The effectiveness of hydroxychloroquine in patients with type 2 diabetes mellitus who are refractory to sulfonylureas—a randomized trial
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AIM: To assess the glucose-lowering efficacy, responsiveness, duration of action and impact on quality-of-life of hydroxychloroquine (HXCHL), when added as an antihyperglycemic agent to patients with sulfonylurea-refractory type 2 diabetes. METHODS: One hundred and thirty-five obese patients with type 2 diabetes (mean age 57.5 years) and a glycated hemoglobin (GHb) > or = 11% despite maximum sulfonylureas were randomly allocated to the addition of HXCHL (up to 300 mg bid) or placebo and followed for up to 18 months. Randomization was stratified by baseline GHb (<13.5% versus > or = 13.5%). The primary outcome was 'blinded' withdrawal of study drug due to unacceptable glycemic control; GHb, glucose tolerance, lipids, and quality of life were also assessed. RESULTS: Those on placebo were more likely to be withdrawn from study drug because of unacceptable glycemic control than patients randomized to HXCHL (95.5 and 69.6% given placebo and HXCHL, respectively; P=0.0001). During the first 6 months, HXCHL decreased GHb by an absolute amount of 1.02% more than placebo (95% CI 0.24, 1.81). Glucose tolerance and LDL cholesterol improved during the first 3 months of therapy. No significant adverse effects were noted. Factors that predicted responsiveness included an initial GHb <13.5%, early responsiveness to study drug, and no prior metformin use. Lower GHb levels at baseline predicted a better response; the hazard of withdrawal increased 36% (95% CI 11%, 66%) for every 1% increase in GHb even in patients whose baseline GHb was <13.5%. CONCLUSIONS: HXCHL improves glycemic control in sulfonylurea-refractory patients with poorly controlled type 2 diabetes.