Effect of Hydroxychloroquine on Insulin Sensitivity and Lipid Parameters in Rheumatoid Arthritis Patients Without Diabetes Mellitus: A Randomized, Blinded Crossover Trial

Authors

  • Daniel H. Solomon,

    Corresponding author
    1. Brigham and Women's Hospital, Boston, Massachusetts
    • Division of Rheumatology, Division of Pharmacoepidemiology, Brigham and Women's Hospital, 75 Francis Street, PBB-B3, Boston, MA 02115. E-mail: dsolomon@partners.org

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    • Dr. Solomon has received salary support from research grants (more than $10,000 each) to Brigham and Women's Hospital from Amgen, Lilly, Pfizer, and the Consortium of Rheumatology Researchers of North America, has served in unpaid roles on studies sponsored by Pfizer, Novartis, Lilly, and Bristol Myers Squibb, and has received royalties from UpToDate.

  • Rajesh Garg,

    1. Brigham and Women's Hospital, Boston, Massachusetts
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  • Bing Lu,

    1. Brigham and Women's Hospital, Boston, Massachusetts
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  • Derrick J. Todd,

    1. Brigham and Women's Hospital, Boston, Massachusetts
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  • Emileigh Mercer,

    1. Brigham and Women's Hospital, Boston, Massachusetts
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  • Tabatha Norton,

    1. Brigham and Women's Hospital, Boston, Massachusetts
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  • Elena Massarotti

    1. Brigham and Women's Hospital, Boston, Massachusetts
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    • Dr. Massarotti has received consultant fees, speaking fees, and/or honoraria (less than $10,000 each) from Human Genome Sciences, Questcore, Amplimmune, and Alexion, has provided expert testimony for National Medical Consulting, has received research support from Human Genome Sciences, Bristol Myers Squibb, and Sanofi, and receives royalties from UpToDate.


Abstract

Objective

Observational studies suggest that hydroxychloroquine (HCQ) may reduce the risk of developing diabetes mellitus in patients with rheumatoid arthritis (RA). We examined the effect of HCQ on insulin resistance in subjects without diabetes mellitus with stable RA.

Methods

Twenty-three RA subjects not currently using HCQ completed a 16-week, double-blind crossover study. Subjects were randomly allocated to receive HCQ (6.5 mg/kg/day) or placebo for the first 8 weeks, followed by crossover to the other arm for the final 8 weeks. Subjects underwent oral glucose tolerance testing and fasting lipid measurements at baseline, 8 weeks, and 16 weeks. The change ± SD from baseline in insulin sensitivity index (ISI), homeostatic model assessment for insulin resistance (HOMA-IR), and lipid parameters were compared between placebo and HCQ using linear regression.

Results

The mean patient age was 56 years, with 96% women, and the median body mass index was 26.0 kg/m2. After 8 weeks of HCQ, the mean ± SD ISI increase was 0.4 ± 2.9 compared with a small increase during placebo of 0.14 ± 3.1 (adjusted P = 0.785), and the mean ± SD HOMA-IR decrease was 0.3 ± 1.5 during HCQ versus a decrease of 0.42 ± 1.4 during placebo (adjusted P = 0.308). Small decreases in total cholesterol (12.7 mg/dl) and low-density lipoprotein (LDL) cholesterol (12.4 mg/dl) were observed during the HCQ treatment periods (both adjusted P < 0.05 compared to placebo).

Conclusion

HCQ use for 8 weeks in patients without diabetes mellitus with stable RA produced no significant change in insulin resistance. We observed small and statistically significant improvements in total and LDL cholesterol during HCQ treatment.

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