GLP-2 analogues in short bowel syndrome: A systematic review and meta-analysis of randomized controlled trials

Background & aims The efficacy of glucagon-like peptide-2 (GLP-2) analogues in patients with short bowel syndrome (SBS) with intestinal failure (IF) is not well established. We aimed to compare the efficacy of GLP-2 analogues relative to placebo in patients with SBS dependent on parenteral support (PS). Methods PubMed, Embase, and Cochrane Central were searched from inception to April 15, 2025 for randomized controlled trials (RCTs) comparing GLP-2 analogues with placebo in patients with SBS. Endpoints included change in weekly PS volume, clinical response, enteral autonomy, and ≥1-day/week PS reduction. Pooled risk ratios (RRs) and standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated using random-effects models. SMD was used due to differences in reporting units (mL/day vs. L/week). Results We included 283 patients from 4 RCTs, including one crossover trial; 188 (66.4%) received GLP-2 analogues. Weekly absolute PS volume reduction was significantly greater with GLP-2 analogues than with placebo (SMD −0.54; 95% CI −0.71 to −0.36; p = 0.0022; I² = 0%), with consistent results in a sensitivity analysis restricted to week 24. There were no significant differences in clinical response (RR 1.94; 95% CI 0.57 to 6.56; p = 0.1453; I² = 23.7%) and enteral autonomy (RR 4.21; 95% CI 0.00 to 280351.17; p = 0.3479; I² = 0%) between groups. Clinical response was defined as achieving a ≥20% reduction in weekly PS volume from baseline sustained through weeks 20 and 24. Reduction in PS by ≥ 1 day/week was more frequent with GLP-2 analogues (RR 2.27; 95% CI 1.59 to 3.26; p = 0.0219; I² = 0%). Conclusion This meta-analysis of 4 RCTs including 283 patients showed that GLP-2 analogues significantly reduced weekly PS volume and more often achieved ≥1-day/week reductions in PS compared with placebo, with no significant differences in enteral autonomy or clinical response.