Ueda_2023_Clin.Gastroenterol.Hepatol__

BACKGROUND & AIMS: Concerns have been raised that the incretin-based diabetes drugs dipeptidyl peptidase 4 (DPP4) inhibitors and glucagon-like peptide 1 (GLP-1) receptor agonists may increase the risk of intestinal obstruction. We aimed to assess the association between use of DPP4 inhibitors and GLP-1 receptor agonists and the risk of intestinal obstruction. METHODS: Using data from nationwide registers in Sweden, Denmark and Norway, 2013-2021, we conducted two cohort studies, one for DPP4 inhibitors and one for GLP-1 receptor agonists, to investigate the risk of intestinal obstruction as compared with an active comparator drug class (sodium-glucose co-transporter 2 (SGLT2) inhibitors). RESULTS: Among 190321 new users of DPP4 inhibitors (median (IQR) follow-up time, 1.3 (0.6, 2.6) years) and 139315 new users of SGLT2 inhibitors (median (IQR) follow-up time, 0.8 (0.4, 1.7) years), 919 intestinal obstruction events occurred. Use of DPP4 inhibitors, as compared with SGLT2 inhibitors, was not associated with a statistically significant increase in risk of intestinal obstruction (adjusted incidence rate 2.0 vs 1.8 per 1000 person-years; HR, 1.13, 95% CI 0.96 to 1.34). Among 121254 new users of GLP-1 receptor agonists (median (SD) follow-up time, 0.9 (0.4, 1.9) years) and 185027 new users of SGLT2 inhibitors (median (IQR) follow-up time, 0.8 (0.4, 1.8) years), 557 intestinal obstruction events occurred. Use of GLP-1 receptor agonists was not associated with a statistically significant increase in risk of intestinal obstruction (adjusted incidence rate 1.3 vs 1.6 per 1000 person-years; HR, 0.83, 95% CI 0.69 to 1.01). CONCLUSIONS: In this analysis of nationwide data from three Nordic countries, previous safety signals indicating an increased risk of intestinal obstruction with use of DPP4 inhibitors and GLP-1 receptor agonists were not confirmed.