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Peptide Profile

Oxyntomodulin

OXM · glicentin-related pancreatic peptide

Oxyntomodulin is an endogenous 37-amino-acid proglucagon-derived peptide co-secreted with GLP-1 and PYY by intestinal L-cells in response to nutrient ingestion, distinguished from GLP-1 by a C-terminal octapeptide extension that…

MetabolicInvestigationalResearch Only
Routes
subcutaneous, intravenous

Educational research information — not medical advice. Review primary sources and consult a qualified professional before any decision.

Educational research tools — not medical advice.

Overview

What Oxyntomodulin is

About Oxyntomodulin

Dual GLP-1/glucagon receptor agonist. GLP-1 component suppresses appetite; glucagon component increases energy expenditure and fatty acid oxidation. Net effect is reduced caloric intake and elevated metabolic rate.

Oxyntomodulin is an endogenous 37-amino-acid proglucagon-derived peptide co-secreted with GLP-1 and PYY by intestinal L-cells in response to nutrient ingestion, distinguished from GLP-1 by a C-terminal octapeptide extension that enables dual agonism at both the GLP-1 receptor and the glucagon receptor, producing combined effects on appetite suppression, energy expenditure, and glucose homeostasis. GLP-1 receptor activation by oxyntomodulin reduces food intake through central satiety signaling, while concurrent glucagon receptor activation stimulates hepatic glucose production, thermogenesis in brown adipose tissue, and elevated energy expenditure — a combination that theoretically produces greater weight loss than GLP-1 receptor activation alone while the glucogenic and GLP-1 effects approximately offset each other's glycemic impact. A double-blind randomized controlled trial of subcutaneous oxyntomodulin in overweight and obese human subjects demonstrated significant body weight reduction versus placebo over a 4-week treatment period, establishing proof-of-concept for dual GLP-1/glucagon receptor co-agonism as a human anti-obesity mechanism and validating the pharmacological rationale for long-acting dual agonist drug development programs. Native oxyntomodulin has no FDA approval; its short plasma half-life from DPP-IV degradation precludes clinical development in its native form, and commercial research interest has shifted to stabilized long-acting dual agonist analogs such as cotadutide, survodutide, and mazdutide, which use this dual GLP-1/glucagon mechanism in engineered molecules with drug-like pharmacokinetics; mazdutide, an oxyntomodulin analog, received its first regulatory approval (China, 2025). The more recent retatrutide extends the concept to a triple GIP/GLP-1/glucagon agonist rather than a pure dual agonist.

Oxyntomodulin Benefits & Research Areas

appetite suppressionenergy expenditurefat oxidation
The Research

What the evidence says about Oxyntomodulin

Research Evidence

Established Clinical

based on 11 studies · 4 RCTs · most recent 2026

Regulatory Status

Availability Status
Research Only
FDA Status
Investigational

Regulatory status reflects publicly available information and may change. This is not legal or medical advice.

Research Sources

11 sources cited · 4 strong · 7 moderate

4 RCTs · 6 Cohorts · 1 Review

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

    Appetite · 2026

    RCTStrongPMID 41833829
  • Effects of acute moderate-intensity continuous running on circulating oxyntomodulin concentrations in healthy men and women.

    Appetite · 2026

    RCTStrongPMID 41833829
  • Effects of acute moderate-intensity continuous running on circulating oxyntomodulin concentrations in healthy men and women.

    Appetite · 2026

    RCTStrongPMID 41833829
Show 8 more sources
  • Oxyntomodulin reduces energy intake and adiposity in overweight and obese subjects

    Diabetes · 2005

    Research in a 4-week randomized controlled trial found that subcutaneous oxyntomodulin injections three times daily before meals reduced body weight by 2.3 kg compared with 0.5 kg for placebo in overweight and obese adults, associated with a significant reduction in energy intake and increased energy expenditure.

    RCTStrongPMID 16046306
  • Regulators of Appetite in Mammals - Old and New players.

    Endocr Rev · 2026

    CohortModeratePMID 42274231
  • Regulators of Appetite in Mammals - Old and New players.

