GLP-2 (Native)

Glucagon-Like Peptide-2 (GLP-2) — Native Intestinotrophic Hormone

Evidence & Status

  • Moderate Evidence
  • Moderate

At a Glance

The naturally produced intestinal hormone that provided the biological basis for the approved drug Teduglutide. Small human studies show native GLP-2 can increase intestinal blood flow and, in a small short bowel syndrome cohort, reduce fecal losses — informative early findings, not evidence of an approved or broadly proven therapy.

Plain English

Researchers study native GLP-2 because it's the body's own signal for maintaining the intestinal lining, and understanding it directly informed the development of Teduglutide, an approved drug for short bowel syndrome. A few small human studies found that giving people native GLP-2 can increase blood flow to the intestines and, in a small group of short bowel syndrome patients treated for two years, reduce fluid loss from the gut — promising but based on small numbers of people. Teduglutide itself, not native GLP-2, is the approved treatment.

Overview

GLP-2 (glucagon-like peptide-2) is a 33-amino-acid intestinotrophic hormone co-secreted with GLP-1 from L-cells of the distal small intestine and colon; both are derived from proglucagon. GLP-2 binds the GLP-2 receptor (GLP2R) on intestinal enteroendocrine cells, subepithelial myofibroblasts, and enteric neurons. In a small (n=10) acute human infusion study, native GLP-2 increased superior mesenteric artery blood flow relative to saline (Bremholm et al., 2009) — a brief, non-therapeutic physiology finding. In a small short bowel syndrome (SBS) cohort (11 patients, 8 completers) treated with native GLP-2 (400 mcg SC three times daily) for two years, fecal wet weight was reduced and fluid/electrolyte absorption was maintained in completers, with transient abdominal discomfort in about half (Jeppesen et al., 2009 — two companion reports on outcomes and safety/QoL). Teduglutide, an FDA-approved DPP-4-resistant GLP-2 analog for short bowel syndrome, is a distinct approved drug product; its approval does not extend to native GLP-2. This entry provides the mechanistic context for understanding teduglutide's design.

Research Summary

GLP-2 is one of the proglucagon-derived peptides (with GLP-1 and glucagon), discovered as an intestinotrophic hormone by Daniel Drucker's group. Direct human evidence for native GLP-2 is modest in scale: a small acute-infusion study in healthy volunteers showed increased intestinal blood flow, and a small (11-patient) short bowel syndrome cohort treated for two years with native GLP-2 showed reduced fecal losses and maintained absorption in the 8 patients who completed the study, alongside transient GI discomfort in about half. These are small, largely uncontrolled human studies — informative but not sufficient to establish native GLP-2 as an approved or broadly effective therapy. The clinically approved therapy in this space, teduglutide (a DPP-4-resistant GLP-2 analog), is a distinct drug product developed using the mechanistic insight from native GLP-2 research; its approval and outcomes data do not transfer to native GLP-2 itself.

Research Areas

  • Intestinal adaptation
  • Short bowel syndrome
  • Gut mucosal health
  • Intestinal permeability
  • Inflammatory bowel disease
  • GLP-2 receptor pharmacology

Safety & Risks

Serious Risks

  • Not applicable as standalone compound; see Teduglutide entry for therapeutic risk profile

Reported Side Effects

  • At supraphysiologic infusion doses: intestinal hypertrophy, transient GI symptoms
United States
Endogenous hormone — not an approved drug; Teduglutide (Gattex) is the FDA-approved DPP-4-resistant GLP-2 analog
United Kingdom
Not a licensed drug; Teduglutide (Revestive) is the approved analog
Australia
Not a therapeutic product; Teduglutide is TGA-approved
Canada
Not a drug; Teduglutide is Health Canada-approved

Citations & Sources