Apraglutide

FE 203799, apraglutide (INN)

Recovery, repair & tissue

Awaiting medical reviewEN ES DE FR PT ZH+ Follow for updates

Summary

Class: Synthetic long-acting GLP-2 (glucagon-like peptide-2) analogue, 33 amino acids, modified for protease resistance and high albumin affinity
Mechanism: Activates the GLP-2 receptor in the gut to increase villus height, mucosal surface area and nutrient absorption, so people on intravenous nutrition can reduce it
Routes studied: Subcutaneous once weekly
Half-life: Substantially longer than native GLP-2 (which is cleared in minutes) — supports once-weekly dosing; exact human figure not stated here †
Storage: Investigational product supplied and handled under trial protocol; no consumer formulation exists
Regulatory status: Not approved anywhere. Orphan designations granted in US and EU; FDA has indicated a confirmatory Phase 3 trial is needed before approval

Doses are as reported in studies or by the community — never recommendations.

1What it is

Apraglutide is a synthetic analogue of GLP-2, a hormone released by specialised cells in the intestinal lining after eating. GLP-2's natural job is to keep the gut lining in good repair and to expand absorptive surface when there is food to absorb. In short bowel syndrome with intestinal failure (SBS-IF) — where surgical removal of intestine leaves too little absorptive surface — people depend on parenteral support, meaning nutrition and fluid delivered intravenously, often for several nights a week for life. A GLP-2 analogue that increases absorption can reduce that dependence.

Native GLP-2 is destroyed within minutes by the enzyme DPP-4. Apraglutide is engineered for DPP-4 resistance and strong albumin binding, which is what allows once-weekly rather than daily injection. That is its main point of difference from teduglutide (#164), the approved daily GLP-2 analogue. It is an investigational drug; it has never been marketed.

2How it's thought to work

GLP-2 receptor activation in the intestine. triggers release of local growth mediators (IGF-1, keratinocyte growth factor, nitric oxide) from subepithelial cells, which in turn drive crypt cell proliferation.

Structural effect. villi lengthen, crypts deepen, and absorptive surface area increases. Transit slows and intestinal blood flow rises.

Functional effect. more fluid, electrolytes and nutrients are absorbed enterally, so the volume needed intravenously falls. In the best responders, parenteral support can be stopped entirely ("enteral autonomy").

Why weekly matters. daily injection is a substantial burden for this patient group; weekly dosing was the development rationale.

A long-acting GLP-2 analogue dosed weekly rather than daily, with the same effect on intestinal surface area in short bowel syndrome.Schematic — not to scale

3What the research shows

Short bowel syndrome with intestinal failure

STARS, a Phase 3 randomised, double-blind, placebo-controlled trial, is the largest SBS-IF trial conducted to date. The sponsor reported that apraglutide achieved a statistically significant reduction in weekly parenteral support volume versus placebo with once-weekly dosing, and that in the long-term extension 27 patients who had depended on parenteral support reached enteral autonomy (sponsor reports 2024–2025; full peer-reviewed publication should be checked before citing figures). Treat the enteral-autonomy count as a single-arm extension observation, not a controlled endpoint.

Not graded

Regulatory interpretation of STARS — important caveat

In 2025 the sponsor disclosed that, after discussion with the FDA, a confirmatory Phase 3 trial would be required before approval could be sought in parenteral-support-dependent SBS-IF. A pharmacokinetic analysis found the exposure actually delivered in STARS was lower than planned because of how doses were prepared and administered. This is unusual and worth stating plainly: a trial that met its endpoint did not, in the regulator's view, establish an approvable dose.

Earlier clinical pharmacology

Phase 1 and Phase 2 work in healthy volunteers and in SBS established the weekly dosing interval, dose-dependent increases in citrulline (a marker of enterocyte mass) and intestinal absorption signals (Wisniewski 2016, J Pharmacol Exp Ther; Naimi 2019, Lancet Gastroenterol Hepatol †). [1][2]

Graded B/C

Other indications

Exploratory work has looked at graft-versus-host disease of the gut and at acute radiation-induced intestinal injury, on the same mucosal-repair logic. These are early and should not be described as established. Community use: essentially none documented. This is an investigational hospital-administered drug for a rare condition, used only within trials.

4Reported side effects and interactions

Literature-reported

The adverse-effect profile reported in trials is the GLP-2 class profile — abdominal pain and distension, nausea, vomiting, peripheral oedema, stoma complications in people with a stoma (swelling of the stoma, narrowing), and injection-site reactions. Fluid overload can occur when intravenous volume is not reduced as enteral absorption improves.

