Impact of decreased insulin resistance by ezetimibe on postprandial lipid profiles and endothelial functions in obese, non-diabetic-metabolic syndrome patients with coronary artery disease

The association between insulin resistance and lipid dysmetabolism after consuming a meal is unclear. We aimed at assessing the effects of ezetimibe on postprandial hyperlipidemia and hyperinsulinemia and to find out whether the medication improves endothelial function in obese metabolic syndrome (MetS) patients with coronary artery disease (CAD). We obtained oral fat loading test results (4 and 6 h after load) and brachial flow-mediated vasodilation (FMD) measurements before and 24 weeks after ezetimibe treatment initiation from 27 MetS patients with CAD and from 68 control patients with CAD alone. Serum triglyceride (TG) and insulin levels (2 h after the loading dose) were significantly higher in MetS patients than in control patients. The incremental areas under the curve (iAUCs) for these levels decreased significantly after ezetimibe treatment in MetS patients but not in control patients. Treatment with ezetimibe resulted in significant FMD changes in MetS patients (from 3.4 to 4.9%, P = 0.002), but not in control patients (from 5.1 to 5.4%, P = 0.216). When MetS patients were divided into two groups based on the median insulin iAUC reduction rate (higher group ≥ 34%, n = 14; lower group < 34%, n = 13), those in the higher group showed a significantly higher rate of change in the iAUCs of TG and FMD than those in the lower group (TG, 31.0% vs. 10.8%; P = 0.033; FMD, 39.2% vs. 9.8%; P = 0.037). These results suggest that ezetimibe may reverse insulin resistance, reducing lipid dysmetabolism after a meal and endothelial dysfunction in MetS patients with CAD.