Hydroxychloroquine for Rheumatoid Arthritis Reduces Risk for Diabetes

July 10, 2007 — Hydroxychloroquine reduces the risk of developing diabetes mellitus, according to a prospective, multicenter observational study involving 4905 patients who were enrolled to collect data about the course of rheumatoid arthritis. This analysis, reported in the July 11 issue of the Journal of the American Medical Association, also found that the longer the patients took hydroxychloroquine, the lower their risk of diabetes.
The study began in 1976, when researchers enrolled patients diagnosed with rheumatoid arthritis who were aged 16 years or older into a longitudinal, observational study involving 7 outpatient rheumatology practices in North America. Follow-up continued at 6-month intervals into 2006 (for 21.5 years).
Of the 4905 patients included in this analysis, 1808 (37%) reported hydroxychloroquine use at some time during the observation period. Also during this time, researchers recorded incident diabetes in 54 patients who had taken hydroxychloroquine at some point vs 171 patients who had never taken the drug. This is an incidence rate of 5.2 per 1000 patient-years vs 8.9 per 1000 patient-years of observation, respectively (P < .001).
Overall, the hazard ratio for incident diabetes among patients who had taken hydroxychloroquine was 0.62% compared with those who had never taken it (95% confidence interval, 0.42 – 0.92). Poisson regression analysis revealed that the risk of incident diabetes was significantly reduced when the duration of hydroxychloroquine use was increased (P < .001). Among the 384 patients who took hydroxychloroquine for more than 4 years, the adjusted, relative risk of developing diabetes was 0.23 (95% confidence interval, 0.11 – 0.50; P < .001) compared with patients who had never taken the drug.
Although hydroxychloroquine is often used to treat malaria, it is also a "long-standing safe and inexpensive treatment for autoimmune diseases such as rheumatoid arthritis and system lupus erythematosus," write Mary Chester M. Wasko, MD, MSc, Division of Rheumatology and Clinical Immunology, University of Pittsburgh, Pennsylvania, and colleagues. They note that in vitro and animal studies suggest that antimalarials improve insulin secretion and peripheral insulin sensitivity, and that in humans, hypoglycemia is a rare but known adverse effect of treatment.
The authors also write that their findings may occur in patients without rheumatoid arthritis because the beneficial changes in glucose metabolism and insulin sensitivity appear independent of a diagnosis of rheumatoid arthritis.
The authors conclude: "Further prospective studies are needed to determine whether this treatment option should be considered a standard component of rheumatoid arthritis combination therapy in the future, and to evaluate the potential role of hydroxychloroquine as a preventative agent for diabetes among high-risk individuals in the general population."
This study was funded by the Arthritis Foundation of Western Pennsylvania, the National Arthritis Foundation, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and an Intramural Research Program of the National Institutes of Health. Dr. Wasko has been a consultant to Centocor and has served as a coinvestigator for Merck. She has also received reimbursement as an investigator for Centocor, Aventis (ending in 2002), Roche, Human Genome Sciences, and Novartis. No other authors reported any relevant financial relationships.
JAMA. 2007;298(2):187–193.