Peptides›Metabolic›GLP-2 (native)

GLP-2 (native)

/ Endogenous 33-residue intestinotrophic gut peptide; cleaved from proglucagon

TIER 1 · ClinicalN = 0 · TESTING PENDINGMW 3766.10 g·mol⁻¹

ALIAS · Glucagon-like peptide-2 · GLP-2 · Native GLP-2(1-33)

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Research use onlyAny dose figures below describe what specific cited studies used, reported factually. Nothing on this page is guidance for human use.READ FIRST →

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§ A · Identity

Primary sequenceHADGSFSDEMNTILDNLAARDFINWLIQTKITD

MW · 3766.10CLASS · Endogenous 33-residue intestinotrophic gut peptide; cleaved from proglucagonCATEGORY · Metabolic

Tier 1 by translational completeness — the native peptide is endogenous and is the founding pharmacology for the approved analog. The native 33-residue GLP-2 peptide itself is not an FDA-approved therapeutic; teduglutide (Gattex / Revestive), the long-acting Gly2-substituted analog, is FDA-approved for short bowel syndrome. The native peptide is widely used in research and as an endogenous biology reference.

§ B · Mechanism of action

GLP-2 is the 33-residue intestinotrophic peptide produced by enteroendocrine L cells through proglucagon processing — the same precursor that produces glucagon (in pancreatic alpha cells) and GLP-1 (in L cells). GLP-2 binds the GLP-2 receptor (GLP-2R), a class B G-protein-coupled receptor expressed on enteric neurons, subepithelial myofibroblasts, and certain enteroendocrine cells, and signals through cAMP. Downstream effects include increased crypt cell proliferation, villus height, intestinal blood flow, and barrier function, and decreased epithelial apoptosis and gastric emptying. Native GLP-2 has a circulating half-life of approximately 7 minutes, limited by DPP-4 cleavage at the N-terminal Ala2; the Gly2 substitution in teduglutide eliminates DPP-4 cleavage and extends half-life to approximately 2 hours.

§ C · Human clinical evidence

Tier 1 for the molecular pharmacology and Tier 1 by analog. The original GLP-2 discovery (Drucker and colleagues, PNAS 1996) demonstrated the intestinotrophic activity of recombinant GLP-2 in mouse models, defining the molecule as a candidate therapeutic for short bowel syndrome. Subsequent human pharmacology studies of native GLP-2 infusion have confirmed intestinal effects but the short half-life limits therapeutic application — teduglutide was developed specifically to address this pharmacokinetic limitation. The Drucker (Annual Review of Physiology 2006) review consolidated the GLP-2 biology field.

§ D · Primary literature

PubMed8755576Drucker DJ et al. — Induction of intestinal epithelial proliferation by glucagon-like peptide 2 · Proceedings of the National Academy of Sciences of the United States of America · rodentRecombinant GLP-2 administration in mice induced selective small bowel epithelial proliferation, increased villus height, and increased mucosal mass — the founding observation of the intestinotrophic pharmacology that informed teduglutide development.Limitations: Rodent only; established the molecule as a candidate therapeutic but did not characterise human pharmacology.1996

PubMed24161075Drucker DJ et al. — Physiology and pharmacology of the enteroendocrine hormone glucagon-like peptide-2 · Annual Review of Physiology · reviewComprehensive review of GLP-2 endocrine physiology, GLP-2 receptor signalling, intestinal trophic and barrier effects, and the translational path from native peptide to teduglutide and longer-acting analogs.Limitations: Narrative review; not a quantitative synthesis of clinical trial outcomes.2014

§ F · Safety signal

Native GLP-2 has not been developed as a therapeutic, so a formal safety database does not exist for the native peptide. Class concerns about chronic intestinotrophic action — particularly the theoretical risk of accelerating malignancy growth in tissues with pre-existing dysplasia — apply to the analog teduglutide and feature in its labelling. Native GLP-2 in research contexts has not raised acute safety concerns at studied infusion rates.

§ H · Regulatory status

Regulatory status

FDA status:: Not FDA-approved

§ I · Notable gaps and controversies

The vendor research-chemical 'GLP-2' is the native short-half-life peptide and is not pharmacologically interchangeable with teduglutide (Gattex / Revestive), the FDA-approved analog. Vendor product purity and identity are not regulated to pharmaceutical specification. The therapeutic translation of GLP-2 biology runs through teduglutide and the next-generation longer-acting analog glepaglutide; the native peptide is biological reference, not therapeutic.