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GLP-2: The 33-Amino-Acid Gut Hormone That Grows the Intestinal Lining — and the Template for Teduglutide

GLP-2 (glucagon-like peptide-2) is a 33-amino-acid hormone cut from the same precursor as glucagon and GLP-1. Released by the gut after a meal, it thickens the lining of the small intestine and improves absorption. It was shown to do that in 1996. Its one approved copy, teduglutide, treats short bowel syndrome; it is not a weight-loss drug.

Made by the body33 amino acidsNo FDA-approved product of its own (openFDA, 2026-10-03)

Caroline S · Published 2026-10-03

Length

33 amino acids, no disulfide bonds

Sequence

HADGSFSDEMNTILDNLAARDFINWLIQTKITD — residues 146–178 of the 180-residue human proglucagon precursor (UniProt P01275)

Origin

Cut from proglucagon in the L-cells of the lower small intestine and colon, the same precursor that yields glucagon and GLP-1. Its effect on the intestinal lining was reported by Drucker and colleagues in 1996 (PNAS, PMID 8755576).

Last reviewed

2026-10-03

What is it good for?

In the body, maintaining the lining of the small intestine: UniProt's annotation, citing the literature, describes it increasing villus height and crypt-cell growth and reducing mucosal permeability. As a medicine, its value has come only through an altered copy — teduglutide (Gattex, 2012) for short bowel syndrome. It does not share GLP-1's appetite and blood-sugar role.

Illustration: A clear glass Erlenmeyer flask with faint residue and a copper stirring rod on a white lab bench.
Illustration

What it is

GLP-2 is a hormone of 33 amino acids released by the L-cells of the lower small intestine and colon after a meal. UniProt's record for human proglucagon (P01275) gives its sequence: HADGSFSDEMNTILDNLAARDFINWLIQTKITD, with no disulfide bonds and no end cap.

It does not have a gene of its own. It is cut from proglucagon, a 180-residue precursor that carries several hormones in a row:

Piece of proglucagon Residues What it is
Glucagon 53–81 Raises blood sugar; made in the pancreas
GLP-1 98–127/128 Insulin release, slower stomach emptying, fullness
GLP-2 146–178 Growth and upkeep of the intestinal lining

Which hormones a cell makes depends on how it cuts the precursor. The pancreas cuts out glucagon; the gut's L-cells cut out GLP-1 and GLP-2 together, so the two leave the gut side by side.

What it does

The finding that defined GLP-2 came in 1996, and it began by accident. Drucker and colleagues noticed that mice carrying proglucagon-producing tumours had a markedly overgrown small-intestinal lining, traced the effect to GLP-2 — which they described as a 33-amino-acid peptide "with no previously ascribed biological function" — and showed that giving it produced a heavier bowel with taller villi (the finger-like folds that absorb food) within four days (PNAS, PMID 8755576). That was an animal result. UniProt's function annotation now summarises the literature: GLP-2 stimulates intestinal growth, increases villus height and crypt-cell proliferation, reduces cell death in the lining, and decreases mucosal permeability — how leaky the gut wall is.

That makes GLP-2 a different kind of signal from its neighbour. GLP-1 works on insulin, the stomach and appetite; GLP-2 works mainly on the gut wall itself. The GLP-1 drugs sold for diabetes and weight loss do not act on the GLP-2 receptor.

The approved copy

Natural GLP-2 is cleaved in the blood by an enzyme called DPP-4. The medicine built on it changes the spot the enzyme recognises:

  • Teduglutide (Gattex) — GLP-2 with glycine in place of alanine at position 2, approved on 21 December 2012 (NDA203441) for short bowel syndrome, where surgery or disease has left too little intestine to absorb enough food and water. Its label requires colonoscopy, because tissue growth can include polyps.

Where it stands

openFDA's Drugs@FDA returns no application with GLP-2 itself as the active ingredient (2026-10-03). PubMed returns 1,744 records for "glucagon-like peptide 2", 165 tagged as randomised controlled trials, most of them about teduglutide rather than the hormone. The human evidence in this entry therefore belongs to the drug; what GLP-2 does inside a healthy gut is mapped mainly in animals and cell studies.

GLP-2 shares its precursor with glucagon and travels with the gut hormones recorded in GLP-3 and ghrelin. For how the GLP-1 medicines differ from it, GLP1 Ledger's GLP-1 vs GLP-2 page sets the two side by side.

What the research shows

Grows the lining of the small intestine

Mice given GLP-2 showed increased small-bowel weight and villus height (Drucker 1996, PNAS, PMID 8755576); UniProt P01275 function annotation

An altered copy reduces intravenous feeding in short bowel syndrome

Teduglutide's approval and label (Gattex, NDA203441, 2012-12-21) — see this library's teduglutide entry

Is available as an approved US medicine

No. openFDA's Drugs@FDA returns no application with GLP-2 itself as active ingredient (2026-10-03)

Bars show how much of the evidence is in humans, not how well anything works.

Where it stands

In the body

A gut hormone released by intestinal L-cells after a meal, alongside GLP-1.

United States

No FDA application lists GLP-2 itself (openFDA, 2026-10-03). Its analogue teduglutide (Gattex, NDA203441) was approved on 2012-12-21.

Published record

PubMed returns 1,744 records for "glucagon-like peptide 2", 165 tagged as randomised controlled trials (2026-10-03).

Frequently asked questions

What is GLP-2?

Glucagon-like peptide-2 is a 33-amino-acid hormone made in the L-cells of the lower small intestine and colon. It is cut from proglucagon, the same precursor that gives glucagon and GLP-1, and its main known job is maintaining the lining of the small intestine.

What is the difference between GLP-1 and GLP-2?

They come from the same precursor and leave the same gut cells, but act on different receptors. UniProt's annotation describes GLP-1 as a stimulator of glucose-dependent insulin release that also slows stomach emptying; GLP-2 acts mainly on the gut itself, increasing villus height and absorption. The GLP-1 weight-loss drugs do not act on the GLP-2 receptor.

Is there a GLP-2 medicine?

Not of the natural hormone — openFDA lists no such application (2026-10-03). The approved copy is teduglutide (Gattex, 2012) for short bowel syndrome, which changes one amino acid so the molecule lasts longer in the blood.

Does GLP-2 cause weight loss?

It is not used for weight loss and no approved weight-loss drug acts through it. Its recorded role is the opposite direction: helping the intestine absorb more nutrients, which is why its analogue is used in people who cannot absorb enough food.

Why does teduglutide's label require colonoscopy?

Because a hormone that makes intestinal tissue grow can also speed the growth of polyps. The Gattex label calls for colonoscopy before starting and at set intervals afterwards; this library's teduglutide entry records the details.