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Metabolic & GLP-1 · Reference monograph

Gut peptide with dual GLP-1 and glucagon receptor activity

Reference compound — not available from Purity Peptides. Shown for research context.

Overview

Oxyntomodulin (OXM) is a 37-amino-acid peptide produced from proglucagon in intestinal L-cells, where it is released after meals together with GLP-1 and peptide YY. Its sequence contains the entire 29-residue glucagon molecule plus a C-terminal octapeptide extension known as intervening peptide-1. It was characterised in the early 1980s by Dominique Bataille and colleagues, who named it for its inhibitory effects on the acid-secreting oxyntic glands of the stomach.

Interest grew substantially in the 2000s, when studies at Imperial College London reported that oxyntomodulin reduced food intake and increased energy expenditure in human volunteers. Because it activates both the GLP-1 and glucagon receptors, oxyntomodulin became the conceptual template for GLP-1/glucagon co-agonist drugs now in clinical development. Native oxyntomodulin is not an approved medicine: it is rapidly degraded by DPP-4 and cleared from circulation within minutes. It remains a valuable research peptide for studying gut hormone physiology, dual-receptor pharmacology and satiety.

Mechanism studied

  1. Oxyntomodulin
  2. GLP-1R + GCGR
  3. Satiety & energy expenditure
  4. Food-intake endpoints

No receptor specific to oxyntomodulin has been identified. Instead, it acts as a dual agonist at the GLP-1 receptor and the glucagon receptor, with lower potency than the native ligands at each. GLP-1 receptor activation contributes to satiety, slowed gastric emptying and glucose-dependent insulin secretion. Glucagon receptor activation in the liver promotes glycogenolysis and gluconeogenesis and, in experimental systems, increases energy expenditure and hepatic lipid oxidation. The combination appears to offset the hyperglycaemic tendency of glucagon signalling with the insulinotropic effect of GLP-1. In GLP-1 receptor knockout mice, oxyntomodulin's anorectic effect is largely lost, implicating that receptor in food-intake responses.

Research highlights

  • 01Identified in the early 1980s from porcine intestine and named after its effect on oxyntic glands.
  • 02Released with GLP-1 and PYY from L-cells; studies after bariatric surgery have reported raised circulating levels.
  • 03Imperial College studies in the 2000s reported effects on food intake and energy expenditure in volunteers.
  • 04Studies in receptor knockout mice showed that GLP-1 receptor signalling is required for oxyntomodulin's anorectic effect.
  • 05Open questions include whether an independent receptor exists and how the optimal GLP-1 to glucagon activity ratio should be set.

Latest published research

496 papers on PubMed →

  1. Obestatin and its fragment analog Nt8U influence levels of satiety peptides in diet-induced obese mice

    Murthy STS et al. · Biochimie · 2026 Nov · PMID 42562076

  2. Nephroprotective Effects of the Dual GCGR/GLP-1R Agonist Survodutide in Hypertension-Accelerated Diabetic Kidney Disease

    Hamilton A et al. · Diabetes, obesity & metabolism · 2026 Oct 1 · PMID 42823075

  3. Kinetics and Thermodynamics of Fibril Elongation and Dissociation of Dual Glucagon-like Peptide and Glucagon Receptor Agonists

    Mohammad Karim A et al. · Langmuir : the ACS journal of surfaces and colloids · 2026 Aug 18 · PMID 42611288

  4. Interlaboratory Comparison of a Glucagon and Oxyntomodulin Immuno-LC-MS/MS Assay: Implications for Diabetes Research

    Moradian A et al. · Clinical chemistry · 2026 Jul 4 · PMID 42400596

  5. The association between glucose dynamics and energy intake in young, healthy women

    Jin Z et al. · European journal of clinical nutrition · 2026 Jul · PMID 41935112

  6. Effects of acute moderate-intensity continuous running on circulating oxyntomodulin concentrations in healthy men and women

    Jin Z et al. · Appetite · 2026 Jul 1 · PMID 41833829

  7. Distinctive patterns of glucagon and incretin responses to oral and isoglycaemic intravenous glucose load in fibrocalculous pancreatic diabetes

    Verma S et al. · Scientific reports · 2026 Jun 19 · PMID 42321243

  8. Regulators of Appetite in Mammals - Old and New players

    Fernandes JH et al. · Endocrine reviews · 2026 Jun 11 · PMID 42274231

Live feed from PubMed (NCBI) for “Oxyntomodulin”, updated 2026-10-30. Listing a paper is not an endorsement of its findings.

Registered studies

10 on ClinicalTrials.gov →

From the public ClinicalTrials.gov registry for “Oxyntomodulin”, updated 2026-10-30. Shown for research context only; Purity Peptides products are not for human use.

Key references

  1. [1]Wynne et al., 2005 — Diabetes 54:2390–2395
  2. [2]PubMed — reviews on oxyntomodulin

FAQ

  • Both are produced from the proglucagon precursor. Oxyntomodulin contains the full glucagon sequence followed by an eight-residue extension. Tissue-specific processing determines the product: pancreatic alpha cells mainly make glucagon, whereas intestinal L-cells produce oxyntomodulin, GLP-1 and GLP-2.

  • Native oxyntomodulin is cleaved by DPP-4 and cleared rapidly, giving it a very short half-life. Researchers instead used it as a template, engineering stabilised co-agonist peptides that retain dual GLP-1 and glucagon receptor activity with extended duration.

  • Oxyntomodulin is used to study gut hormone physiology after meals, the integration of GLP-1 and glucagon receptor signalling, energy expenditure, and the design principles behind dual-agonist peptides. It is also measured in studies of altered gut anatomy following bariatric surgery.

FOR RESEARCH USE ONLY.Not for human or veterinary use. Not intended to diagnose, treat, cure, or prevent any disease.

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