S3077 Glucagon-Like Peptide Peptide-2 (GLP-2) Agonists for Patients With Short Bowel Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Introduction: Short Bowel Syndrome (SBS) significantly impairs the intestinal absorptive capacity, often resulting in malnutrition, dehydration, and metabolic imbalances. Glucagon-like Peptide-2 (GLP-2) analogs have emerged as a promising therapy, enhancing intestinal absorption in the residual intestine, reducing malabsorption, and decreasing reliance on parenteral support (PS). This systematic review and meta-analysis aimed to assess the safety and efficacy of GLP-2 therapy in patients with SBS who are clinically stable on PS. Methods: We searched various electronic databases, including MEDLINE (via PubMed), Embase, the Cochrane Library, and Clinicaltrials.gov, to retrieve randomized controlled trials (RCTs) comparing GLP-2 agonists to placebo in patients with SBS. We performed a statistical analysis on RevMan 5.4 using the random effect model. We reported dichotomous outcomes as relative risk (RR) along with 95% confidence intervals (CI) and continuous outcomes as mean difference (MD) along with 95% CI. Results: Our meta-analysis of 6 RCTs comprising 470 patients demonstrated that GLP-2 agonists significantly reduced PS volume from baseline compared to placebo (MD -251; 95% CI: -363- -139; I2 = 0%). Subgroup analyses confirmed consistent reductions in PS volume with teduglutide and glepaglutide, but not with apraglutide (MD -93; 95% CI: -344 - 156). Furthermore, GLP-2 agonists nearly doubled the number of responders (defined as a ≥20% reduction in PS volume) compared to placebo (RR 1.97; 95% CI: 1.47, 2.64; I2 = 0%). No significant differences were observed between groups in the rates of adverse events (RR 1.01; 95% CI: 0.94, 1.09) or serious adverse events (RR 1.19; 95% CI: 0.86, 1.63). Conclusion: These findings highlight the efficacy of GLP-2 agonists in reducing PS dependence in patients with SBS, without increasing the risk of adverse events. Further research with large-scale RCTs is warranted to confirm long-term benefits, explore comparative effectiveness among GLP-2 analogues, and their impact on quality of life.