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Evidence: MediumPeptideResearch ChemicalEndogenous gut hormoneGLP-1 + glucagon receptor co-agonistNot a medicine

Oxyntomodulin

The gut hormone that inspired the GLP-1/glucagon dual agonists

Oxyntomodulin is a natural gut hormone made from the same gene as glucagon and released after eating. It activates both the GLP-1 receptor and the glucagon receptor, and in small human trials it reduced appetite and food intake, raised energy expenditure, and produced modest weight loss. It is the blueprint for dual agonists such as survodutide and mazdutide.

At a Glance Read Research →
Overview

What is it?

Oxyntomodulin is a product of the glucagon gene made in the lower intestine and released after meals. It acts on both the GLP-1 receptor and the glucagon receptor, a combination drug designers later copied. Its plasma half-life is about 12 minutes.

London studies in the 2000s tested it for appetite. An infusion in healthy volunteers cut food intake at a buffet by 19% and suppressed the hunger hormone ghrelin. In overweight and obese volunteers, self-injection three times a day before meals for four weeks led to 2.3 kg of weight loss against 0.5 kg on saline, and another trial found it raised activity-related energy expenditure by 26% while reducing intake. Given with PYY, it cut intake by 43%.

A 2018 study found native oxyntomodulin increased glucose-dependent insulin secretion in obese people with and without type 2 diabetes, comparable to liraglutide and independent of weight loss. A 2019 trial infused GLP-1, oxyntomodulin and PYY together for four weeks and found greater weight loss and better glucose control than saline.

Native oxyntomodulin lasts minutes and was never developed as a medicine. Its dual action is the template for longer-acting GLP-1/glucagon co-agonists such as survodutide and mazdutide, which have their own entries.

Structured data

At a Glance

Every value in this table is printed from the Grey Peptides dataset, the same record the compound explorer and comparison tool read, so the three can never disagree.

ClassA natural gut hormone from the glucagon gene, released after meals, that activates both GLP-1 and glucagon receptors; infused or injected in small trials it reduced appetite and weight, and it is the model for the GLP-1/glucagon dual agonists now in development.
FormulaC192H295N59O60S
Molecular weight4422 g/mol
Half-life12 minutes in plasma during infusion in six volunteers (PMID 3147901)
US statusResearch Chemical
Evidence levelMedium
Last reviewed2026-10-03
Interactive

Half-Life: How Much Remains

The dataset records a half-life of 12 minutes in plasma during infusion in six volunteers (PMID 3147901) for Oxyntomodulin. After each half-life, half of what was in the circulation is gone, so about 3% remains after five. Real clearance varies with the person, the dose, the route and kidney or liver function; this is arithmetic on a published figure, not a dosing tool.

Time since a single dose
ElapsedTimeRemaining
1 half-life12 min50% remaining
2 half-lives24 min25% remaining
3 half-lives36 min12.5% remaining
4 half-lives48 min6.25% remaining
5 half-lives60 min3.125% remaining
Evidence

Published Research

Studies of oxyntomodulin, from their PubMed abstracts.

Human2005

Four weeks of injections in obesity

Subcutaneous oxyntomodulin three times daily before meals for 4 weeks reduced body weight by 2.3 kg versus 0.5 kg on saline (P = 0.0106), with energy intake 25-35% lower at study meals.

PMID: 16046306
Human2003

Appetite in healthy volunteers

IV oxyntomodulin reduced buffet energy intake by 19.3% and 12-hour intake by 11.3%, lowered hunger scores and suppressed preprandial ghrelin, without nausea.

PMID: 14557443
Human2006

Energy expenditure

In overweight and obese volunteers, oxyntomodulin reduced meal intake by 17.3%, raised activity-related energy expenditure by 26.2% and total energy expenditure by 9.4%, without changing resting expenditure.

PMID: 16619056
Human2018

Insulin secretion in obesity and type 2 diabetes

Native oxyntomodulin at 3.0 pmol/kg/min increased insulin secretion and blunted glucose excursions in obese subjects with and without type 2 diabetes, comparable to liraglutide.

