Apraglutide
A once-weekly GLP-2 analogue in development to help the remaining gut absorb more in short bowel syndrome
Apraglutide is a long-acting analogue of GLP-2, the gut hormone that makes the intestinal lining grow and absorb, designed for once-weekly injection. It is in development for short bowel syndrome with intestinal failure, where people depend on intravenous parenteral support; no regulator has approved it.
What is it?
Teduglutide, the approved GLP-2 drug, is injected daily; apraglutide aims to do the same job weekly. In small phase 2 studies it raised the fluid, energy and electrolytes the remaining gut absorbed and cut the parenteral support patients needed over a year.
The evidence is still small: metabolic balance studies in single-digit or low double-digit numbers of patients. Pharmacokinetic studies found it does not build up in severe kidney impairment, and a plasma citrulline rise, a marker of enterocyte mass, suggests lasting effects on the gut lining.
Its phase 3 trial, STARS, met its main goal: once a week it reduced parenteral support volume by about a quarter, roughly double the placebo effect, with the clearest benefit in people with a stoma.
STARS, the phase 3 trial, randomised 163 patients, 80 with a stoma and 83 with colon-in-continuity. Weekly parenteral support volume fell 25.5% from baseline against 12.5% on placebo at 24 weeks, and 43.0% of treated patients cut at least one day a week of support against 27.5% on placebo. In the colon-in-continuity group followed to 48 weeks, 51.8% against 44.4% reached that threshold. An earlier year-long metabolic balance study in nine patients with colon-in-continuity had tested the same weekly injection.
The animal work explains the design and its limits. Apraglutide is a GLP-2 agonist with very low clearance, which is what allows weekly rather than daily injection; in mice it lengthened the intestine as well as thickening it, with effects that varied by region and plateaued rather than building with continued dosing. In piglets without an ileum it cut faecal fat and energy losses, and in mice given chemotherapy it improved survival while preserving the gut lining.
Its pharmacology has been mapped in the groups that most often need it. Weekly injections raised plasma citrulline, a marker of enterocyte mass, in a dose-dependent way with lasting effect, and single-dose studies found no overexposure in severe kidney impairment or in mild to moderate liver impairment, so neither required a dose change. A microbiota study found the gut ecosystem in short bowel syndrome already heavily altered; apraglutide did not change overall diversity but reduced the variation between patients, with Bifidobacterium falling and Prevotella rising in some.
Mechanism of Action
Apraglutide is a synthetic GLP-2 analogue designed for once-weekly injection; GLP-2 drives growth and absorptive capacity in the remaining intestine.
Intestinal growth
In animals it increased intestinal weight and length, with taller villi and deeper crypts.
Fluid and energy absorption
In short bowel syndrome it improved fluid and energy absorption and reduced the need for parenteral support.
Very low clearance
Its slow clearance and long half-life are what allow weekly dosing, unlike daily teduglutide.
Published Research
Studies in people read from their PubMed abstracts; apraglutide has no label.
A year in nine patients
In a 52-week open-label phase 2 study of nine adults with short bowel syndrome and colon-in-continuity, weekly apraglutide cut parenteral support needs, added days off support and improved absorption, with 127 mostly mild to moderate adverse events.
Absorption on 5 mg weekly
Once-weekly 5 mg raised absorbed wet weight by 741 g a day and energy by 1,095 kJ a day, with more sodium and potassium absorbed, and was well tolerated.
Fluid absorption
Weekly 5 and 10 mg raised urine output, a marker of absorbed fluid, by 714 and 795 mL a day against placebo, with no significant difference between doses.
Kidney impairment
After a single dose, people with severe renal impairment had lower, not higher, exposure than those with normal kidney function (Cmax 36.9 against 59.5 ng/L).
Pharmacokinetics and citrulline
Weekly subcutaneous apraglutide raised plasma citrulline in a dose-dependent way, suggesting early and enduring effects on enterocyte mass and supporting weekly dosing.
Liver impairment
People with moderate hepatic impairment were not overexposed to a single dose compared with normal liver function, adverse events were mild or moderate, and no dose change appeared necessary for mild or moderate impairment.
The gut microbiota
In short bowel syndrome with colon-in-continuity, apraglutide was associated with early maturation of the intestinal microbial ecosystem, suggesting GLP-2 therapy might be combined with microbiome-targeted strategies.
STARS: the phase 3
In 163 adults with short bowel syndrome and intestinal failure, once-weekly apraglutide cut weekly parenteral support volume by 25.5% against 12.5% on placebo at 24 weeks; 43.0% against 27.5% dropped at least one infusion day a week. In patients with colon-in-continuity the week-48 differences were not significant.
Why it lasts a week
Pharmacological characterisation found apraglutide a potent, selective GLP-2 agonist with extremely low clearance and a prolonged half-life, which its authors argue allows weekly instead of daily injection, unlike teduglutide.
