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phase 2GI & Metabolic

GLP-2

Also known as: Glucagon-Like Peptide-2, GLP-2 (1-33), Intestinotrophic Hormone, Proglucagon 126-158

GLP-2 (Glucagon-Like Peptide-2) is an endogenous 33-amino-acid peptide hormone produced by intestinal L-cells and certain neurons in the brainstem. It is co-secreted with GLP-1 from the proglucagon gene following nutrient ingestion. GLP-2 is the most potent known intestinotrophic factor — it specifically promotes intestinal mucosal growth, enhances nutrient absorption, reduces intestinal permeability, and inhibits gastric acid secretion. Its analog teduglutide (Gattex/Revestive) is FDA-approved for short bowel syndrome.

3 cited references·5 researched benefits

Quick Answer

GLP-2 (Glucagon-Like Peptide-2) is a 33-amino-acid intestinotrophic hormone co-secreted with GLP-1 from intestinal L-cells after meals. It is the body's primary signal for intestinal mucosal growth, enhancing villus height, crypt depth, and nutrient absorptive capacity. Its degradation-resistant analog teduglutide (Gattex) is FDA-approved for short bowel syndrome. GLP-2 research continues for Crohn's disease, intestinal failure, chemotherapy-induced mucositis, and other GI conditions.

Key Facts

Mechanism
GLP-2 acts through the GLP-2 receptor (GLP-2R), a G-protein-coupled receptor expressed on intestinal subepithelial myofibroblasts, enteric neurons, and enteroendocrine cells (but not directly on intestinal epithelial cells in most species). Activation triggers indirect trophic effects through paracrine mediators including IGF-1, keratinocyte growth factor (KGF), ErbB ligands, and vasoactive intestinal peptide (VIP). These downstream signals stimulate crypt cell proliferation, inhibit enterocyte apoptosis, increase villus height and crypt depth, enhance mesenteric blood flow, and improve nutrient transporter expression. GLP-2 also reduces gastric acid secretion and gastric motility, slowing gastric emptying. Native GLP-2 is rapidly inactivated by dipeptidyl peptidase-4 (DPP-4), giving it a half-life of only 7 minutes.
Research Status
phase 2
Half-Life
~7 minutes (native); ~2 hours (teduglutide analog)
Molecular Formula
C₁₅₂H₂₅₂N₄₄O₅₁
Primary Use
GI & Metabolic
Table of Contents

Benefits

  • Most potent known intestinotrophic factor — increases intestinal villus height and mucosal surface area by 50–100% in animal modelsstrong
  • Teduglutide analog (Gattex) reduces parenteral nutrition dependence by 20–100% in short bowel syndrome patientsstrong
  • Reduces intestinal permeability ("leaky gut") by enhancing tight junction protein expressionmoderate
  • Protects against chemotherapy-induced intestinal mucositis in preclinical modelsmoderate
  • Potential therapeutic target for Crohn's disease, improving mucosal healing and reducing inflammationpreliminary

Dosage Protocols

RouteDosage RangeFrequencyNotes
Subcutaneous injection (teduglutide analog)0.05 mg/kgOnce dailyFDA-approved teduglutide (Gattex) dosing for short bowel syndrome. Native GLP-2 is not used therapeutically due to its 7-minute half-life. Teduglutide has an Ala→Gly substitution at position 2 that resists DPP-4 cleavage.
Subcutaneous injection (native GLP-2, research)400–800 mcg3× dailyResearch protocol dosing for native GLP-2. Rapid DPP-4 degradation necessitates frequent dosing. The teduglutide analog is preferred for any clinical application.

Medical disclaimer

Dosage information is provided for educational reference only. Always follow your prescriber's instructions and consult a qualified healthcare provider before starting any peptide protocol.

Side Effects

  • Abdominal distension and bloating — common with intestinal mucosal expansioncommon
  • Injection site reactions (redness, swelling)common
  • Nausea, especially during initiation of therapycommon
  • Intestinal obstruction or stenosis — mucosal overgrowth can worsen pre-existing narrowingserious
  • Theoretical risk of colorectal polyp or neoplasm acceleration — colonoscopy surveillance recommendedserious
  • Fluid overload — improved intestinal absorption can increase fluid retention, requiring diuretic adjustmentcommon

Frequently Asked Questions

How is GLP-2 different from GLP-1?
GLP-1 and GLP-2 are both derived from the proglucagon gene and co-secreted by intestinal L-cells after meals, but they have very different targets and functions. GLP-1 acts primarily on pancreatic beta cells to stimulate insulin secretion and on the brain to reduce appetite — this is the mechanism behind semaglutide and other GLP-1 RA weight loss drugs. GLP-2 acts primarily on the intestine to promote mucosal growth, enhance nutrient absorption, and reduce intestinal permeability. GLP-1 is the metabolic/appetite hormone; GLP-2 is the intestinal repair hormone.
What is the relationship between GLP-2 and teduglutide (Gattex)?
Teduglutide is a GLP-2 analog with a single amino acid substitution (Ala→Gly at position 2) that makes it resistant to DPP-4 enzymatic degradation. This extends the half-life from ~7 minutes (native GLP-2) to ~2 hours (teduglutide), enabling once-daily dosing. Teduglutide is marketed as Gattex in the US and Revestive in Europe, FDA-approved for short bowel syndrome in adults and children who are dependent on parenteral nutrition. It retains the full intestinotrophic activity of native GLP-2.
Can GLP-2 help with leaky gut or inflammatory bowel disease?
GLP-2 has demonstrated ability to reduce intestinal permeability by enhancing tight junction protein expression and promoting mucosal repair in preclinical models. Phase 2 trials of teduglutide in Crohn's disease showed trends toward clinical improvement and mucosal healing, though results were mixed and larger trials are needed. For "leaky gut" specifically, GLP-2 is one of the most scientifically validated intestinal barrier-enhancing agents, though the clinical concept of "leaky gut syndrome" itself remains debated in mainstream gastroenterology.

References

  1. 1
    Glucagon-like peptide-2: a nutrient-responsive gut growth factor and its role in intestinal adaptation(2000)PubMed ↗
  2. 2
    GLP-2 and intestinal disease: biology, physiology, and pharmacology of the GLP-2 receptor(2005)PubMed ↗
  3. 3
    Teduglutide for the treatment of short bowel syndrome: results of a randomized, double-blind, placebo-controlled phase 3 trial(2012)PubMed ↗

Latest Research

Last updated: 2026-02-19