Science & Technology/Teaching an Old Drug New Tricks

Common rheumatoid arthritis treatment shows potential for diabetes prevention, Pitt-led study shows

Far fewer rheumatoid arthritis patients treated with the drug hydroxychloroquine (HCQ) went on to develop diabetes compared with those who never took the drug, according to a 20-plus-year Pitt School of Medicine-led study reported in the Journal of the American Medical Association July 10.

In addition, those using HCQ who did develop diabetes were less likely to take medications to manage their disease after diagnosis.

The multicenter observational study of 4,905 adults with rheumatoid arthritis (RA) found that relative risk progressively declined by as much as 77 percent after four years of treatment with HCQ, a common antimalarial medication that also is used for rheumatoid arthritis and other autoimmune disorders.

“This reduction in risk persisted even after adjusting for other diabetes risk factors among these patients, such as body-mass index, degree of disability, and use of corticosteroids,” said Mary Chester M. Wasko, a rheumatologist who is a professor in Pitt’s medical school.

Because people with RA tend to be less active and take corticosteroids that can cause weight gain, they are often considered to be at higher risk for developing diabetes, a disease in which blood sugar levels become abnormally high because of the body’s inability to use or produce the hormone insulin.

“Another interesting finding was that the rheumatoid arthritis patients who developed diabetes were less likely to need blood sugar-lowering medication to manage their disease,” said Wasko, whose clinical research has focused on long-term health improvement in patients with RA. “However, it is most exciting to consider that this drug might be appropriate for people with prediabetes as a preventive therapy—much in the same way as a daily baby aspirin is suggested for people at high risk for heart disease.”

Nationally, diabetes is the fifth-leading cause of death, according to the American Diabetes Association. Many people first become aware of the disease when confronted with one of its life-threatening complications, which include heart disease, blindness, high blood pressure, stroke, kidney disease, and circulatory problems that can lead to amputation.

Results show that HCQ’s association with reduction in diabetes risk is comparable or superior to that of a number of other drugs studied in clinical trials for diabetes prevention and treatment, including rosiglitazone, hormones, metformin, acarbose, and ramipril. And recent questions have arisen concerning rosiglitazone, marketed as Avandia, and a reported increased risk of heart attack.

Although HCQ can cause such side effects as nausea, headache, and dizziness, the drug has a long history of being generally safe and well-tolerated.

In addition, Wasko and her colleagues observed no apparent negative interactions between HCQ and other drugs commonly used by RA patients, such as methotrexate and prednisone. An important limitation of the study, however, is that investigators used self-report information from patients collected in follow-up twice yearly that did not include confirmation by laboratory tests.

Other studies of the blood sugar-lowering effects of HCQ have shown minimal use for the drug as a treatment for people with established diabetes, Wasko said, stressing that the treatment’s real promise may be in prevention.

“HCQ already has a role in long-term treatment for RA, potentially moderating lipids and having a weak anticlotting effect,” she said. “But, optimistically speaking, endocrinologists can identify people who are at high risk for diabetes due to obesity, family history, lipid profile, or other characteristics. HCQ may also have a role in delaying onset of diabetes. More research is needed to verify our findings in people with RA, and also to determine how this medicine works. But my ultimate hope is that this relatively inexpensive, safe drug will be studied as a way to reduce diabetes risk for people who do not have RA.”

In addition to Pitt, institutions participating in the study are Stanford University, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the University of Cincinnati.