Head to head
Oxyntomodulin against Cotadutide
The natural gut hormone that hits both GLP-1 and glucagon receptors, and the engineered analogue built from it. Every dual agonist in development traces back to this template.
Column A
OxyntomodulinOxyntomodulin (glucagon-37)
Glucagon with eight extra amino acids on the end, which turns it into a weak dual agonist at both glucagon and GLP-1 receptors. The natural template for every GLP-1 and glucagon dual agonist.
Column B
CotadutideCotadutide (MEDI0382), GLP-1 and glucagon receptor dual agonist
A once-daily GLP-1 and glucagon dual agonist that AstraZeneca stopped developing in 2023 for what its own registry entries call strategic pipeline considerations, not safety. It leaves a randomised human record of more than a thousand people across phase 2 trials in type 2 diabetes, kidney disease and biopsy-proven MASH, and it never reached phase 3.
Side by side, on the facts we can check
| Attribute | Oxyntomodulin | Cotadutide |
|---|---|---|
| Category | Metabolic | Metabolic |
| FDA status | Not approved and not marketed anywhere. Its therapeutic relevance is as a design template. | Never approved anywhere. Development discontinued by AstraZeneca in early 2023 for stated strategic pipeline reasons (ClinicalTrials.gov NCT05668936 and NCT05517226). No phase 3 was registered. |
| Half-life | Short. Rapidly degraded by dipeptidyl peptidase-4. No single verified numeric half-life is asserted here because our sources do not agree on one. | Not reported |
| Molecular weight | 37 amino acids, residues 53 to 89 of pro-glucagon (UniProt P01275). No FDA label exists, so no label-derived mass. | Not reported |
| Mechanism | A weak dual agonist at the glucagon receptor and the GLP-1 receptor, with no dedicated receptor. The proposed appeal of that combination is that GLP-1 receptor agonism suppresses appetite while glucagon receptor agonism raises energy expenditure, so the pair might reduce intake and increase output at once. The appetite half is well demonstrated in humans. The energy expenditure half is where the evidence gets mixed. | In people, cotadutide's GLP-1 receptor action produces the familiar effects of the class: enhanced insulin secretion after meals, slower gastric emptying and reduced food intake. A 65 person phase 2a trial found postprandial glucose area under the curve fell 21.5 percent against a 6.3 percent rise on placebo, postprandial insulin rose, and gastric emptying half-time lengthened by about two hours. A 19 person energy balance study found weight loss was accounted for by a 41.3 percent reduction in energy intake with no meaningful change in energy expenditure by doubly labelled water. The glucagon receptor component is what distinguished it. In a randomised phase 2a with magnetic resonance spectroscopy, cotadutide reduced postprandial and fasting liver glycogen and liver fat more than both placebo and liraglutide, which the investigators interpreted as direct glucagon receptor action on the human liver promoting glycogenolysis. Glucagon receptor agonism also raises energy expenditure and hepatic fat oxidation in animals, and the mouse study most cited for cotadutide's liver effects (Nature Metabolism, 2020) found that its weight and glucose effects were mediated mainly through GLP-1 signalling while its effects on liver lipid, glycogen flux and mitochondrial turnover ran through the glucagon receptor, with greater fibrosis reduction than liraglutide or obeticholic acid at matched weight loss. That paper is animal work in mouse models of steatohepatitis and has been miscited as a human trial; it is not one. |
| Human studies cited | 4 | 8 |
| Legal status, US | Not a drug; endogenous hormone and research infusion peptide | Investigational, not approved |
Frequently asked questions
What is the difference between Oxyntomodulin and Cotadutide?
Oxyntomodulin: Glucagon with eight extra amino acids on the end, which turns it into a weak dual agonist at both glucagon and GLP-1 receptors. The natural template for every GLP-1 and glucagon dual agonist. Cotadutide: A once-daily GLP-1 and glucagon dual agonist that AstraZeneca stopped developing in 2023 for what its own registry entries call strategic pipeline considerations, not safety. It leaves a randomised human record of more than a thousand people across phase 2 trials in type 2 diabetes, kidney disease and biopsy-proven MASH, and it never reached phase 3.
Which has stronger research evidence, Oxyntomodulin or Cotadutide?
This database does not grade compounds. It counts what was run in people: 4 of the 4 studies cited on the Oxyntomodulin profile were human work, against 8 of 10 for Cotadutide. Those counts are of our own citation lists and understate any larger literature, and neither is a recommendation.
Are Oxyntomodulin and Cotadutide FDA-approved?
Oxyntomodulin: Not approved and not marketed anywhere. Its therapeutic relevance is as a design template.. Cotadutide: Never approved anywhere. Development discontinued by AstraZeneca in early 2023 for stated strategic pipeline reasons (ClinicalTrials.gov NCT05668936 and NCT05517226). No phase 3 was registered..
Reviewed Sep 2026. This page sets two published records side by side. It is educational, it is not medical advice, and it contains no dosing protocols or recommendations for personal use.