S3050 Apraglutide for Short Bowel Syndrome: A Systematic Review

Introduction: Short bowel syndrome (SBS) is a condition where the body cannot absorb enough nutrients and fluids because a large portion of the small intestines is not functioning or missing. This can be due to surgery, congenital defects, or other medical conditions. It may lead to dependence on parenteral support (PS). This study explores the efficacy and safety of apraglutide, a novel long-acting glucagon-like peptide-2 (GLP-2) engineered for once-weekly dosing on fluid/nutrient absorption and PS requirements. Methods: A literature search across PubMed, Embase, and Cochrane identified clinical trials of apraglutide in adult SBS. Data on efficacy outcomes (e.g., PS volume, days off PS, absorption metrics) and safety (adverse events) were extracted from eligible studies. Results: We identified 4 key clinical studies (total N = 180). In a phase II trial (n = 8) in SBS by Eliasson et al, once weekly apraglutide significantly increased urine volume (marker of fluid absorption) vs placebo. Another study by Eliasson et al was an open-label metabolic balance study (n = 8) that showed that 4 weeks of apraglutide significantly increased wet weight fluid absorption by 741 g/day, and energy absorption by 1095 kJ/day. Electrolyte (Na⁺, K⁺) absorption also rose. A 52-week open-label Phase II “metabolic balance” study by Verbiest et al. in 9 adults with SBS showed that apraglutide yielded a mean 52% reduction in weekly PS volume at 52 weeks (−4702 mL/week). Seven of 9 patients (78%) achieved ≥1 day off PS/week by week 5. Significant gains in absorption were documented: at 48 weeks, wet-weight absorption +316 g/day, energy +1134 kJ/day. In the STARS Trial (Phase III). Apraglutide achieved a significant relative change in weekly PS volume at 24 weeks –25.5% reduction in the treatment group vs –12.5% with placebo. A significantly greater proportion of apraglutide treated patients achieved ≥1 additional day off PS at week 24 (43% vs 27.5%). Subgroup analyses demonstrated consistent benefit across age, sex, weight, and remnant bowel length. Conclusion: Trials of apraglutide in SBS consistently show marked improvements in intestinal absorption and meaningful reductions in PS dependence. Across studies, apraglutide was generally well tolerated with an acceptable safety profile. These collective results support apraglutide as a promising once-weekly GLP-2 therapy for SBS.