Risk of New-Onset Diabetes Mellitus Associated with Antirheumatic Drugs in Patients with Rheumatoid Arthritis: A Nationwide Population Study

Background: This study aimed to investigate the effect of disease-modifying antirheumatic drugs (DMARDs) on diabetes mellitus (DM) development in rheumatoid arthritis (RA). Methods: This nested case–control study with a cohort of 69,779 DM-naïve adult patients with RA was conducted from 2011 to 2019 in South Korea. Cases with incident DM were identified and individually matched to randomly selected controls (1:4). DMARDs use was measured for 1 year before the index date and stratified by exposure duration. The association of each DMARD use with DM risk was estimated using conditional logistic regression adjusted for comorbidities and concomitant drug use. Results: Of the patients, 5.4% were newly diagnosed with DM. The use of statins and a higher cumulative dose of corticosteroids were associated with an increased DM risk. In a multivariable-adjusted analysis, cumulative duration of exposure (CDE) >270 days/year, hydroxychloroquine (HCQ; adjusted odds ratio [aOR], 0.76) and methotrexate (MTX; aOR, 0.81) were associated with a significant decrease in DM risk, and tacrolimus (TAC; aOR, 1.27) was associated with an increased risk. Conclusions: Long-term use of HCQ and MTX (>270 days/year) was associated with a reduction in DM incidence as opposed to TAC.