Background: Dipeptidyl peptidase 4 (DPP-4) inhibitors are a popular second-line treatment for type 2 diabetes mellitus. Several studies have reported on the association between DPP-4 inhibitors and the risk of developing inflammatory bowel disease (IBD), with conflicting results. Objective: This meta-analysis aims to elucidate the risk for IBD with DPP-4 inhibitor therapy. Methods: A comprehensive search of PubMed/MEDLINE, CINAHL, the Cochrane Database, ClinicalTrials.gov, and the European Clinical Trials Database was performed (December 2018). All controlled clinical trials and observational studies of DPP-4 inhibitors that reported events of IBD, Crohn’s disease (CD), ulcerative colitis (UC) or colitis and had a duration ≥52 weeks were included. The DerSimonian and Laird random-effects model was utilized to assess the relative risk (RR) for IBD post DPP-4 inhibitor exposure. Results: A total of 16 individual studies evaluating a total of 198 404 patients were included for analysis. Studies ranged from 52 weeks through 5 years. In the primary random-effects analysis, DPP-4 inhibitor exposure resulted in a nonsignificant increase in the risk of IBD (RR = 1.52; 95% CI = 0.72 to 3.24; I2 = 54.2%). Sensitivity analysis using a fixed-effects model demonstrated significantly increased risk (RR = 3.01; 95% CI = 2.30-3.93). DPP-4 inhibitor use significantly increased the risk of CD (RR = 2.47; 95% CI = 1.36 to 4.48). All findings were driven by the inclusion of 1 large study. Conclusion and Relevance: Based on a conservative random-effects analysis, DPP-4 inhibitors do not appear to increase the risk of developing inflammatory bowel disease. However, long-term postmarketing surveillance is warranted.

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