Oxyntomodulin
Oxyntomodulin (glucagon-37)
Written by Aaron CuhaReviewed Sep 2026
Also known as: OXM, Glucagon-37, Bioactive enteroglucagon
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.
Overview
Oxyntomodulin is the glucagon sequence plus an eight-residue tail, KRNRNNIA. That single structural fact explains its entire pharmacology and is why it belongs on this site. It has no receptor of its own. It is a weak agonist at the glucagon receptor and a weak agonist at the GLP-1 receptor, and hitting both at once is exactly the design every modern dual agonist copies, including survodutide, mazdutide and pemvidutide.
It is released after meals from intestinal L cells, from the same pro-glucagon precursor that makes GLP-1 and GLP-2, in proportion to how much you ate. The human trials of the native peptide are small, old and genuinely positive, and they stop well short of anything therapeutic.
Mechanism of action
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.
Human evidence
Small, old, and real. Native oxyntomodulin has been infused into and injected by volunteers in randomised placebo-controlled studies, and it reduced food intake and bodyweight. The trials are tiny by modern standards and none went beyond four weeks.
- Acute intravenous infusion in 13 healthy volunteers cut buffet intake by 19.3% and suppressed ghrelin, without nausea.
- Four weeks of self-administered subcutaneous oxyntomodulin produced 2.3 kg of weight loss against 0.5 kg on control.
- It is additive with PYY3-36 on food intake in overweight and obese people.
- Triple infusions of GLP-1 plus oxyntomodulin plus PYY have been studied against gastric bypass and caloric restriction, including a metabolomic comparison.
What this does not tell you: The largest randomised trial of the native peptide ran four weeks in a small group of volunteers. There is no phase 3 programme, no outcome data, no long-term safety data and no approved product. The energy expenditure claim, which is the most-repeated thing about oxyntomodulin, rests substantially on rodent work and the human data on that specific endpoint are mixed. Everything clinically meaningful in this space has happened in engineered analogues, not the hormone.
Reading the research record
Oxyntomodulin's value to a reader is historical and structural rather than therapeutic. If you want to understand why a whole generation of drugs pairs GLP-1 receptor agonism with glucagon receptor agonism, the answer is that the body already does it, weakly, with a peptide that is glucagon plus eight residues. Every dual agonist on this site is an attempt to do that harder and for longer.
The honest caution is on energy expenditure. That is the exciting half of the dual-agonist pitch, it is the half that comes mostly from rodents, and the one human trial designed to separate it out found a mixed picture. A page that repeats the metabolism-boosting claim without naming the species has not read the trial.
The evidence, charted
Fig. 1 · evidence composition
4of 4 citations (100%) are in people
Every citation cited here is Human work; no other study type is cited on this page. This count is of our own citation list and understates any literature larger than the sources we cite.
Fig. 2 · evidence over time
Evidence spans 4 distinct years, 2003 to 2023, counted from the citation list on this page.
Fig. 3 · legal status at a glance
US
Not approved
UK
Approved
AU
Not approved
CA
Not approved
Approved in 1 of 4, prescription route in 0, not approved in 3. A jurisdiction's classification is a regulatory fact, not a verdict on the science; see Legal status below for the full text and any notes.
Fig. 4 · dose response
No human dose response curve exists
We draw this figure where the data supports it. For this compound in humans it does not, so the panel stays empty rather than borrowing an animal curve and implying it transfers.
Key studies & citations
- Human2003
Oxyntomodulin suppresses appetite and reduces food intake in humans
13 healthy volunteers, randomised double-blind placebo-controlled crossover. Buffet energy intake fell 19.3% and 12-hour intake 11.3%, with ghrelin suppressed. Notably it caused no nausea and did not change how food tasted, which separates it from some later drugs in the class.
Journal of Clinical Endocrinology and Metabolism - Human2005
Subcutaneous oxyntomodulin reduces body weight in overweight and obese subjects: a double-blind, randomized, controlled trial
Self-administered three times daily before meals for four weeks. Bodyweight fell 2.3 kg against 0.5 kg on control (p = 0.0106), roughly 0.45 kg a week, with energy intake at the study meal down 25% at the start and 35% by the end.
Diabetes - Human2015
Effect of oxyntomodulin, glucagon, GLP-1, and combined glucagon plus GLP-1 infusion on food intake, appetite, and resting energy expenditure
The trial that separates the appetite claim from the energy expenditure claim by running oxyntomodulin against its two component signals and against the combination. Read this before believing the raises-your-metabolism half of the story.
Journal of Clinical Endocrinology and Metabolism - Human2023
Tripeptide gut hormone infusion does not alter food preferences or sweet taste function in volunteers with obesity and prediabetes or diabetes but promotes restraint eating
A negative secondary analysis, included because it is negative. Combining GLP-1, oxyntomodulin and PYY did not change what people wanted to eat or how sweet things tasted.
Diabetes, Obesity and Metabolism
Frequently asked questions
What is oxyntomodulin, in one sentence?
Glucagon with an eight amino acid tail, which makes it a weak agonist at both the glucagon and the GLP-1 receptor at the same time.
Does it cause weight loss?
In the one four-week randomised trial of the native peptide, 2.3 kg against 0.5 kg on control. That is real and it is a small, short trial with no follow-up programme.
Why does it matter if it is not a drug?
Because it is the template. Survodutide, mazdutide, pemvidutide and the rest of the GLP-1 and glucagon dual agonists are engineered versions of what oxyntomodulin does naturally.
Does it boost metabolism?
That claim is the shakiest part of the story. It comes largely from rodent work, and the human trial built specifically to separate appetite effects from energy expenditure effects found a mixed result.