Efficacy and safety of hydroxychloroquine in the treatment of type 2 diabetes mellitus: a double blind, randomized comparison with pioglitazone

Objective: To compare efficacy and safety of hydroxychloroquine with pioglitazone in type 2 diabetes mellitus (T2DM). Research design and methods: This double-blind study randomized 267 uncontrolled type 2 diabetes patients (HbA1c >= 7.5% and <= 11.5%), post 3 months' treatment with glimepiride/gliclazide and metformin, to additionally receive hydroxychloroquine 400 mg/day (n=135) or pioglitazone 15 mg/day (n=132) for 24 weeks. Efficacy was assessed by changes in HbA1c, fasting (FBG) and post-prandial (PPG) blood glucose at Week 12 and Week 24. Results: At Week 12 and Week 24, HbA1c, FBG and PPG significantly reduced from baseline in both groups. Mean reduction in glycemic parameters at Week 12 (HbA1c: -0.56% vs -0.72%, p-0.394; FBG: -0.99 mmol/L vs -1.05 mmol/L, p=0.878; PPG: -1.93 mmol/L vs -1.52 mmol/L, p=0.423) and Week 24 (HbA1c: -0.87% vs -0.90%, p=0.909; FBG: -0.79 mmol/L vs -1.02 mmol/L, p=0.648; PPG: -1.77 mmol/L vs -1.36 mmol/L, p=0.415) was not significantly different between the hydroxychloroquine and pioglitazone groups. Change in total cholesterol (TC) and LDL-C was significant in favor of hydroxychloroquine (TC: -0.37 mmol/L vs 0.03 mmol/L, p=0.002; LDL-C: -0.23 mmol/L vs 0.09 mmol/L, p=0.003). Triglycerides significantly reduced in both groups at Week 24. Mean HDL-C remained unchanged. Study treatments were well tolerated. Conclusion: With favorable effects on glycemic parameters and lipids, hydroxychloroquine may emerge as well tolerated therapeutic option for T2DM. Limitations: The sample size for this study was small. However, based on the encouraging results of this proof-of-concept study, longer duration studies in larger population can be conducted to further confirm these findings.