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Four substitutions in the GLP-2 backbone — including an aminocaproic-acid residue in place of a lysine — stretch the hormone's minutes-long half-life to a once-weekly schedule.
Also known as: FE 203799 · FE-203799
Part of the Metabolic & GLP-1 peptides cluster
Overview
Apraglutide (FE 203799) is a synthetic 33-amino-acid analogue of glucagon-like peptide-2 with four substitutions (Ala2→Gly, Met10→Ahx, Asn11→D-Phe, Asn16→Leu) that resist proteolysis and support once-weekly subcutaneous dosing. In a 52-week phase 2 study in short bowel syndrome with intestinal failure and colon-in-continuity, parenteral support volume fell 52%. It is in phase 3 and not approved as of September 2026.
Source & context
Biological / chemical source: Synthetic engineered peptide (originated at Ferring; developed by VectivBio, then Ironwood)
Primary research or clinical context: Investigational — phase 3 for short bowel syndrome with intestinal failure; a graft-versus-host disease trial was terminated
What apraglutide is
Apraglutide is a synthetic 33-amino-acid analogue of glucagon-like peptide-2, the intestinal hormone that drives adaptation and growth of the gut lining. Originated at Ferring under the code FE 203799 and later developed by VectivBio and Ironwood, it was designed for once-weekly subcutaneous injection in short bowel syndrome with intestinal failure, where patients depend on intravenous parenteral support. The IUPHAR record also notes investigation in graft-versus-host disease and a withdrawn chemotherapy-toxicity study. As of September 2026 it is in phase 3 and not approved anywhere.
Structure: four changes to GLP-2
Apraglutide keeps GLP-2's 33-residue length and alters four positions: alanine 2 to glycine, methionine 10 to aminocaproic acid (Ahx), asparagine 11 to D-phenylalanine, and asparagine 16 to leucine. According to IUPHAR, the aminocaproic acid in particular reduces degradation by lysine-targeting proteolytic enzymes, and the combination extends circulating half-life enough for weekly dosing. Because the sequence contains non-standard residues (Ahx, a D-amino acid), it is not shown as one-letter chips on this page. In a neonatal piglet model of total ileal resection, apraglutide enhanced adaptation and linear intestinal growth (Hargrove et al., Journal of Pharmacology and Experimental Therapeutics 2020).
Pharmacokinetics
Apraglutide's pharmacokinetic and pharmacodynamic profile was characterised in healthy volunteers (Bolognani et al., Journal of Pharmacology and Experimental Therapeutics 2023), and a single-dose study in people with severely impaired renal function versus healthy controls assessed the risk of over-exposure, since kidney impairment is common in short bowel syndrome (Greig et al., Journal of Clinical Pharmacology 2024). The published abstracts describe the molecule as having a unique, long-acting profile suited to once-weekly dosing; specific half-life values are not stated in the abstracts available for this profile.
Early clinical evidence: absorption and fluid balance
Two small trials established proof of concept. In a placebo-controlled crossover phase 2 study, eight adults with short bowel syndrome intestinal failure received once-weekly 5 mg then 10 mg apraglutide for four weeks each: urine volume — the readout for fluid absorption — increased by an adjusted mean of 714 mL/day and 795 mL/day versus placebo, with no significant difference between doses, and common adverse events were mild to moderate (Eliasson et al., JPEN 2022). In an open-label phase 1/2 study of eight patients on 5 mg weekly, wet-weight absorption rose by 741 g/day and energy absorption by 1,095 kJ/day (Eliasson et al., JPEN 2022).
| Dose (once weekly) | Urine volume change | 95% CI |
|---|---|---|
| 5 mg | +714 mL/day | 490–939 |
| 10 mg | +795 mL/day | 195–1,394 |
52-week phase 2 in colon-in-continuity
A multicentre, open-label 52-week metabolic balance study enrolled nine adults with short bowel syndrome intestinal failure and colon-in-continuity, a subgroup often excluded from GLP-2 trials. Parenteral support volume fell by 4,702 mL/week — 52% — at week 52, and seven of nine patients (78%) achieved at least one day per week off parenteral support. Faecal output was reduced by 253 g/day at four weeks, and at 48 weeks wet-weight absorption rose 316 g/day, energy absorption 1,134 kJ/day and carbohydrate absorption 56.1 g/day. MRI showed small-bowel length increasing from 29.7 to 40.7 cm and duodenal wall thickness increasing by 0.8 mm. Of 127 adverse events, most were mild to moderate (Verbiest et al., Clinical Nutrition 2024).
