Hydroxychloroquine and Risk of Diabetes

Hydroxychloroquine is a safe and inexpensive treatment for rheumatoid arthritis (RA) and systemic lupus erythematosus. This antimalarial drug also may have an effect on glucose metabolism and could prevent or delay the onset of diabetes mellitus. This hypothesis is based on the observations that a) low blood sugar is a recognized side effect of antimalarial treatment, and b) hydroxychloroquine has been used with good results in combination with traditional drugs for regulating glucose levels in people with type 2 diabetes.

What Problem Was Studied?

Physicians and scientists from several centers around the country undertook a study to determine whether hydroxychloroquine use among people with RA might have a protective effect on the development of diabetes.

What Was Done in the Study?

Arthritis Foundation-funded researchers Mary Chester M. Wasko, MD, MSc and Jennifer R. Elliott, MD, both of the University of Pittsburgh in Pennsylvania, along with their co-investigators, used data from the Arthritis, Rheumatism, and Aging Medical Information System (ARAMIS). For the purposes of this study, the earliest study entry date used was January 1983. Follow-up assessment continued every six months until diabetes onset, death, study withdrawal, or study end date (July 2004). Information on hydroxychloroquine use, length of use and the onset of diabetes was gathered and analyzed.

What Were the Study Results?

Of the 4,905 participants included in the study, 1,808 (37 percent) took hydroxychloroquine at some point during their treatment, and more than half of those were taking the antimalarial at study entry. On average, participants who had ever taken hydroxychloroquine took the drug 55 percent of the total observation time.

All told, 225 of the 4,905 participants developed diabetes during the study – 54 who had taken the drug at some point in time and 171 who had never taken it. These figures give significantly different incidence rates for diabetes depending on whether the patient took hydroxychloroquine or not. Furthermore, the risk of developing diabetes progressively declined with increasing time taking the medication.

To be certain that risk factors for diabetes – such as age, sex, body mass index, functional ability, and corticosteroid use – did not influence the results, the research team ran statistical analyses to control for those factors. They found that the use of hydroxychloroquine is associated with a reduced risk of developing diabetes in people with RA, even after adjusting for known risk factors.

As with any study, the design was not perfect. In this particular study, all information used for the analyses was provided by the study participants, and the results were not verified by lab testing or medical record review. However, given the scientific evidence supporting the hypothesis and the statistical strength of the results, Dr. Wasko says, “these findings have potentially far-reaching significance, as this drug may have a role in preventing type 2 diabetes in the general population.”

What Does This Mean for People with Arthritis?

The authors conclude that their study shows a significant, dose-related association between hydroxychloroquine therapy and reduced risk of diabetes in adults with RA. They go on to state, “As quality of life and life expectancy improve for patients with rheumatoid arthritis, and health care costs escalate, the use of inexpensive, safe therapies that have multiple beneficial effects is attractive. Further prospective studies are needed to determine whether this treatment option should be considered a standard component of RA combination therapy in the future.”

Wasko MCM, Hubert HB, Lingala VB, et al. Hydroxychloroquine and risk of diabetes in patients with rheumatoid arthritis. JAMA 2007;298:187-94.

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