41 kg body weight against -0.13 kg with placebo | Efficacy and safety of cotadutide, a dual glucagon-like peptide-1 and glucagon receptor agonist, in a randomized phase 2a study of patients with type 2 diabetes and chronic kidney disease. Diabetes Obes Metab. 2022. |
| Phase 2b, diabetic kidney disease (NCT04515849)Clinical trial · Randomized phase 2b trial, double-blind for cotadutide and placebo | Adults with type 2 diabetes and chronic kidney disease (n=248) | Raised to 100, 300 or 600 mcg (compared with placebo and semaglutide 1 mg weekly) | Subcutaneous | Once daily | 26 weeks | Urine albumin-to-creatinine ratio fell versus placebo at week 14, significantly at 300 mcg (-43.9%) and 600 mcg (-49.9%) | 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. |
| PROXYMO — phase 2, MASH with fibrosis (NCT04019561)Clinical trial · Randomized, double-blind, placebo-controlled trial | Adults with biopsy-proven noncirrhotic MASH with fibrosis (n=74) | 300 or 600 mcg | Subcutaneous | Not stated in the indexed abstract | 19 weeks | Liver fat, ALT and AST improved significantly with 600 mcg; treatment-related discontinuation 16.7% with 600 mcg, 7.7% with 300 mcg and 4.2% with placebo | Safety and Efficacy of Novel Incretin Co-agonist Cotadutide in Biopsy-proven Noncirrhotic MASH With Fibrosis. Clin Gastroenterol Hepatol. 2024. |
| Phase 1, hepatic impairment — stopped early (NCT05517226)Clinical trial · Phase 1 pharmacokinetic study, terminated | Participants with hepatic impairment (n=24) | A single protocol dose ("Dose A") | Subcutaneous | Per trial protocol | Per trial protocol | Terminated. The registry gives the reason as discontinuing the development of cotadutide based on strategic pipeline considerations, not a new safety signal | NCT05517226 — Pharmacokinetics of Cotadutide in Participants With Hepatic Impairment |
Where sources disagree
- Cotadutide's development was discontinued. ClinicalTrials.gov records for its last studies say the decision was based on strategic pipeline considerations and not on new safety findings. No phase 3 trial was run, so no dose was carried forward.
- The trials used daily injections in micrograms. These doses are not interchangeable with weekly GLP-1 drugs dosed in milligrams, such as semaglutide or survodutide.
- Cotadutide is described as an oxyntomodulin-related dual GLP-1 and glucagon agonist, but it is a different molecule from native oxyntomodulin; the native hormone's infusion studies are not evidence for cotadutide doses, and the reverse.
Handling & administration
- Injection Sites
- Per protocol
- Timing Notes
- Investigational (T2D, CKD/T2D, metabolic endpoints)
Sequence & molecular data
| Molecular formula | C167H252N42O55 |
|---|---|
| Molecular weight | — |
| CAS number | 1686108-82-2 |
| Half-life | ~13 hours (sc) in human PK models |
| Appearance | Investigational sc formulation |
| Formulation | Lyophilized Powder |
| PubChem CID | 134694273 |
| FDA UNII | QL6A9B13HW |
| ChEMBL | CHEMBL4297630 |
| DrugBank | DB15194 |
Identifiers link to the public PubChem, FDA Substance Registration (UNII), ChEMBL and DrugBank records for the same entity.
Science
Mechanism of Action
Cotadutide is a balanced dual agonist at the GLP-1 and glucagon receptors, based on the oxyntomodulin scaffold — the endogenous gut hormone that naturally activates both. GLP-1 receptor activation supplies glucose-dependent insulin secretion, glucagon suppression and reduced appetite, while glucagon receptor activation increases hepatic energy expenditure, glycogenolysis and fatty-acid oxidation. The intended result is greater weight and hepatic fat reduction than GLP-1 agonism alone, with the incretin arm offsetting glucagon-driven glucose elevation. Its development has centred on liver endpoints, where the glucagon component acts directly on hepatocytes.
Origin
Synthetic oxyntomodulin-related dual agonist.
