Efficacy and safety of glucagon-like peptide 2 in patients with short bowel syndrome: a systematic review and network meta-analysis

Abstract

Background: Glucagon-like peptide 2 (GLP-2) is a highly conserved enteroendocrine hormone that seems to be a regulator promoting intestinal adaptation. This study aimed to summarize the evidence on the efficacy and safety of exogenous GLP-2 in patients with short bowel syndrome (SBS).

Methods: A database search was performed on PubMed, Web of Science Core Collection, Scopus, Ovid, and the Cochrane Central Register of Controlled Trials in November 2022. Clinical trials on the effect of GLP-2 on patients with SBS were included. The Cochrane Risk of Bias 2 and Risk Of Bias In Non-randomized Studies - of Interventions tools for quality assessment of randomized and nonrandomized trials were used. The extracted data were analyzed qualitatively and quantitatively using a network meta-analysis model.

Results: This study included 23 clinical trials with 843 patients. The patients' ages ranged from 4.0 to 62.4 years. The treatment doses were 0.1, 0.05, and 0.025 mg/kg/day for teduglutide; 5 and 10 mg/week for apraglutide, and 0.1, 1, and 10 mg/day for glepaglutide. The treatment duration ranged from 1 to 32 weeks. Regarding citrulline level, 0.1 mg/kg/day of teduglutide had the highest mean difference (MD; 14.77; 95% CI, 10.20-19.33), followed by 0.05 mg/kg/day (13.04; 95% CI, 9.79-16.2) and 0.025 mg/kg/day (7.84; 95% CI, 2.42-13.26) of teduglutide. In addition, the effect estimate showed significant differences between all teduglutide dose groups and the control group. Different doses of glepaglutide were analyzed to assess the effect on alkaline phosphatase (ALP) levels, in which 0.1 mg/day of glepaglutide showed a significantly higher MD (20.71; 95% CI, 2.62-38.80) than 1 mg/day (the reference) and 10 mg/day (8.45; 95% CI, -10.72 to 27.62) of glepaglutide. However, 0.1 vs 10 mg of glepaglutide has an MD of -14.57 (95% CI, -437.24 to 148.11) for the indirect estimate, whereas 10 mg of glepaglutide has an MD of 8.45 (95% CI, -10.72 to 27.62) for the network estimate. Regarding safety outcomes, there was no significant difference among all teduglutide and apraglutide dose groups compared with the control group. Catheter-related bloodstream infection was the most common adverse event reported with the use of apraglutide, teduglutide, and glepaglutide.

Conclusion: Despite the small number of patients in the included studies and variable follow-up duration, GLP-2 seems to be safe and effective in patients with SBS. GLP-2 showed a positive effect on increasing plasma citrulline level and decreasing ALP level.

Keywords: Glucagon-like peptide 2; Network meta-analysis; Short bowel syndrome; Systematic review.