Cholesterol Absorption Inhibitors (Ezetimibe) and Bile Acid Binding Resins (Colesevelam HCl) as Therapy for Dyslipidemia in Patients with Diabetes Mellitus

Ezetimibe blocks the intestinal absorption of both biliary and dietary cholesterol by inhibiting intestinal sterol transporters. Therapeutically, ezetimibe alone and in combination with statins is primarily indicated to lower low-density lipoprotein (LDL) cholesterol levels. Additionally, ezetimibe lowers non-high-density lipoprotein (non-HDL) cholesterol, apolipoprotein B, triglycerides, and remnant-like particle cholesterol and modestly raises HDL cholesterol levels. When combined with statins, ezetimibe may also lower C-reactive protein levels. These lipid effects have particular application when treating the dyslipidemia often found in patients with type 2 diabetes mellitus (T2DM). Colesevelam HCl is another gastrointestinal-acting lipid-altering drug, which is classified as a bile acid sequestrant (BAS). Earlier, BAS were among the first drugs approved to lower cholesterol levels, and clinical outcomes trials supported their use in not only lowering cholesterol but also improving atherosclerotic coronary heart disease (CHD) outcomes. Unfortunately, the first marketed BAS (e.g., cholestyramine and colestipol) were poorly tolerated and had substantial potential for drug interactions which substantially limited their clinical use. Colesevelam HCl was approved in the year 2000 as a new generation of BAS that was specifically designed to be better tolerated, with less potential for drug interactions. Additionally, BAS were known for decades to not only reduce cholesterol levels but also reduce glucose levels. In 2008, colesevelam HCl received regulatory approval as an anti-diabetes mellitus agent, which was in addition to its established indication as a cholesterol-lowering agent. This chapter focuses on the use of ezetimibe and colesevelam HCl in the management of dyslipidemia in patients with T2DM.