Glucagon-Like Peptide-2 (GLP-2) Analogues in Patients With Short Bowel Syndrome Dependent on Parenteral Support: A...

Short bowel syndrome (SBS) is a malabsorptive condition often requiring long-term parenteral support (PS), which is associated with significant complications. Glucagon-like peptide-2 (GLP-2) analogues are shown to enhance intestinal adaptation and reduce PS dependency. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of GLP-2 analogues in adult patients with SBS dependent on PS.

A systematic search of CENTRAL, PubMed, Embase, ClinicalTrials.gov, and Google Scholar was conducted from inception till May 2025. We included randomized controlled trials (RCTs) comparing GLP-2 analogues with placebo in adult SBS patients on stable PS. We analyzed the outcomes using RevMan 5.4, with risk ratio (RR) and mean differences (MD) as the effect measures.

Six RCTs comprising 454 patients were included. GLP-2 analogues significantly reduced PS volume (MD: -251.51 mL/day; 95% CI: -363.93 to -139.08; I ² = 2.5%). The proportion of responders was significantly higher in the treatment group (RR: 1.97; 95% CI: 1.47-2.64), with no significant difference in adverse or serious adverse events between the two groups.

Our meta-analysis found that GLP-2 analogues are effective in reducing PS volume in patients with SBS who are dependent on PS, without an increase in adverse events. However, the current evidence is limited by a small number of early clinical trials, heterogeneity in dosing regimens, and a paucity of data on newer agents like glepaglutide. Further large-scale phase 3 RCTs are needed to validate the safety and efficacy of GLP-2 analogues before they can be adopted for routine clinical practice.