Targets
Studies
- 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
- Safety and Efficacy of Novel Incretin Co-agonist Cotadutide in Biopsy-proven Noncirrhotic MASH With Fibrosis
- Characterisation of cotadutide's dual GLP-1/glucagon receptor agonistic effects on glycaemic control using an in vivo human glucose regulation quantitative systems pharmacology model
- Cotadutide promotes glycogenolysis in people with overweight or obesity diagnosed with type 2 diabetes
- Efficacy and safety of cotadutide, a dual glucagon-like peptide-1 and glucagon receptor agonist, in a randomized phase 2a study of patients with type 2 diabetes and chronic kidney disease
Research statistics
49 PubMed publications · 28.6% human clinical research · 24 registered trials
Counts of published research through 2026-11-01, not evidence that it works. Publications by year, study types and trials · How publications are counted
Regulatory & research status
Cotadutide has been studied under an Investigational New Drug application. It is not approved for marketing.
| FDA status | Investigational New Drug (IND) |
|---|---|
| Availability | Research-Only |
| WADA (sport) | Banned in Sport |
| Library classification | Clinical Trial |
How FDA approval, compounding and research-only status differ
Benefits
Cotadutide side effects
The effects below are those reported in Cotadutide clinical trials; long-term safety data may still be limited.
Side Effects
- GI adverse events
- Increased heart rate (glucagon class)
Storage & stability
This compound is not supplied as a powder to be mixed, so the freeze-dried powder and reconstitution handling described for research peptides does not apply. Storage conditions are product-specific: follow the label or packaging of the product itself.
Cotadutide: frequently asked questions
What is Cotadutide?
AstraZeneca GLP-1/glucagon receptor dual agonist studied for NASH and type 2 diabetes. Clinical development has been mixed; not FDA-approved.
How does Cotadutide work?
Cotadutide is a balanced dual agonist at the GLP-1 and glucagon receptors, based on the oxyntomodulin scaffold — the endogenous gut hormone that naturally activates both. GLP-1 receptor activation supplies glucose-dependent insulin secretion, glucagon suppression and reduced appetite, while glucagon receptor activation increases hepatic energy expenditure, glycogenolysis and fatty-acid oxidation.
Is Cotadutide FDA approved?
No. Cotadutide is investigational: it is in clinical development and has not been approved by the FDA for any indication. Investigational status means trials are ongoing or complete but regulatory review has not resulted in approval, and efficacy and safety are still being established.
What is the half-life of Cotadutide?
Reported half-life for Cotadutide is ~13 hours (sc) in human PK models. Half-life describes how long the compound persists in circulation, not how long any effect lasts, and published figures vary with route of administration, formulation and the population studied.
Is Cotadutide banned in sport?
Cotadutide is recorded here as prohibited in sport. Athletes subject to anti-doping rules should check the current WADA Prohibited List directly, since it is revised annually and classifications change.
What peptides are similar to Cotadutide?
Compounds most often compared with Cotadutide include Retatrutide, Survodutide, Pemvidutide and Mazdutide. They are grouped by shared mechanism or research area rather than by equivalence, and their regulatory status and evidence base differ.
References
- 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, 2024External reference
- Safety and Efficacy of Novel Incretin Co-agonist Cotadutide in Biopsy-proven Noncirrhotic MASH With Fibrosis — Clin Gastroenterol Hepatol, 2024External reference
- Characterisation of cotadutide's dual GLP-1/glucagon receptor agonistic effects on glycaemic control using an in vivo human glucose regulation quantitative systems pharmacology model — Br J Pharmacol, 2024External reference
- Cotadutide promotes glycogenolysis in people with overweight or obesity diagnosed with type 2 diabetes — Nat Metab, 2023External reference
- Efficacy and safety of cotadutide, a dual glucagon-like peptide-1 and glucagon receptor agonist, in a randomized phase 2a study of patients with type 2 diabetes and chronic kidney disease — Diabetes Obes Metab, 2022External reference
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Compiled by Peptide Library Editorial · Reviewed Aug 30, 2026 · Updated Nov 7, 2026 · Version 2
This Cotadutide profile is compiled from published literature (5 cited studies linked above), public regulatory records and chemical registries. It describes what research reports; it is not medical advice, and nothing here is a dosing recommendation for humans. Peptide Library does not sell peptides. Editorial policy · How profiles are compiled · Report an error
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