What Is Apraglutide? Definition and What Research Reports

Apraglutide is a synthetic peptide analog of glucagon-like peptide-2 (GLP-2), a hormone released by enteroendocrine L-cells of the intestine that signals through the GLP-2 receptor. It was designed as a long-acting agonist at that receptor, and researchers characterised it pharmacologically as a novel long-acting peptidic GLP-2 agonist developed in the context of short bowel syndrome (PMID 32075870). In the published literature the compound also appears under its earlier development code, FE 203799, which was used in a neonatal piglet study of short bowel syndrome with total ileal resection (PMID 30614011). This page is for educational purposes only and is not medical advice; consult a licensed physician for any question about a medical condition or a specific compound.

What class of molecule is it?

Apraglutide belongs to the GLP-2 analog class. Native GLP-2 is a 33-amino-acid peptide that is rapidly degraded in circulation, so analogs in this class are modified to resist breakdown and extend exposure. Apraglutide was described in human pharmacology work as a long-acting GLP-2 analog whose pharmacokinetic and pharmacodynamic profile was characterised in healthy volunteers (PMID 37316329), and a separate phase 1 study described it as a novel, long-acting, synthetic GLP-2 analog with what the authors called a unique pharmacologic profile (PMID 38465515). Clinical trial reports have consistently framed it as a once-weekly GLP-2 analog, in contrast to shorter-acting members of the class (PMID 35233802).

Where the term comes from

The name follows the international nonproprietary naming convention for GLP-2 analogs, which share the -glutide stem used across glucagon-family peptide drugs. The molecule originated in pharmaceutical development rather than in academic isolation work, and the earliest peer-reviewed reports using the name described its pharmacological characterisation for short bowel syndrome (PMID 32075870) and its site-specific and temporal effects on intestinal growth in mice (PMID 32144124).

How the term is used in peptide research

In the research literature, "apraglutide" is used in three fairly distinct ways:

• As a named investigational compound in clinical trials of short bowel syndrome with intestinal failure (SBS-IF), where it has been studied from phase 1 through phase 3 (PMID 42692160).
• As a pharmacological tool for probing GLP-2 receptor biology in animals, for example in the mouse study that examined where along the intestine and over what time course intestinal growth responses occurred (PMID 32144124).
• As a comparator or class exemplar when authors discuss long-acting versus short-acting GLP-2 analogs and dosing frequency, a framing used in the open-label phase 1 and 2 metabolic balance trial (PMID 35233802).

Because it is an investigational biologic studied under clinical trial protocols, apraglutide is not a research-chemical-style peptide with an informal literature; essentially all published human data come from sponsored, protocol-driven trials.

What the published literature reports

Animal studies

The earliest work was preclinical. In a neonatal piglet model of short bowel syndrome with total resection of the ileum, the study reported that FE 203799 (apraglutide) enhanced intestinal adaptation and linear intestinal growth (PMID 30614011). In mice, researchers reported site-specific and temporal effects on intestinal growth, meaning the response varied by intestinal segment and by time after administration (PMID 32144124). A later mouse study in a transplantation context reported that the long-acting GLP-2 analog enhanced intestinal protection and survival after chemotherapy and allogeneic transplantation (PMID 39497378), which is a research direction distinct from short bowel syndrome.

Human pharmacology

A study in healthy volunteers characterised the pharmacokinetic and pharmacodynamic profile of apraglutide, including its long-acting behaviour (PMID 37316329). Two further phase 1 studies examined special populations: one reported pharmacokinetics and tolerability of a single dose in individuals with impaired renal function (PMID 38465515), and an open-label phase 1 trial reported pharmacokinetics and safety of single-dose apraglutide in individuals with normal and impaired hepatic function (PMID 41545784). Studies of this kind exist to describe how exposure differs across organ-function groups; they are not efficacy trials.

Clinical studies in short bowel syndrome

Human efficacy work has concentrated on SBS-IF, a condition in which patients depend on intravenous (parenteral) fluid and nutrition because of insufficient intestinal absorption. A placebo-controlled, randomized phase 2 trial reported improved fluid absorption in patients with short bowel syndrome intestinal failure (PMID 34287970). An open-label phase 1 and 2 metabolic balance trial reported that the once-weekly analog improved intestinal fluid and energy absorption in patients with short bowel syndrome (PMID 35233802). A multicenter, open-label metabolic balance study then examined efficacy and safety specifically in SBS with intestinal failure and colon-in-continuity, an anatomical subgroup that behaves differently from patients with an end-jejunostomy (PMID 39461299). Most recently, the STARS phase 3 trial reported that once-weekly apraglutide reduced parenteral support in SBS-IF (PMID 42692160). A separate analysis reported early ecological changes in the intestinal microbiota with the long-acting GLP-2 analog in short bowel syndrome (PMID 41903849).