    Endocr Rev · 2026

    CohortModeratePMID 42274231
  • Patent landscape and therapeutic evolution of mazdutide: a dual GLP-1/Glucagon receptor agonist for obesity and type 2 diabetes.

    Expert Opin Ther Pat · 2026

    # Summary Research found that mazdutide, a dual GLP-1/glucagon receptor agonist, is protected by a comprehensive patent strategy spanning molecular composition, manufacturing processes, formulation technologies, and multiple therapeutic applications for obesity and type 2 diabetes. This study demonstrated how layered intellectual property approaches combining peptide design, formulation innovation, and clinical use claims create sustained market exclusivity for next-generation incretin-based therapeutics.

    ReviewModeratePMID 41820018
  • Distinctive patterns of glucagon and incretin responses to oral and isoglycaemic intravenous glucose load in fibrocalculous pancreatic diabetes.

    Sci Rep · 2026

    CohortModeratePMID 42321243
  • Regulators of Appetite in Mammals - Old and New players.

    Endocr Rev · 2026

    CohortModeratePMID 42274231
  • Distinctive patterns of glucagon and incretin responses to oral and isoglycaemic intravenous glucose load in fibrocalculous pancreatic diabetes.

    Sci Rep · 2026

    CohortModeratePMID 42321243
  • Distinctive patterns of glucagon and incretin responses to oral and isoglycaemic intravenous glucose load in fibrocalculous pancreatic diabetes.

    Sci Rep · 2026

    CohortModeratePMID 42321243

Oxyntomodulin Side Effects & Safety Considerations

No FDA-approved label for this compound. Cautions below are extrapolated from its mechanism/drug class — investigational; educational only.

Absolute contraindications

Personal or family history of medullary thyroid carcinoma (MTC)Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)Known hypersensitivity to the drug or excipients

Warnings & cautions

Acute pancreatitisPregnancy (discontinue; not for use in pregnancy)Gallbladder disease / cholelithiasisDiabetic retinopathy complications (reported with GLP-1 receptor agonist use)Severe GI disease / gastroparesis / ileus riskHypoglycemia when combined with insulin or sulfonylureasAcute kidney injury secondary to volume depletion

Class-based (investigational)

Consult a qualified healthcare professional before making any health decisions. This information is educational only and does not constitute medical advice.

Frequently Asked Questions — Oxyntomodulin

Oxyntomodulin is an endogenous 37-amino-acid proglucagon-derived peptide co-secreted with GLP-1 and PYY by intestinal L-cells in response to nutrient ingestion, distinguished from GLP-1 by a C-terminal octapeptide extension that enables dual agonism at both the GLP-1 receptor and the glucagon receptor, producing combined effects on appetite suppression, energy expenditure, and glucose homeostasis. GLP-1 receptor activation by oxyntomodulin reduces food intake through central satiety signaling, while concurrent glucagon receptor activation stimulates hepatic glucose production, thermogenesis in brown adipose tissue, and elevated energy expenditure — a combination that theoretically produces greater weight loss than GLP-1 receptor activation alone while the glucogenic and GLP-1 effects approximately offset each other's glycemic impact.

appetite suppression, energy expenditure, fat oxidation.

Research on Oxyntomodulin primarily documents effects related to appetite suppression and energy expenditure and fat oxidation. These are areas covered in preclinical and clinical literature — individual response varies and effects depend on context of use.

Reported contraindications and considerations for Oxyntomodulin include Personal or family history of medullary thyroid carcinoma (MTC), Multiple Endocrine Neoplasia syndrome type 2 (MEN 2), Known hypersensitivity to the drug or excipients. 7 additional considerations are noted in the safety profile above. This is educational information only — consult a qualified healthcare professional before use.

For Oxyntomodulin, its FDA status is investigational (not FDA-approved), and it is designated for research use only. Regulatory status reflects publicly available information and may change. This is not legal or medical advice.

Research in a 4-week randomized controlled trial found that subcutaneous oxyntomodulin injections three times daily before meals reduced body weight by 2.3 kg compared with 0.5 kg for placebo in overweight and obese adults, associated with a significant reduction in energy intake and increased energy expenditure.

Access

How to get Oxyntomodulin

Where to buy Oxyntomodulin

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