DPP-4 Inhibitor-Induced Rheumatoid Arthritis Among Diabetics: A Nested Case–Control Study

INTRODUCTION: The risk of rheumatoid arthritis (RA) associated with dipeptidyl peptidase-4 inhibitor (DPP-4i) use is unclear. This study assesses the RA risk associated with DPP-4i use among a diabetic cohort initiating second-line therapy. METHODS: This was a nested case–control study, using the adult diabetic population starting second-line antidiabetic therapy from IMS LifeLink Plus(®) database (2006–2015). Cases were those with two or more RA diagnosis, at least one prescription, and 180 days enrollment prior to the event date (earliest of the two: first RA diagnosis, first RA prescription). Controls were drawn from the nest after matching (1:15) with cases on index date (± 90 days), age (± 5 years), sex, and event date (imputed to have the same time difference between cohort entry and event date as the matched case). Exposure and covariate information was gathered from the 180-day period prior to event date. Conditional logistic regression was used to assess exposure among cases and controls. Adjusted analysis was carried out after controlling for important medications and comorbidities. RESULTS: The final sample consists of 790 cases and 11,850 controls; of these, 151 cases (19.11%) and 2177 controls (18.37%) had DPP-4i claims during the exposure assessment period. DPP-4i therapy was not significantly associated with the development of RA after adjusting for covariates (OR = 1.156, 95% CI 0.936–1.429). Changing the exposure definition or exposure window to 1 year and subgroup analyses yielded similar results except for the non-insulin-using subgroup (OR = 1.299, 95% CI 1.001–1.985) which showed a significant positive association. CONCLUSION: DPP-4i were not significantly associated with the risk of RA compared with other second-line antidiabetic therapies.