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.
⚠ 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)
What is Oxyntomodulin?
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.
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.
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.
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Research Use Only
This information is for educational research purposes only. This is not medical advice. Consult a qualified healthcare professional.