Oxyntomodulin
Oxyntomodulin is a 37-aa gut peptide and dual GLP-1R/glucagon receptor agonist released post-meal. Its combined receptor activity suppresses appetite while simultaneously increasing energy expenditure — the mechanistic rationale for multi-receptor incretin drugs.
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Compound Profile
Oxyntomodulin
Key Data
Research reference only
Research Focus
Preclinical data
⚠ Research & Educational Use Only. Oxyntomodulin is a research chemical documented here for scientific education. All information references peer-reviewed literature and preclinical/clinical study data. Not for human consumption. Not medical advice. Consult a licensed researcher or healthcare professional before any laboratory use.
- Dual GLP-1R and glucagon receptor agonism — suppresses appetite (GLP-1R) while increasing energy expenditure (glucagon-R)
- Reduces food intake by 19-25% in human IV infusion studies (Cohen et al., J Clin Invest 2003)
- Increases resting energy expenditure by approximately 17-25% via glucagon receptor-driven thermogenesis
- Oxyntomodulin is not FDA-approved for human use. It is a research chemical for scientific study only.
Research At a Glance
- Dual GLP-1R and glucagon receptor agonism — suppresses appetite (GLP-1R) while increasing energy expenditure (glucagon-R)
- Reduces food intake by 19-25% in human IV infusion studies (Cohen et al., J Clin Invest 2003)
- Increases resting energy expenditure by approximately 17-25% via glucagon receptor-driven thermogenesis
- Net caloric deficit from combination of reduced intake + increased expenditure (superior to GLP-1R agonism alone in rodents)
In Plain English
Simple summaryOxyntomodulin is a 37-amino acid peptide produced by the same gut L-cells that secrete GLP-1 -- it's actually released simultaneously with GLP-1 after eating and contains the GLP-1 sequence plus a C-terminal extension derived from glucagon. That structure means it activates both GLP-1 and glucagon receptors simultaneously, making it a natural dual agonist before the concept was engineered into drugs like tirzepatide. The dual activation matters: GLP-1 suppresses appetite and slows gastric emptying; glucagon receptor activation increases energy expenditure and promotes fat oxidation. Research subjects given oxyntomodulin infusions show greater calorie reduction than those given GLP-1 alone, suggesting the glucagon component adds meaningful metabolic benefit beyond satiety.
- Dual GLP-1R and glucagon receptor agonism — suppresses appetite (GLP-1R) while increasing energy expenditure (glucagon-R)
- Reduces food intake by 19-25% in human IV infusion studies
- Increases resting energy expenditure by approximately 17-25% via glucagon receptor-driven thermogenesis
The full scientific detail, mechanisms, citations, and dosing data, follows below.
What is Oxyntomodulin?
Tap any underlined term for an instant definition.
Oxyntomodulin (OXM) is a 37-amino acid post-translational product of proglucagon, the same precursor that gives rise to glucagon (in the pancreatic alpha cells) and GLP-1 and GLP-2 (in intestinal L-cells). OXM comprises the full glucagon sequence plus an 8-amino acid C-terminal extension (glicentin-related pancreatic peptide sequence).
OXM is co-secreted with GLP-1 by intestinal L-cells in proportion to meal size. Its defining pharmacological characteristic is dual agonism at both the GLP-1 receptor (GLP-1R) and the glucagon receptor (GCGR), with lower potency at each individual receptor compared to native GLP-1 or glucagon.
**The dual-agonism advantage:** - GLP-1R agonism: suppresses appetite, slows gastric emptying, and potentiates glucose-dependent insulin secretion - GCGR agonism: stimulates hepatic glycogenolysis, promotes lipolysis, and critically — increases energy expenditure via brown adipose tissue (BAT) thermogenesis and hepatic lipid oxidation
The net result is a compound that produces greater weight loss than GLP-1R agonism alone in preclinical studies, not just by reducing caloric intake but by simultaneously increasing metabolic rate. This is conceptually superior to single-mechanism weight loss approaches.
Key human evidence: Wynne et al. (2005) administered OXM SC before meals for 4 weeks to overweight adults, producing 2.3 kg weight loss vs 0.5 kg placebo — a significant difference in a short study. Subsequent infusion studies confirmed both reduced appetite and increased 24-hour energy expenditure.
OXM served as the structural and mechanistic template for the development of dual-agonist drugs including cotadutide (AstraZeneca GLP-1R/GCGR dual agonist), SAR425899 (Sanofi), and elements of the mazdutide program. These drugs attempt to optimize the GLP-1R:GCGR agonism ratio for maximum weight loss with acceptable GI tolerability.
By the Numbers
Key Research Benefits
Documented effects observed in preclinical and clinical studies on Oxyntomodulin. See all Metabolic & Weight peptides for comparison.
Side Effects & Risks
Adverse effects reported in the research literature. All data sourced from preclinical and clinical study reports. View all peptides' side effects →
Dosing Data from the Literature
Doses referenced below are sourced from published preclinical and clinical studies. Use the peptide dose calculator to convert these values to injection volume.
Oxyntomodulin research primarily uses IV or SC infusion protocols:
Human IV infusion: 3-4.5 pmol/kg/min subcutaneous infusion × 4 weeks (Wynne et al., JCEM 2005): −2.3 kg vs placebo SC injection studies (mice): 50-400 nmol/kg TID
Drug development approach: Cotadutide (AstraZeneca), a balanced GLP-1R/glucagon-R co-agonist derived from OXM structure, is the primary translational tool at 100-300 mcg SC/week
Administration in Research Settings
Standard reconstitution and administration methodology for laboratory research use.
Used as a research reference standard in metabolic studies. Requires IV or SC infusion. The native peptide's short half-life necessitates continuous delivery systems or use of long-acting analogues for sustained studies.
What the research doesn't show
Oxyntomodulin has a short half-life (like native GLP-1) and isn't practical as a drug itself. All the clinical data comes from short infusion studies, not long-term treatment. The pure glucagon receptor stimulation angle also raises questions: glucagon raises blood glucose, which is counterproductive in diabetics. Achieving the metabolic benefits of glucagon agonism without the hyperglycemia risk is the engineering challenge the synthetic dual agonists are trying to solve.
Medical Expert Videos
Physicians, researchers, and pharmacologists explain Oxyntomodulin, covering mechanisms of action, clinical context, and study findings.
Videos sourced from YouTube search. KnowYourPeptide does not endorse any individual creator. For research education only.
The Bottom Line
Oxyntomodulin has a growing body of preclinical evidence and a well-characterised safety profile in research settings. The most-studied application is: dual glp-1r and glucagon receptor agonism — suppresses appetite (glp-1r) while increasing energy expenditure (glucagon-r).
The most commonly reported side effect in research subjects is nausea and vomiting due to glp-1r component. It is a research chemical, not approved for human use.
Frequently Asked Questions
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How It Compares
Oxyntomodulin is the natural model for what drug developers are now engineering: cotadutide (GLP-1/glucagon dual agonist from AstraZeneca) and similar synthetic dual agonists are essentially stabilized, potentiated versions of oxyntomodulin's biology. Tirzepatide goes a different direction (GLP-1 + GIP). Among the natural gut peptides, oxyntomodulin is one of the more interesting from a drug design standpoint because it demonstrates the dual-agonism concept already works in nature.
Compare Oxyntomodulin side-by-sideResearch Use Only
This information is for educational research purposes only. This is not medical advice. Consult a qualified healthcare professional.