PITTSBURGH, Pennsylvania—The old, inexpensive, antimalarial drug hydroxychloroquine (HCQ) is less impressive than some of the newer biologicals for treating rheumatoid arthritis (RA) but may have a new role in protecting RA patients against diabetes. According to a report in today's Journal of the American Medical Association the risk of new-onset diabetes dropped by 77% in RA patients who had taken HCQ for more than 4 years.1
RA patients are considered to be at increased for diabetes because they tend to be less active and to take corticosteroids that can cause weight gain.
Results of 20-year ARAMIS study
The analysis is based on data from the ARAMIS (Arthritis, Rheumatism, and Aging Medical Information System) longitudinal, multicenter, observational study begun in 1976 and sponsored by the Arthritis Foundation of Western Pennsylvania, the National Arthritis Foundation, the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the Intramural Research Program at NIAMS, and the National Institutes of Health.
Researchers studied 4905 adults with RA, of whom 1808 had taken HCQ and 3097 had not taken the drug. None of the patients had diabetes at baseline, and the follow-up period was 21.5 years. During this time, diabetes developed in 54 patients who had taken HCQ and in 171 patients who had not. Incidence rates per 1000 patient-years of observation were 5.2 with HCQ and 8.9 without HCQ (P <.001).
The hazard ratio for incident diabetes was .62 for patients who had taken HCQ compared with those who had not, and the risk of diabetes decreased with longer duration of HCQ, from .83 with 1 year or less of use to .23 with more than 4 years of use. Patients were taking an average 340 mg/day of HCQ, with 64% of patients taking HCQ 400 mg/day.
"[The] reduction in diabetes risk persisted after adjusting for diabetes risk factors and other covariates such as BMI, functional status, and corticosteroid use, " Dr. Wasko writes. Dr. Wasko also found that the RA patients who developed diabetes were less likely to need hypoglycemic agents if they had taken HCQ.
HCQ a tool for widespread diabetes prevention?
The effects of HCQ compared favorably with those of a number of other drugs that have been studied in clinical trials for diabetes prevention, including rosiglitazone (AvandiaTM), hormones, metformin, acarbose, and ramipril. HCQ also has a notably long safety record and was not associated with any negative interactions with other RA drugs in this study. Preclinical studies have shown that antimalarials improve insulin secretion and peripheral insulin sensitivity, and this is likely to be the mechanism behind the diabetes preventive effect seen in RA patients, according to Dr. Wasko.
"[I]t 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," Dr. Wasko said.
"HCQ already has a role in long-term treatment for RA, potentially moderating lipids and having a weak anticlotting effect. 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 the 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," Dr. Wasko concluded.
Table: Hydroxychloroquine Use and Diabetes Risk in RA