Hydroxychloroquine Use and Decreased Risk of Diabetes in Rheumatoid Arthritis Patients

Background/Objectives: Several studies have associated hydroxy-chloroquine use with decreased risk of diabetes mellitus (diabetes) or improved glycemic control in rheumatoid arthritis patients, but the studies were small or used data from self-report. The present study sought to replicate this protective relationship in a health system using electronic health records with laboratory data and physician diagnoses. Methods: This study is a retrospective cohort of 1127 adults with newly diagnosed rheumatoid arthritis and no diabetes within the Geisinger Health System between January 1, 2003, and March 31, 2008. Patients were classified as ever users (n = 333) or never users (n = 794) of hydroxy-chloroquine. Incident diabetes cases were defined using 2010 American Diabetes Association criteria. Results: The median follow-up times for the ever and never hydroxy-chloroquine users were 26.0 and 23.0 months, respectively (P = 0.28). The median duration of hydroxychloroquine exposure was 14.0 months. Of the 48 cases developing diabetes during observation, 3 were exposed to hydroxychloroquine at time of development and 45 were nonexposed, yielding incidence rates of 6.2 and 22.0 per 1000 per year (P = 0.03), respectively. In time-varying Cox proportional hazards regression models adjusting for sex, age, body mass index, positive rheumatoid factor and anti-cyclic citrullinated peptide antibodies, erythrocyte sedimentation rate, and nonsteroidal anti-inflammatory drug, glucocorticoid, methotrexate, and tumor necrosis factor alpha inhibitor use, the hazard ratio for incident diabetes among hydroxychloroquine users was 0.29 (95% confidence interval, 0.09-0.95; P = 0.04) compared with nonusers. Conclusions: Our findings support the potential benefit of hydroxychloroquine in attenuating the risk of diabetes in rheumatoid arthritis patients. Further work is needed to determine its potential preventive role in other groups at high risk for diabetes.