Efficacy and safety of glucagon-like peptide-2 (GLP-2) in patients with short bowel syndrome; A Systematic Review and Network Meta-analysis.

BACKGROUND: Glucagon-like peptide-2 is a highly conserved enteroendocrine hormone that appears to be a regulator promoting intestinal adaptation. We aim to summarize the evidence on the efficacy and safety of exogenous GLP-2 in patients with SBS. METHODS: We searched PubMed, Web of Science (WoS) core collection, SCOPUS, Ovid, and Cochrane Central Register of Controlled Trials through November 2022. We included clinical trials on the effect of GLP-2 on patients with SBS. Otherwise, the article was excluded. We used the Cochrane Risk of Bias II and ROBINS-I tools for quality assessment of randomized and non-randomized trials. Extracted data were analyzed qualitatively and quantitatively using a network meta-analysis model. RESULTS: We included twenty-three clinical trials with 843 patients. Patients' ages ranged from 4 to 62.4 years. Treatment doses were (0.1, 0.05, and 0.25mg/kg/day) for Teduglutide, (5, 10mg/week) for Apraglutide, and (0.1, 1, 10mg/day) for Glepaglutide. Treatment duration ranged from one to thirty-two weeks. Regarding citrulline level, the result showed that Teduglutide 0.1mg/kg/day had the highest mean difference (MD=14.77, 95% CI [10.20;19.33]), followed by Teduglutide 0.05mg/kg/day and Teduglutide 0.025mg/kg (MD=13.04, 95% CI [9.79;16.29], and (MD=7.84, 95% CI [2.42;13.26]), respectively. Additionally, the effect estimate showed significant differences among all Teduglutide dose groups and control. Different doses of Glepaglutide were analyzed to assess the effect on alkaline phosphatase levels where Glepaglutide 0.1mg/day showed a significantly higher mean difference (MD=20.71, 95% CI [2.62;38.80]) compared to Glepaglutide 1-mg (the reference), and Glepaglutide 10-mg (MD=8.45, 95% CI [-10.72; 27.62]. However, the indirect estimate for Glepaglutide 0.1-mg vs 10-mg has an MD of (-14.57, 95% CI [-437.24; 148.11]. While Glepagutide 10-mg has an MD of (8.45, 95% CI [-10.72; 27.62]) for the network estimate. Regarding safety outcomes, there was no significant difference among all Teduglutide and Apraglutdie dose groups compared to the control. Catheter-related bloodstream infection (CRBSI) was the most common adverse event reported with Apraglutide, Teduglutide, and Glepaglutide. CONCLUSION: Despite the small number of patients in the included studies and variable follow-up duration, GLP-2 seems safe and effective in patients with SBS. GLP-2 showed a positive effect on increasing plasma citrulline level and decreasing alkaline phosphatase level. OTHER: We registered for the study on PROSPERO (CRD42023393589). There was no funding for this review.