Community-reported

none; no community use exists.

Theoretical / class-level. GLP-2 analogues are trophic to intestinal mucosa, which raises concern about accelerating existing neoplasia. Teduglutide's label requires colonoscopy before starting and periodically thereafter, and the same logic applies here. Biliary and pancreatic events have been reported with the class and are monitored in trials.

Interactions. improved intestinal absorption can increase absorption of oral medicines, including drugs with a narrow therapeutic margin; doses may need review. Concomitant intravenous fluid and nutrition prescriptions must be actively reduced, which is a prescribing interaction in practice.

Markers researchers commonly monitor

Taken from the GLP-2 class and the SBS-IF trial protocols:

Marker	Why it's watched
Weekly parenteral support volume	the actual endpoint; everything else is supporting data.
Plasma citrulline	a marker of functional enterocyte mass; rises with GLP-2 receptor activation.
Body weight, fluid balance, urine output	to catch fluid overload as enteral absorption improves and intravenous volume has not yet been cut.
Electrolytes, magnesium, creatinine and eGFR	SBS-IF patients run close to the edge on all of these.
Liver function tests and bilirubin	intestinal-failure-associated liver disease is common in this population, and biliary events are a class concern.
Lipase and amylase	pancreatic events are monitored with GLP-2 analogues.
Colonoscopy before and during treatment	mandated for teduglutide because of the mucosal-trophic mechanism; the same precaution is applied in GLP-2 trials.

Free for everyone. Safety information is never behind a paywall.

5Formulation and administration context

Investigational injection supplied under trial protocol, and administered per that protocol by trained staff or trained patients. There is no marketed presentation, no consumer formulation and no self-preparation guidance. The STARS exposure finding is itself a reminder that preparation and administration detail can change delivered dose materially.

6Commonly studied alongside

Teduglutide (#164) as the approved comparator in the same indication, glepaglutide (#244) as the other weekly/twice-weekly GLP-2 analogue in development, and parenteral nutrition management generally. Also discussed alongside GLP-1 analogues such as semaglutide (#3) only as a matter of receptor-family biology, not as a combination.

Informational cross-links. Not stack recommendations.

7Regulatory status by region

Region	Status (checked —)
United States	Not approved. Orphan drug designation for SBS; FDA has indicated a confirmatory Phase 3 trial is needed before an NDA can be filed. Submission on hold †
European Union	Not authorised; orphan designation granted †
United Kingdom	Not licensed
Australia	Not approved
South Africa	Not registered
Sport	Not specifically listed by WADA; as a non-approved substance it would fall under S0 for athletes. Check the current list

8Open questions

What the correct dose actually is, given the STARS exposure shortfall.
Whether a confirmatory trial reproduces the parenteral-support reduction at the intended exposure.
Whether once-weekly dosing is genuinely as effective as daily teduglutide — no head-to-head trial exists.
Long-term neoplasia risk with sustained GLP-2 receptor activation.

9References

1Wisniewski K et al. (2016). Discovery of a novel, long-acting GLP-2 analog for the treatment of short bowel syndrome. J Pharmacol Exp Ther. PubMed
2Naimi RM et al. (2019). Effects of apraglutide, a novel long-acting GLP-2 analogue, on intestinal absorption in patients with short bowel syndrome. Lancet Gastroenterol Hepatol [verify]. PubMed
3Jeppesen PB et al. (2024–2025). STARS: a Phase 3 trial of apraglutide in short bowel syndrome with intestinal failure. [Publication to be confirmed before citing figures.] PubMed
4Ironwood Pharmaceuticals (2025). Clinical and regulatory update on apraglutide (company disclosure of FDA requirement for a confirmatory Phase 3 trial). PubMed
5Drucker DJ, Yusta B (2014). Physiology and pharmacology of the enteroendocrine hormone glucagon-like peptide-2. Annu Rev Physiol. PubMed · DOI

References are being resolved to PubMed/DOI identifiers; links search PubMed for the citation until then.

† Being confirmed by our reviewers against current sources.

10Community

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Self-reported side effects Phase 2

Not enough data yet. 0 of the 50 members needed have logged this compound for 4+ weeks. We don't show anything below 50, so no one can be identified.

11Page history

31 Oct 2026Profile published — awaiting medical review

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