Evidence memo / Tissue repair & recovery

Apraglutide

Also: long-acting GLP-2 analog

Apraglutide is a long-acting GLP-2 analog being developed for short bowel syndrome in people who depend on parenteral support. It is designed for less frequent dosing than older GLP-2 drugs. It has reached late-stage trials and regulatory review, but it is not a general gut-health peptide. The Watchlist boundary is keeping it to its investigational short bowel syndrome program and the GLP-2 class safety considerations.

Controlled human dataPhase 2 / Phase 3InvestigationalSafety / regulatory watch

The verdict

Our read at a glance.

Whether apraglutide's late-stage short bowel syndrome data support its approval and use in that specific condition, separate from broad gut-repair claims.

The signal
Late-stage trials, including the STARS program, have tested apraglutide for reducing the need for parenteral support in short bowel syndrome. As an investigational drug, its full evidence and regulatory status are still being established.
The unknown
Whether its longer dosing interval translates into a clear benefit over existing GLP-2 therapy, and its long-term safety, including the neoplasia concerns common to the GLP-2 class.
Our read
A next-generation GLP-2 drug for a serious condition, still investigational. Apraglutide's short bowel syndrome program is advanced, but until approval and full data it should be read as investigational, not established.

The mechanism

How it works.

Apraglutide is a long-acting analog of glucagon-like peptide-2 (GLP-2), the hormone intestinal cells release after eating to maintain the gut lining. It binds the GLP-2 receptor on cells in the intestinal wall, which stimulates the lining to grow, increases blood flow, and expands its capacity to absorb nutrients and fluid. In short bowel syndrome the goal is to enlarge that absorptive surface enough to reduce reliance on intravenous nutrition, and its amino-acid changes are meant to extend its action so it can be dosed less often than earlier GLP-2 drugs. This is being tested in late-stage trials and apraglutide is not yet an approved product.

Safety & regulatory boundary

The consequential part.

Apraglutide is investigational and not an approved product in general use during this period. GLP-2 analogs as a class carry concerns about promoting growth, including potential neoplasia and intestinal effects, which any approval would address through monitoring. Research-labeled or compounded apraglutide is not an approved product, and its development status does not support use outside trials.

What's next

What we're watching.

Regulatory decisions, published Phase 3 results, and long-term safety and neoplasia surveillance.

Context

Why this is discussed.

Apraglutide is a leading next-generation GLP-2 analog, of interest to short bowel syndrome patients and as part of the broader GLP-2 story.

The evidence base

20 cited references.

Registered trials8

Proof-of-concept Trial of Apraglutide in Acute Graft Versus Host Disease (aGVHD)

ClinicalTrials.gov · PHASE2 · TERMINATED · 2022-05-25

A Phase 1 Open-Label Evaluation of the Pharmacokinetics and Safety of a Single Dose of Apraglutide in Subjects With Normal and Impaired Hepatic Function

ClinicalTrials.gov · PHASE1 · COMPLETED · 2023-01-30

Open-label Extension Trial to Evaluate the Long-term Safety of Apraglutide in Short Bowel Syndrome.

ClinicalTrials.gov · PHASE3 · ACTIVE_NOT_RECRUITING · 2021-07-13

Metabolic Balance Study of Apraglutide in Patients With Short Bowel Syndrome, Intestinal Failure (SBS-IF) and Colon-in-Continuity (CIC)

ClinicalTrials.gov · PHASE2 · COMPLETED · 2021-06-14

Trial to Evaluate Efficacy and Safety of Apraglutide in SBS-IF

ClinicalTrials.gov · PHASE3 · COMPLETED · 2021-01-26

Study of Pharmacokinetics and Safety of Apraglutide in Participants With Normal and Impaired Kidney Function.

ClinicalTrials.gov · PHASE1 · COMPLETED · 2020-12-08

Relative Bioavailability of a New Presentation of Apraglutide Versus the Reference Formulation

ClinicalTrials.gov · PHASE1 · COMPLETED · 2023-05-23

Safety, Tolerability, PK/PD of FE 203799 in Adults With Lymphomas

ClinicalTrials.gov · PHASE1/PHASE2 · WITHDRAWN · 2018-09-01

Indexed literature (PubMed)12

Use of glucagon-like polypeptide 2 analogs for intestinal failure

Goldschmidt ML et al. · Expert Opin Pharmacother · 2024

Apraglutide, a novel glucagon-like peptide-2 analog, improves fluid absorption in patients with short bowel syndrome intestinal failure: Findings from a placebo-controlled, randomized phase 2 trial

Eliasson J et al. · JPEN J Parenter Enteral Nutr · 2022

Intestinal adaptation and rehabilitation in adults with short bowel syndrome

Pironi L · Curr Opin Clin Nutr Metab Care · 2024

Characterization of the Pharmacokinetic and Pharmacodynamic Profile of Apraglutide, a Glucagon-Like Peptide-2 Analog, in Healthy Volunteers

Bolognani F et al. · J Pharmacol Exp Ther · 2023

Positive clinical outcomes associated with use of glucagon-like peptide-2 (GLP-2) analogues in patients with intestinal failure: A systematic review and meta-analysis

Bastas A et al. · Clin Nutr ESPEN · 2026

Pathophysiology of gastrointestinal acute graft-versus-host disease and the potential role of glucagon-like peptide 2

Zeiser R et al. · Br J Haematol · 2023

Emerging novel therapies for steroid-refractory acute graft-versus-host disease: recent advances and future directions

Ye Y et al. · Curr Opin Immunol · 2025

Emerging drugs for the treatment of short bowel syndrome

Frau T et al. · Expert Opin Emerg Drugs · 2024

Glucagon-like peptide-2 analogues for Crohn's disease patients with short bowel syndrome and intestinal failure

Pizzoferrato M et al. · World J Gastroenterol · 2022

An updated overview of glucagon-like peptide-2 analog trophic therapy for short bowel syndrome in adults

Zhu C et al. · J Int Med Res · 2022

Therapeutic Potential of GLP-2 Analogs in Gastrointestinal Disorders: Current Knowledge, Nutritional Aspects, and Future Perspectives

Kounatidis D et al. · Curr Nutr Rep · 2022

Glucagon-like peptide agonists and use in short bowel syndrome - what about the side effects?

Gorard L et al. · Curr Opin Gastroenterol · 2026

Keep reading

Related published memos.

Thymosin alpha-1RetatrutideTrevogrumabGHK-Cu