Status as of September 2026
ClinicalTrials.gov lists a recruiting phase 3 trial comparing apraglutide with a comparator, an active long-term open-label extension, and a terminated phase 2 proof-of-concept trial in acute graft-versus-host disease. No regulatory approval appears in the evidence for this profile. A 2024 network meta-analysis of 23 trials and 843 patients placed apraglutide among the GLP-2 analogues with efficacy data in short bowel syndrome (Sabra et al., Journal of Gastrointestinal Surgery 2024).
Relation to other GLP-2 analogues
Three GLP-2 analogues dominate the literature: the approved daily-dosed teduglutide, glepaglutide (a depot-forming analogue with a hexa-lysine tail, declined by the FDA in 2024) and apraglutide, which reaches weekly dosing through backbone substitutions rather than a tail. The GLP-2 profile covers the hormone; the glepaglutide profile is the closest comparison.
Structure & chemistry
Molecular identity & reference confidence
Source-supported reference
Reference values are taken from the cited molecular record or curated profile. A database match is not independent laboratory verification; modifications, counter-ions, and formulations can change the measured mass.
- Molecular form
- Human GLP-2 (33 residues) with four substitutions: Ala2→Gly, Met10→Ahx (aminocaproic acid), Asn11→D-Phe, Asn16→Leu
- Species
- Not established by this molecular identity audit
- Termini (N / C)
- Not specified / Not specified
Average reference mass
Reference policy updated: 2026-10-05
- IUPHAR/BPS source snapshot · 2026-10-01
- PubChem molecular record · 2026-10-01
- Molecular formula
- C172H263N43O52
- Average reference mass
- ≈ 3,765
- Receptors
- GLP-2 receptor (GLP-2R)
- Backbone
- Human GLP-2 (33 residues) with four substitutions: Ala2→Gly, Met10→Ahx (aminocaproic acid), Asn11→D-Phe, Asn16→Leu
- Status
- Investigational (phase 3, short bowel syndrome). Not approved as of September 2026
Aminocaproic acid (Ahx) replaces a lysine-adjacent position to reduce degradation by lysine-targeting proteases; a D-phenylalanine at position 11 and Gly2 add protease resistance (IUPHAR record).
Chemistry values: curated profile, PubChem, IUPHAR/BPS Guide to Pharmacology · fetched 2026-10-01.
Clinical development snapshot
ClinicalTrials.gov lists 10 registered studies with “Apraglutide” as an intervention (snapshot 2026-09-07). A registry footprint is not evidence of efficacy or approval.
| NCT | Title | Phase | Status | Updated |
|---|---|---|---|---|
| NCT07742735 | A Study to Investigate the Efficacy and Safety of Apraglutide Compared With Placebo in Adult Participants With | Phase 3 | recruiting | 2026-08-04 |
| NCT05415410 | Proof-of-concept Trial of Apraglutide in Acute Graft Versus Host Disease (aGVHD) | Phase 2 | terminated | 2025-10-20 |
| NCT05706623 | A Phase 1 Open-Label Evaluation of the Pharmacokinetics and Safety of a Single Dose of Apraglutide in Subjects | Phase 1 | completed | 2025-07-10 |
| NCT05018286 | Open-label Extension Trial to Evaluate the Long-term Safety of Apraglutide in Short Bowel Syndrome. | Phase 3 | active not recruiting | 2025-07-02 |
| NCT04964986 | Metabolic Balance Study of Apraglutide in Patients With Short Bowel Syndrome, Intestinal Failure (SBS-IF) and | Phase 2 | completed | 2025-06-18 |
| NCT04627025 | Trial to Evaluate Efficacy and Safety of Apraglutide in SBS-IF | Phase 3 | completed | 2024-11-27 |
Apraglutide — reconstitution calculator
Enter how much peptide is in the vial and how much diluent (e.g. bacteriostatic water) is added. The tool returns the resulting solution concentration — and, for any amount you type, the volume it corresponds to. This is educational arithmetic, not a dosing recommendation.
