Ezetimibe and diabetes mellitus:a new strategy for lowering cholesterol

Diabetes mellitus is a well-recognized risk factor for cardiovascular diseases, so an “aggressive” therapeutic approach is necessary for some high-risk patients. Low-density lipoprotein (LDL) cholesterol is the leading modifiable risk factor for the development of atherosclerotic cardiovascular diseases (ACVD). It is known that statins are the gold standard to control LDL cholesterol and reduce the risks associated with ACVD; however, many patients do not achieve their LDL cholesterol target or are unable to use this class of drugs due to associated side effects. Recent stu­dies of non-statin cholesterol-lowering drugs (ezetimibe, proprotein convertase subtilisin/kexin type 9 inhibitors) have demonstrated benefits in the treatment of ACVD, and new drugs (bempedoic acid, inclisiran) have shown promising results in preclinical and clinical studies. New evidence suggests that prescription of ezetimibe as an addition to statins provides an additional cardioprotective effect. This review aims to discuss the role of ezetimibe in the treatment of patients with diabetes mellitus and dyslipoproteinemia and to consider its efficacy and safety. The combined use of low- or moderate-intensity therapy with statins and ezetimibe involves two complementary mechanisms: a decrease in the intracellular concentration of cholesterol with increased uptake of LDL cholesterol by hepatocytes and a decrease in cholesterol absorption in the intestines. These mechanisms act synergistically and can provide the same overall effect as when using high-intensity statin therapy. The safety of combined therapy is equivalent to that of monotherapy with HMG-CoA reductase inhibitors in similar doses. This combination is generally better tolerated than high doses of HMG-CoA reductase inhibitors and has advantages in patients at risk of myo­pathy and statin-induced type 2 diabetes. Thus, despite some ca­veats, ezetimibe remains the drug of choice in the arsenal of pharmacological agents.