P4064 - Glucagon-Like Peptide Peptide-2 (GLP-2) Agonists for Patients With Short Bowel Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Arslan Hyder, MD¹, Ankit Alria, MBBS², Adnan Rafiq, MBBS³, Shajia Khan, MD⁴, Talha Hasan, MBBS⁵, Muhammad Faiq Akram, MBBS⁶, Eshah Fatima Ali, MBBS⁷, Shah Gul Zahra, MBBS⁸, Farheen F.. Vhora, MBBS⁹, Arsalan Niazi, MBBS¹⁰, Uzair Jaffar, MBBS⁸, Huzaifa Ahmad Cheema, MBBS⁸, Adnan Bhat, MD¹¹, Sheharbano Sajid, MBBS¹², Muhammad Sheharyar Warraich, MD¹³
1Dow Medical College, Karachi, Sindh, Pakistan; 2Sawai Man Singh Medical College, Jaipur, Rajasthan, India; 3Hunan Normal University School of Medicine, Multan, Punjab, Pakistan; 4dubai, Dubai, Dubai, United Arab Emirates; 5Hamdard Medical University, Karachi, Sindh, Pakistan; 6Allama Iqbal Medical College, Lahore, Lahore, Punjab, Pakistan; 7Sargodha Medical College, Sargodha, Punjab, Pakistan; 8King Edward Medical University, Lahore, Punjab, Pakistan; 9B.J. Medical College, Ahmedabad, Ahmedabad, Gujarat, India; 10Punjab Medical College, Faisalabad, Punjab, Pakistan; 11University of Florida, Gainesville, FL; 12CMH Lahore Medical College, Lahore, Punjab, Pakistan; 13University of Illinois, Peoria, IL

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 six 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).

Discussion: 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.


Figure: Forrest plot for mean change in PS volume from baseline


Figure: Forrest plot for incidence of adverse events

Disclosures:
Arslan Hyder indicated no relevant financial relationships.
Ankit Alria indicated no relevant financial relationships.
Adnan Rafiq indicated no relevant financial relationships.
Shajia Khan indicated no relevant financial relationships.
Talha Hasan indicated no relevant financial relationships.
Muhammad Faiq Akram indicated no relevant financial relationships.
Eshah Fatima Ali indicated no relevant financial relationships.
Shah Gul Zahra indicated no relevant financial relationships.
Farheen Vhora indicated no relevant financial relationships.
Arsalan Niazi indicated no relevant financial relationships.
Uzair Jaffar indicated no relevant financial relationships.
Huzaifa Ahmad Cheema indicated no relevant financial relationships.
Adnan Bhat indicated no relevant financial relationships.
Sheharbano Sajid indicated no relevant financial relationships.
Muhammad Sheharyar Warraich indicated no relevant financial relationships.

Arslan Hyder, MD¹, Ankit Alria, MBBS², Adnan Rafiq, MBBS³, Shajia Khan, MD⁴, Talha Hasan, MBBS⁵, Muhammad Faiq Akram, MBBS⁶, Eshah Fatima Ali, MBBS⁷, Shah Gul Zahra, MBBS⁸, Farheen F.. Vhora, MBBS⁹, Arsalan Niazi, MBBS¹⁰, Uzair Jaffar, MBBS⁸, Huzaifa Ahmad Cheema, MBBS⁸, Adnan Bhat, MD¹¹, Sheharbano Sajid, MBBS¹², Muhammad Sheharyar Warraich, MD¹³. P4064 - Glucagon-Like Peptide Peptide-2 (GLP-2) Agonists for Patients With Short Bowel Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials, ACG 2025 Annual Scientific Meeting Abstracts. Phoenix, AZ: American College of Gastroenterology.