Reference form: Human GLP-2 (33 residues) with four substitutions: Ala2→Gly, Met10→Ahx (aminocaproic acid), Asn11→D-Phe, Asn16→LeuAverage reference mass: 3,765 Da
Enter an amount to see the volume it corresponds to.
Educational concentration mathematics only. This tool does not recommend a dose, amount, or protocol, and nothing here is medical advice. Many peptides are not authorized by Health Canada for human use — see our reconstitution and bacteriostatic-water guides for context.
Change log
Dated observations from the data pipeline (registry flags, trial footprints, identifiers) and editorial reviews of this profile.
- IdentifiersCross-linked to IUPHAR ligand 10685 and PubChem CID 155559189.
- TrialsClinicalTrials.gov snapshot added: 10 registered studies, highest phase 3.
- EditorialProfile content reviewed and updated by the editorial team.
FAQ about Apraglutide
What is Apraglutide?+
Apraglutide (FE 203799) is a synthetic 33-amino-acid analogue of glucagon-like peptide-2 with four substitutions (Ala2→Gly, Met10→Ahx, Asn11→D-Phe, Asn16→Leu) that resist proteolysis and support once-weekly subcutaneous dosing. In a 52-week phase 2 study in short bowel syndrome with intestinal failure and colon-in-continuity, parenteral support volume fell 52%. It is in phase 3 and not approved as of September 2026.
What Canadian product status is recorded for Apraglutide?+
Canadian product status for Apraglutide has not been verified in this profile. No verified record here does not mean no authorization exists. Status depends on the product, formulation and use; consult Health Canada's product records.
What is the typical length of Apraglutide?+
Apraglutide is commonly described as approximately 33 amino acids (GLP-2 analogue).
What is apraglutide?+
A synthetic 33-amino-acid GLP-2 analogue with four substitutions that allow once-weekly injection, in phase 3 development for short bowel syndrome with intestinal failure.
Is apraglutide approved?+
No. As of September 2026 it is investigational, with a phase 3 trial recruiting and no approval in the evidence for this profile.
How much did apraglutide reduce parenteral support?+
In a 52-week open-label phase 2 study of nine patients with colon-in-continuity, parenteral support volume fell 52% (4,702 mL/week) and 78% of patients gained at least one day a week off support.
How does apraglutide differ from GLP-2?+
Four residues are changed — Gly2, aminocaproic acid at 10, D-Phe at 11 and Leu16 — to resist proteases and extend the half-life from minutes to a weekly schedule.
Apraglutide vs glepaglutide?+
Both are long-acting GLP-2 analogues for short bowel syndrome. Glepaglutide uses a hexa-lysine depot tail and twice-weekly dosing; apraglutide uses backbone substitutions for once-weekly dosing.
Related peptides
References & further reading
- 1.Verbiest A et al. (2024). Efficacy and safety of apraglutide in short bowel syndrome with intestinal failure and colon-in-continuity: a multicenter open-label phase 2 trial. Clinical Nutrition
- 2.Eliasson J et al. (2022). Apraglutide, a novel glucagon-like peptide-2 analog, improves fluid absorption in patients with short bowel syndrome intestinal failure. JPEN
- 3.Eliasson J et al. (2022). Apraglutide, a novel once-weekly glucagon-like peptide-2 analog, improves intestinal fluid and energy absorption. JPEN
- 4.Hargrove DM et al. (2020). Pharmacological Characterization of Apraglutide, a Novel Long-Acting Peptidic Glucagon-Like Peptide-2 Agonist. Journal of Pharmacology and Experimental Therapeutics
- 5.Bolognani F et al. (2023). Characterization of the Pharmacokinetic and Pharmacodynamic Profile of Apraglutide in Healthy Volunteers. Journal of Pharmacology and Experimental Therapeutics
- 6.Greig G et al. (2024). Pharmacokinetics and Tolerability of a Single Dose of Apraglutide in Individuals With Impaired Renal Function. Journal of Clinical Pharmacology
- 7.Sabra HK et al. (2024). Efficacy and safety of glucagon-like peptide 2 in patients with short bowel syndrome: a systematic review and network meta-analysis. Journal of Gastrointestinal Surgery