Incretin-based drugs and intestinal obstruction: A pharmacovigilance study.

Summary Aims To investigate the risk of intestinal obstruction associated with incretin-based drugs by performing a disproportionality analysis of adverse reaction reports in a global pharmacovigilance database. Methods We conducted a case/non-case analysis using VigiBase, the World Health Organization's adverse drug reactions (ADR) database, to assess intestinal obstruction reporting associated with incretin-based drugs (glucagon-like peptide 1 analogues [GLP-1a] and dipeptidyl peptidase 4 inhibitors [DPP-4i]. Cases were defined as reports of gastrointestinal stenosis and obstruction (MedDRA High Level Group Term) and non-cases were all other reactions recorded. Disproportionality analysis were performed by computing reporting odds ratios (ROR) with their 95% confidence interval (95%CI) within all ADR reports concerning diabetes drugs from January 2007 to January 2018 and in a restricted sample including only serious reports. Results A total of 501,244 ADR with diabetes drugs were reported in VigiBase during the study period. We identified 452 intestinal obstructions involving an incretin-based drug. In disproportionality analyses, intestinal obstructions were more than 4.5 times more frequently reported with incretin-based drugs than with other diabetes drugs (ROR 4.52, 95% CI: 3.87–5.28) with a higher signal for serious cases and for DPP-4i (ROR 8.66, 95% CI: 7.27–10.32) compared to GLP-1a (ROR 3.05, 95% CI: 2.54–3.66). Conclusions We identified a pharmacovigilance signal that suggests a risk of potentially serious intestinal obstruction associated with incretin-based drugs, as a class and with a greater signal for DPP4-i. Other studies are needed to confirm and better understand the potential risk of intestinal obstruction associated with incretin-based drugs.