Introduction

Glucagon-like peptide-2 (GLP-2) analogs stimulate adaptation of the remaining gut of patients with short bowel syndrome and intestinal failure (SBS-IF), resulting in increased intestinal absorption. Overall, preclinical data suggest intestinal permeability may be compromised in patients with SBS, which may contribute to fluid losses. However, it remains unclear whether this can be improved by GLP-2 analog treatment.

Aims & Methods

STARS Nutrition was a 52-week multicenter, open-label, phase 2 study in adult patients with SBS-IF and a colon-in-continuity (CiC) (Leuven n=7, Paris n=2) receiving weekly subcutaneous injections with the novel, long-acting GLP-2 analog apraglutide. Duodenal and sigmoid colon biopsies were collected at screening, 24 weeks, and 48 weeks of treatment. Ussing chamber experiments were performed (Leuven only) to measure the transepithelial electrical resistance (TEER) and passage of a 4 kDA fluorescently-labelled dextran molecule (FITC-D4). In addition, qRT-PCR experiments were performed for genes of tight junction- and intercellular adhesion-related proteins. Data are presented as median (min – max). Nominal p-values are calculated using Wilcoxon matched-pairs signed rank tests (significance ≤0.05).

Results

The baseline colonic TEER of 21.56 (12.50 – 28.33) Ω.cm² significantly increased to 27.22 (22.78 – 32.67) Ω.cm² (p=0.0156) at 48 weeks. In addition, the baseline FITC-D4 flux of 34.75 (19.35 – 59.03) pmol was significantly reduced to 17.42 (10.03 – 45.28) pmol (p=0.0469) at 48 weeks. There were no significant changes in gene expression in the duodenum or sigmoid colon.

Conclusion

Apraglutide in SBS-IF-CiC led to significantly improved colonic permeability, potentially contributing to its pro-adaptive effect.

Disclosure

This research was supported by VectivBio, now part of Ironwood Pharmaceuticals.

Astrid Verbiest, Joran Toth, Pauline Huyghe, Lise De Meyere, Lucas Wauters, Ricard Farré: no disclosures.
Palle Bekker Jeppesen: PBJ has received grants/research support/honoraria or consultation fees from Albumedix A/S, ArTara Therapeutics, Bainan Biotech, Baxter, Coloplast, Ferring, Fresenius Kabi, GLyPharma, Naia Pharma, NPS Pharmaceuticals, Shire, Takeda, The Novo Nordisk Foundation, Therachon, VectivBio and Zealand Pharma.
Francisca Joly: FJ has received grants/research support/honoraria or consultation fees from Baxter, Fresenius Kabi, Nestlé Health Sciences, BBraun, Theradial, Mayoli, Biocodex, mobile3e Consulting, Carembouche, NPS Pharmaceuticals, Shire, Takeda, Therachon, VectivBio and Zealand Pharma.
Tim Vanuytsel: TV has served on the speaker bureau for Fresenius Kabi, Remedus, Takeda, and VectivBio. TV has provided clinical advice to Baxter, Shire, Takeda, VectivBio, Zealand Pharma. TV has received research grants from Takeda and VectivBio.