PMID: 29545266
Human2010

Added to PYY3-36

Co-infusion of PYY3-36 and oxyntomodulin reduced energy intake by 42.7% versus saline, significantly more than either hormone alone.

PMID: 20357366
Human2019

GLP-1, oxyntomodulin and PYY together

A 4-week infusion of the three hormones produced weight loss of 4.4 kg versus 2.5 kg with saline and a larger fall in fructosamine, and was well tolerated.

PMID: 31177183
Human1988

Pharmacokinetics

In six volunteers, synthetic oxyntomodulin had a plasma half-life of 12 minutes, reduced pentagastrin-stimulated gastric acid secretion, and slightly raised insulin and C-peptide.

PMID: 3147901
Safety

Side Effects & Contraindications

Reported Side Effects

From the short trials above.

● No nausea during the 2003 infusion study
● The 4-week triple-hormone infusion was well tolerated

Contraindications & Cautions

There is no label.

● Not approved for any use
Questions

Frequently Asked Questions

?What is oxyntomodulin?

A natural gut hormone made from the glucagon gene and released after meals. It activates both GLP-1 and glucagon receptors.

?Does oxyntomodulin cause weight loss?

In a 4-week trial of injections three times a day, volunteers lost 2.3 kg against 0.5 kg on saline. It reduces appetite and, in one study, raised activity-related energy expenditure.

?Why isn't oxyntomodulin a drug?

It lasts about 12 minutes in blood, so drug makers built longer-acting molecules with the same dual action.

?How does it relate to survodutide and mazdutide?

Those are synthetic GLP-1/glucagon dual agonists designed to copy oxyntomodulin's two-receptor action while lasting much longer.

Bibliography

References

  1. [other] PubChem CID 16144019, Oxyntomodulin: formula C192H295N59O60S, molecular weight 4422. Read October 3, 2026. https://pubchem.ncbi.nlm.nih.gov/compound/16144019
  2. [fda] FDA. Drugs@FDA (openFDA): no application on record for oxyntomodulin. Read October 3, 2026.
  3. [clinical-trial] Wynne K, et al. "Subcutaneous oxyntomodulin reduces body weight in overweight and obese subjects: a double-blind, randomized, controlled trial." Diabetes, 2005;54(8):2390-5. PMID: 16046306.
  4. [clinical-trial] Cohen MA, et al. "Oxyntomodulin suppresses appetite and reduces food intake in humans." J Clin Endocrinol Metab, 2003;88(10):4696-701. PMID: 14557443.
  5. [clinical-trial] Wynne K, et al. "Oxyntomodulin increases energy expenditure in addition to decreasing energy intake in overweight and obese humans: a randomised controlled trial." Int J Obes (Lond), 2006;30(12):1729-36. PMID: 16619056.
  6. [clinical-trial] Shankar SS, et al. "Native Oxyntomodulin Has Significant Glucoregulatory Effects Independent of Weight Loss in Obese Humans With and Without Type 2 Diabetes." Diabetes, 2018;67(6):1105-1112. PMID: 29545266.
  7. [clinical-trial] Field BC, et al. "PYY3-36 and oxyntomodulin can be additive in their effect on food intake in overweight and obese humans." Diabetes, 2010;59(7):1635-9. PMID: 20357366.
  8. [clinical-trial] Behary P, et al. "Combined GLP-1, Oxyntomodulin, and Peptide YY Improves Body Weight and Glycemia in Obesity and Prediabetes/Type 2 Diabetes: A Randomized, Single-Blinded, Placebo-Controlled Study." Diabetes Care, 2019;42(8):1446-1453. PMID: 31177183.
  9. [pubmed] Schjoldager BT, et al. "Oxyntomodulin: a potential hormone from the distal gut. Pharmacokinetics and effects on gastric acid and insulin secretion in man." Eur J Clin Invest, 1988;18(5):499-503. PMID: 3147901.

Sources & Citations

Studies were read from their PubMed records, October 3, 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. Consult a licensed healthcare provider before making health decisions.

Last reviewed: 2026-10-03