Effect of ezetimibe on glycemic control: a systematic review and meta-analysis of randomized controlled trials

Given the increased risk of incident diabetes and the side effects on glycemic control with statin treatment, statin and ezetimibe combination therapy has been widely used. However, whether the same concern exists in ezetimibe remains uncertain. This meta-analysis aimed to investigate the influence of ezetimibe treatment on glycemic control. Articles were searched from PubMed, EMBASE, and Cochrane Library. Randomized controlled trials (RCTs) were included if they compared the effects of ezetimibe with placebo, ezetimibe plus statin with the same statin, or low-dose stain plus ezetimibe with high-dose statin on FBG and glycosylated hemoglobin A1c (HbA1c). Of the 2440 articles retrieved, 16 RCTs were included. Ezetimibe did not cause side effects on FBG (WMD -0.62, 95% CI: -3.13 to 1.90) and HbA1c (WMD 0.07, 95% CI: -0.07 to 0.20%). No significant changes in FBG (WMD -1.78, 95% CI: -6.33 to 2.77%) and HbA1c (WMD -0.05, 95% CI: -0.14 to 0.05%) were observed in ezetimibe plus low-dose statin treatment compared with high-dose statin. According to subgroup analysis, in comparison with high-dose statin, ezetimibe plus low-dose statin taken for more than 3 months showed a significant decrease in FBG (WMD -7.12, 95% CI: -13.86 to -0.38%) compared with that taken for less than 3 months (WMD 0.90, 95% CI: -2.91 to 4.71%). Nevertheless, this difference was invalid when the study conducted by Dagli et al. was removed. Compared with high-dose statin therapy, ezetimibe with low-dose statin for more than 3 months may have a beneficial tendency of effects on glycemic control.