Patients who take hydroxychloroquine for their rheumatoid arthritis symptoms also show a dose-dependent reduction in their risk for developing diabetes, results of a large study suggest.
Diabetes risk decreased by as much as 77% in patients who took the antimalarial drug hydroxychloroquine for more than 4 years, “a finding that is comparable or superior to that of other drugs studied in clinical trials: rosiglitazone, combination hormone therapy, estrogen [only], metformin, acarbose, and ramipril,” the study researchers reported.
This is the first evidence that has ever been reported suggesting that hydroxychloroquine reduces the risk of diabetes in RA patients, wrote Dr. Mary Chester M. Wasko, of the University of Pittsburgh, and her associates.
Antimalarials are known to cause hypoglycemia and are thought to improve insulin secretion and peripheral insulin sensitivity. They “have been explored as an adjunct to insulin and oral hypoglycemic agents for poorly controlled type 2 diabetes,” Dr. Wasko and her associates said.
The investigators studied the possible link between use of hydroxychloroquine and diabetes risk in an established RA cohort with more than 20 years of follow-up.
The 4,905 subjects in this longitudinal observational study were treated at seven RA practice sites across North America from 1976 through 2004. A total of 1,808 reported use of hydroxychloroquine at some time during the study, most of them for an average of 3 years.
Diabetes developed in 70% of the subjects who had never taken the antimalarial drug, compared with only 48% of those who had ever taken it.
Diabetes incidence rates were 8.9 per 1,000 patient-years of observation among those who had never before taken hydroxychloroquine, compared with 5.2 per 1,000 patient-years for those who had taken the drug.
In addition, “the relative risk of developing diabetes progressively declined with increasing time taking hydroxychloroquine,” the investigators said (JAMA 2007;298:187–93).
Patients who did develop diabetes after taking the antimalarial were less likely than were those who hadn't taken it to need oral hypoglycemic medication.
“Hydroxychloroquine use may modify the clinical manifestations of hyperglycemia, or it may attenuate hyperglycemia and reduce the need for medications once this diagnosis is established,” Dr. Wasko and her associates commented.
Although antimalarials do not address RA signs and symptoms as well as other current treatment options, their toxicity profile is better, so they are used for mild to moderate disease and in combination therapy.
Unlike the traditional RA medications, antimalarials are well tolerated, do not require routine laboratory monitoring for toxicity, confer no increased risk of infection or malignancy, and carry “minimal” risk for adversely affecting internal organs when dosing is tailored to body weight, the researchers said.
Even though this study involved only RA patients, the results also may apply to people who do not have RA, because hydroxychloroquine may prove beneficial in preventing diabetes in high-risk members of the general population, the researchers added.