Oxyntomodulin

Endogenous Hormone

Oxyntomodulin is a 37-amino-acid peptide hormone produced by enteroendocrine L-cells of the gut and released after meals. It is derived from proglucagon, the same precursor protein that gives rise to glucagon and glucagon-like peptide-1 (GLP-1), and it shares sequence with both. This shared origin gives oxyntomodulin a distinctive dual pharmacology: it activates both the GLP-1 receptor and the glucagon receptor. Because it is a hormone the body makes itself, oxyntomodulin is not sold or used as a drug — this page is an educational reference to the biology that inspired an entire generation of metabolic medicines. What makes oxyntomodulin biologically compelling is that its two receptor activities are complementary rather than opposing for the purpose of weight regulation. Through the GLP-1 receptor, it reduces appetite and food intake and improves glucose handling, much like the incretin-based drugs. Through the glucagon receptor, it increases energy expenditure — that is, it raises the rate at which the body burns energy. The result is a single molecule that can, in principle, decrease calories in while increasing calories out, a combination that ordinary single-target appetite suppressants cannot achieve. This dual action is precisely why oxyntomodulin is regarded as the biological template for modern combination therapies. The success of unimolecular co-agonists validated the idea that hitting more than one metabolic receptor with one peptide can outperform single-target approaches: tirzepatide combines GIP and GLP-1 receptor activity, and retatrutide adds glucagon-receptor activity to the GLP-1/GIP combination — directly echoing oxyntomodulin's built-in GLP-1-plus-glucagon design. Native oxyntomodulin itself has a very short half-life, so drug developers have created stabilized analogs; those analogs are investigational and not a substitute for approved therapies. As a proglucagon product, oxyntomodulin sits within the incretin and gut-hormone network covered across this site. It is closely related to glucagon and to GLP-1-based medicines such as semaglutide, and it is conceptually the ancestor of dual and triple agonists like tirzepatide and retatrutide. It also acts alongside other post-meal satiety signals such as peptide YY. For background, see our overviews of the incretin effect, satiety hormones, and the use-case discussion of oxyntomodulin and weight loss. Approved obesity and diabetes care remains clinician-managed, and oxyntomodulin biology is presented here for education rather than as a treatment.