Tolerability: What Studies Report

Safety and tolerability have been reported alongside pharmacology rather than as standalone publications in the sources summarised here. The multicenter, open-label metabolic balance study was framed explicitly as an assessment of efficacy and safety in SBS-IF with colon-in-continuity (PMID 39461299). The renal-impairment phase 1 study reported pharmacokinetics and tolerability after a single dose (PMID 38465515), and the hepatic-function phase 1 trial reported pharmacokinetics and safety after a single dose (PMID 41545784). Readers who want event-level detail should consult the full texts, since abstract-level summaries do not enumerate individual adverse events.

Limits of the evidence

Several boundaries are worth noting when the term is encountered:

1. The human evidence base is condition-specific. Clinical trials summarised here were conducted in short bowel syndrome with intestinal failure or in phase 1 pharmacology populations, not in general or healthy-use settings (PMID 34287970).
2. Several key trials were open-label. The metabolic balance studies were described as open-label designs, which limits inference compared with blinded, controlled trials (PMID 35233802).
3. Animal findings do not transfer automatically. The transplantation-context survival findings were reported in mice, not in humans (PMID 39497378).
4. Mechanistic questions remain open, including how microbiota changes relate to absorptive outcomes, an area the microbiota analysis described as early ecological change (PMID 41903849).

Nothing on this page describes how any compound should be administered, and no dosing information is provided. This entry summarises what researchers reported in the peer-reviewed sources listed below.

References

• Novel Long-Acting GLP-2 Analogue, FE 203799 (Apraglutide), Enhances Adaptation and Linear Intestinal Growth in a Neonatal Piglet Model of Short Bowel Syndrome with Total Resection of the Ileum (JPEN. Journal of parenteral and enteral nutrition, 2019)
• Pharmacological Characterization of Apraglutide, a Novel Long-Acting Peptidic Glucagon-Like Peptide-2 Agonist, for the Treatment of Short Bowel Syndrome (The Journal of pharmacology and experimental therapeutics, 2020)
• Site-Specific and Temporal Effects of Apraglutide, a Novel Long-Acting Glucagon-Like Peptide-2 Receptor Agonist, on Intestinal Growth in Mice (The Journal of pharmacology and experimental therapeutics, 2020)
• 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 (JPEN. Journal of parenteral and enteral nutrition, 2022)
• Apraglutide, a novel once-weekly glucagon-like peptide-2 analog, improves intestinal fluid and energy absorption in patients with short bowel syndrome: An open-label phase 1 and 2 metabolic balance trial (JPEN. Journal of parenteral and enteral nutrition, 2022)
• Characterization of the Pharmacokinetic and Pharmacodynamic Profile of Apraglutide, a Glucagon-Like Peptide-2 Analog, in Healthy Volunteers (The Journal of pharmacology and experimental therapeutics, 2023)
• Pharmacokinetics and Tolerability of a Single Dose of Apraglutide, a Novel, Long-Acting, Synthetic glucagon-like peptide-2 Analog With a Unique Pharmacologic Profile, in Individuals With Impaired Renal Function (Journal of clinical pharmacology, 2024)
• Efficacy and safety of apraglutide in short bowel syndrome with intestinal failure and colon-in-continuity: A multicenter, open-label, metabolic balance study (Clinical nutrition, 2024)
• The Long-Acting Glucagon-Like Peptide-2 Analog Apraglutide Enhances Intestinal Protection and Survival After Chemotherapy and Allogeneic Transplantation in Mice (Annals of transplantation, 2024)
• Pharmacokinetics and Safety of Single-Dose Apraglutide in Individuals with Normal and Impaired Hepatic Function: A Phase 1, Open-Label Trial (Clinical pharmacology in drug development, 2026)
• Early ecological changes in intestinal microbiota with the long-acting GLP-2 analog apraglutide in short bowel syndrome (Clinical nutrition ESPEN, 2026)
• STARS Phase 3 Trial: Once-Weekly Apraglutide Reduces Parenteral Support in Short Bowel Syndrome-Intestinal Failure (Clinical gastroenterology and hepatology, 2026)