Efficacy and safety of hydroxychloroquine for managing glycemia in type-2 diabetes: A systematic review and meta-analysis.

Aims: No Cochrane meta-analysis with grading of evidence is available on use of hydroxychloroquine (HCQ) in type-2 diabetes (T2DM). This meta-analysis evaluated the efficacy and safety of HCQ in T2DM. Methods: Electronic databases were searched using a Boolean search strategy: ((hydroxychloroquine) OR (chloroquine*)) AND ((diabetes) OR ("diabetes mellitus") OR (glycemia) OR (glucose) OR (insulin)) for studies evaluating hydroxychloroquine for glycemic control in T2DM. The primary outcome was a change in glycated haemoglobin (HbA1c). The secondary outcomes were changes in other glycemic/lipid parameters and adverse effects. Results: Data from 11 randomized controlled trials (RCTs) (3 having placebo as controls [passive controls] and 8 having anti-diabetes medications as controls [active controls]) involving 2,723 patients having a median follow-up of 24 weeks were analyzed. About 54.54% of the RCTs were of poor quality as evaluated by the Jadad scale. The performance bias and detection bias were at high risk in 63.64% of the RCTs. The HbA1c reduction with HCQ was marginally better compared to the active (mean differences [MD]-0.17% [95%, CI:-0.30--0.04;P=0.009;I2=89%; very low certainty of evidence, VLCE]), and passive (MD-1.35% [95%CI:-2.10--0.59;P=0.005;I2=74%]) controls. A reduction in fasting glucose (MD-16.63mg/dL[95%, CI: -25.99 - -7.28mg/dL;P<0.001;I2=97%;VLCE]) and post-prandial glucose [MD -8.41mg/dL (95%CI: -14.71 - -2.12mg/dL;P=0.009;I2=87%;VLCE]), appeared better with HCQ compared to active controls. The total adverse events (risk ratio [RR]0.93 [95% CI:0.68-1.28]; P=0.65;I2=66%) were not different with HCQ compared to the controls. Conclusion: The routine use of HCQ in T2DM cannot be recommended based on the current evidence.