Glucagon-like peptide-2 (GLP-2) is a 33-amino-acid hormone released by enteroendocrine L cells of the distal ileum and colon. Its receptor, GLP-2R, is expressed on enteric neurons and subepithelial myofibroblasts, and signalling through it is the principal driver of the intestinal adaptation that follows resection. Native human GLP-2 is not a practical drug: dipeptidyl peptidase-4 (DPP-4) cleaves it at the alanine in position 2, giving a plasma half-life of roughly seven minutes. Each GLP-2 analogue in development is, at bottom, an answer to that one problem.

One hormone, three half-life strategies

Teduglutide, glepaglutide and apraglutide activate the same receptor. They differ in how much of the native sequence they alter, and therefore in how long they survive in circulation.

Teduglutide replaces the position-2 alanine with glycine, removing the DPP-4 cleavage site. That single substitution extends the terminal half-life to about 3.0–5.5 hours after subcutaneous administration in humans. It is the oldest of the three and the only one holding a UK marketing authorisation.

Glepaglutide carries nine amino-acid substitutions and six lysine residues added at the C-terminus; the resulting molecule has a reported half-life of around 50 hours, which supports less frequent administration. It remains investigational.

Apraglutide is engineered for once-weekly dosing. In preclinical pharmacokinetic work its clearance in rats was markedly lower than teduglutide's, consistent with a longer duration of action.

What the randomised evidence shows

A 2025 systematic review and meta-analysis pooled randomised controlled trials of GLP-2 analogues in adults with short bowel syndrome dependent on parenteral support. Against placebo, the pooled change in parenteral-support volume was −274.79 mL/day in the teduglutide group (95% CI −428.00 to −121.59) and −326.00 mL/day in the glepaglutide group (95% CI −546.79 to −105.21). The apraglutide estimate was smaller and did not reach statistical significance (−94.00 mL/day, 95% CI −344.00 to 156.00). The authors flagged the small number of trials as a limitation.

These are trial endpoints in a defined patient population, reported here as research findings rather than as claims about what any compound does in general use.

The UK regulatory position

Under the Medicines Act 1968 and the Human Medicines Regulations 2012, a substance presented for a medicinal purpose is a medicine and requires a marketing authorisation before it may be sold or supplied for that purpose. GLP-2 analogues are prescription-only medicines in the UK.

Only teduglutide (Revestive) holds a UK marketing authorisation, for short bowel syndrome in patients aged one year and above who are stable after a period of intestinal adaptation. It was authorised through the EMA's centralised procedure and designated an orphan medicine; the Scottish Medicines Consortium accepted it for restricted use within NHS Scotland in 2018. Glepaglutide and apraglutide are investigational and hold no UK marketing authorisation.

That asymmetry is the story of this class in the UK: one licensed member, two late-stage candidates, and a receptor that has been successfully drugged exactly once.

What this means for research

None of the three compounds is a licensed medicine outside its authorised indication, and none is supplied for human use. Material marketed as a research-grade GLP-2 analogue is not a medicine and carries none of the batch release, potency or sterility assurances that a marketing authorisation requires. Research use only.

Evidence grades

On Peptide Data's four-tier scale, teduglutide sits at Moderate — randomised evidence in a defined, licensed indication — while glepaglutide and apraglutide sit at Limited, reflecting smaller and less certain human datasets. The distinction is about the size and quality of the evidence base, not about how promising a compound looks in isolation.

This article is AI-researched and editorially reviewed. It is provided for research and educational purposes only and is not medical advice. Research peptides are not licensed for human consumption in the UK.