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Anti-malarial drug may reduce risk of diabetes for patients with rheumatoid arthritis

July 11, 2007

Preliminary research suggests that use of the anti-malarial drug hydroxychloroquine may help reduce the risk of the development of diabetes in patients with rheumatoid arthritis, according to a study in the July 11 issue of JAMA.

Type 2 diabetes mellitus affects nearly 8 percent of US adults, and its prevalence has been increasing. Antimalarials such as hydroxychloroquine, a long-standing safe and inexpensive treatment for an autoimmune disease such as rheumatoid arthritis, theoretically may improve glucose tolerance and prevent diabetes mellitus, according to background information in the article. In vitro and animal studies indicate that antimalarials improve insulin secretion and peripheral insulin sensitivity.

Mary Chester M. Wasko, M.D., M.Sc., of the University of Pittsburgh, Pa., and colleagues examined the association between hydroxychloroquine therapy and risk of diabetes in patients with rheumatoid arthritis. The study included 4,905 adults with rheumatoid arthritis (1,808 had taken hydroxychloroquine and 3,097 had never taken hydroxychloroquine) with no initial diagnosis or treatment for diabetes, with 21.5 years of follow-up (Jan. 1983 through July 2004).

During the observation period, incident diagnoses of diabetes were reported by 54 patients who had taken hydroxychloroquine and by 171 patients who had never taken it. Analysis indicated that patients who had taken hydroxychloroquine had a 38 percent lower risk of developing diabetes, compared with those who had not taken hydroxychloroquine. This risk was further reduced with increased duration of hydroxychloroquine use. Patients who took hydroxychloroquine for more than four years had a 77 percent lower risk of diabetes compared with those who had never taken hydroxychloroquine.

"We report herein the first evidence, to our knowledge, suggesting that use of hydroxychloroquine is associated with a reduced risk of developing diabetes in patients with rheumatoid arthritis," the authors write. "Moreover, risk reduction increased with duration of hydroxychloroquine exposure, supporting a biological action of this drug on glucose metabolism."

"While our study showed a reduction in diabetes incidence specifically in a rheumatoid arthritis cohort taking hydroxychloroquine, these findings also may be expected to occur in patients without rheumatoid arthritis. The beneficial changes in glucose metabolism and insulin sensitivity reported among patients with lupus, patients with type 2 diabetes, and in animal models suggest that these effects are not specific to rheumatoid arthritis."

"Antimalarial drugs may have a role in treating rheumatoid arthritis not only to suppress synovitis [inflammation around the joints] but also to reduce the likelihood of developing glucose intolerance and dyslipidemia [abnormal concentrations of lipids]. 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 rheumatoid arthritis combination therapy in the future, and to evaluate the potential role of hydroxychloroquine as a preventive agent for diabetes among high-risk individuals in the general population," the researchers conclude.

JAMA and Archives Journals