Dipeptidyl peptidase-4 inhibitors lower the risk of autoimmune disease in patients with type 2 diabetes mellitus: A nationwide population-based cohort study

Aims: To evaluate the real-world effect of dipeptidyl peptidase-4 inhibitor (DPP4i) on the incidence of autoimmune diseases (AD), including rheumatoid arthritis (RA), inflammatory bowel diseases, multiple sclerosis and systemic lupus erythematosus. Methods: We identified new users of DPP4i (n = 497 619) or non-DPP4i (n = 643 165) oral combination therapy between 1 January 2011 and 30 June 2015 among patients with type 2 diabetes mellitus in the Korean national health insurance claims database. Patients were followed from the date of initiation of combination therapy until AD outcome, censoring for treatment discontinuation or switching, death or end of study (31 August 2016). Adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for RA, inflammatory bowel diseases, other AD (multiple sclerosis and systemic lupus erythematosus), and the composite of all outcomes were estimated using propensity score (PS)-adjusted Cox model. Results: In the PS-weighted and PS-matched analysis, the risk of incident RA was decreased for DPP4i initiators compared with non-DPP4i initiators (aHR 0.67 [95% CI 0.49–0.92] and aHR 0.72 [95% CI 0.51–1.01], respectively). In both analyses, the risk of incident composite AD was also decreased for DPP4i initiators compared with non-DPP4i initiators (aHR 0.82 [95% CI 0.68–0.99] and aHR 0.76 [95% CI 0.62–0.93], respectively). Conclusions: In this large population-based cohort study, upfront DPP4i combination therapy was associated with a lower risk of composite AD compared with initial non-DPP4i combination therapy.