Diabetes risk reduced with TNF inhibitors, hydroxychloroquine

Solomon DH. JAMA. 2011;305:2525-2531.

Tumor necrosis factor inhibitors and hydroxychloroquine were found to be protective against the development of diabetes in patients with rheumatoid arthritis or psoriasis, according to data from a retrospective cohort study.

Coupled with recent data on the effects of tumor necrosis factor (TNF) inhibitors and hydroxychloroquine on improved insulin and glucose metabolism and reduced diabetes risk, disease-modifying antirheumatic drugs (DMARDs) and immunosuppression may have a role in the prevention of diabetes, researchers wrote.

The study, conducted by researchers at Brigham and Women’s Hospital in Boston, included data on 13,905 patients with rheumatoid arthritis or psoriasis diagnosed on at least two hospital visits. The analysis was conducted using administrative data from two large health insurance programs in Canada and the United States. Patients had 22,493 treatment episodes and began one of four DMARDs between January 1996 and June 2008: TNF inhibitors with or without other DMARDs; methotrexate without TNF inhibitors or hydroxychloroquine; hydroxychloroquine without TNF inhibitors or methotrexate; or other nonbiologic DMARDs without TNF inhibitors, methotrexate or hydroxychloroquine. The mean follow-up was 5.8 months.

The researchers reported 267 newly diagnosed cases of diabetes: 55 in nonbiologic DMARD users; 80 in TNF inhibitor users; 82 in methotrexate users; and 50 in hydroxychloroquine users. Patients who switched to other nonbiologic DMARDs had the highest incidence rate of diabetes (50.2; 95% CI, 47.3-53.2), and those who used TNF inhibitors had the lowest incidence rate (19.7; 95% CI, 19.1-20.3).

Compared with other nonbiologic DMARDs, TNF inhibitors and hydroxychloroquine were associated with a reduced RR for diabetes. The adjusted HRs for diabetes were: 0.62 (95% CI, 0.42-0.91) for TNF inhibitors; 0.77 (95% CI, 0.53-1.13) for methotrexate and 0.54 (95% CI, 0.36-0.80) for hydroxychloroquine compared with other nonbiologic DMARDs, according to the researchers.

“The findings from this epidemiologic study should be considered hypothesis-generating,” they wrote. “However, considering these results in light of prior findings regarding improved insulin and glucose metabolism and reduced [diabetes] risk with hydroxychloroquine and TNF inhibitors, there is evidence suggesting a possible role for DMARDs and immunosuppression in [diabetes mellitus] prevention.”

The researchers said consideration should be given to a randomized controlled trial to determine whether these agents can prevent diabetes in patients with systemic inflammatory disorders.

Disclosure: Dr. Solomon reports receiving support through a research grant from Abbott, directing an educational course supported by Bristol-Myers Squibb and serving in an unpaid role on two Pfizer-sponsored trials.

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