Where the gut grows
In mice, apraglutide increased both intestinal weight and length, with effects that depended on time and on the region of intestine and did not grow further with continued dosing.
Newborn piglets without an ileum
In a neonatal piglet model of short bowel syndrome, weekly apraglutide reduced faecal fat and energy losses and lengthened the intestine with taller villi and deeper crypts.
Protecting the gut through chemotherapy
In mice, adding apraglutide to chemotherapy improved survival and reduced weight loss without affecting white cell counts, preserving gut lining structure and raising plasma citrulline.
Dosing Data
Not approved. Trials gave it by subcutaneous injection once weekly, with 5 mg used in the early absorption studies.
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Side Effects & Contraindications
Reported Side Effects
From the trials.
Contraindications & Cautions
No label exists.
Legal Status
Not approved.
Frequently Asked Questions
?How does it differ from teduglutide?
Both are GLP-2 analogues for short bowel syndrome; teduglutide is approved and injected daily, apraglutide is investigational and designed for weekly dosing.
?Is it approved?
No. It is in development, and Drugs@FDA lists no application.
?What does it change for patients?
In the trials it increased what the remaining gut absorbed and reduced the parenteral support some patients needed.
?Why is apraglutide dosed weekly when teduglutide is daily?
Its clearance is very low and its half-life long. The characterisation study presents that as the difference from teduglutide, the only approved GLP-2 agonist.
?Does apraglutide need a dose change in kidney or liver disease?
Not according to its phase 1 studies. Exposure was no higher in severe kidney impairment or in mild to moderate liver impairment than in people with normal function, and adverse events were mild or moderate.
?What did the phase 3 trial show?
In 163 patients, weekly parenteral support volume fell 25.5% from baseline against 12.5% on placebo at 24 weeks, and 43.0% of treated patients cut at least one day a week of support against 27.5% on placebo.
References
- [clinical-trial] Verbiest A, et al. "Efficacy and safety of apraglutide in short bowel syndrome with intestinal failure and colon-in-continuity: A multicenter, open-label, metabolic balance study." Clin Nutr, 2024;43(12):158-166. PMID: 39461299.
- [clinical-trial] Eliasson J, et al. "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 J Parenter Enteral Nutr, 2022;46(7):1639-1649. PMID: 35233802.
- [clinical-trial] Eliasson J, et al. "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 J Parenter Enteral Nutr, 2022;46(4):896-904. PMID: 34287970.
- [clinical-trial] Greig G, et al. "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." J Clin Pharmacol, 2024;64(6):744-754. PMID: 38465515.
- [clinical-trial] Bolognani F, et al. "Characterization of the Pharmacokinetic and Pharmacodynamic Profile of Apraglutide, a Glucagon-Like Peptide-2 Analog, in Healthy Volunteers." J Pharmacol Exp Ther, 2023;386(2):129-137. PMID: 37316329.
- [clinical-trial] Greig G, et al. "Pharmacokinetics and Safety of Single-Dose Apraglutide in Individuals with Normal and Impaired Hepatic Function: A Phase 1, Open-Label Trial." Clin Pharmacol Drug Dev, 2026;15(1):e70006. PMID: 41545784.
- [pubmed] Ekhlas D, et al. "Early ecological changes in intestinal microbiota with the long-acting GLP-2 analog apraglutide in short bowel syndrome." Clin Nutr ESPEN, 2026;73:103138. PMID: 41903849.
- [clinical-trial] Joly F, et al. "STARS Phase 3 Trial: Once-Weekly Apraglutide Reduces Parenteral Support in Short Bowel Syndrome-Intestinal Failure." Clin Gastroenterol Hepatol, 2026. PMID: 42692160.
- [pubmed] Hargrove DM, et al. "Pharmacological Characterization of Apraglutide, a Novel Long-Acting Peptidic Glucagon-Like Peptide-2 Agonist, for the Treatment of Short Bowel Syndrome." J Pharmacol Exp Ther, 2020;373(2):193-203. PMID: 32075870.
- [pubmed] Martchenko SE, et al. "Site-Specific and Temporal Effects of Apraglutide, a Novel Long-Acting Glucagon-Like Peptide-2 Receptor Agonist, on Intestinal Growth in Mice." J Pharmacol Exp Ther, 2020;373(3):347-352. PMID: 32144124.
- [pubmed] Slim GM, et al. "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 J Parenter Enteral Nutr, 2019;43(7):891-898. PMID: 30614011.
- [pubmed] Minden MD, et al. "The Long-Acting Glucagon-Like Peptide-2 Analog Apraglutide Enhances Intestinal Protection and Survival After Chemotherapy and Allogeneic Transplantation in Mice." Ann Transplant, 2024;29:e945249. PMID: 39497378.
Sources & Citations
Studies were read from their PubMed abstracts; a 2021 comment and its correction on the characterisation paper were noted but not cited. Read October 7, 2026.
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