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

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Lipoproteins in Diabetes Mellitus

Part of the book series: Contemporary Diabetes ((CDI))

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Abstract

Beyond appropriate nutrition, physical activity, and management of other cardiovascular disease (CVD) risk factors, preventive cardiology often involves reducing low-density lipoprotein cholesterol (LDL-C) levels via lipid-lowering pharmacotherapies proven to reduce the risk of atherosclerotic CVD (ASCVD) and reduce the risk of future CVD events. Statins are the lipid-lowering pharmacotherapy of first choice to treat hypercholesterolemia in the vast majority of patients, including patients with diabetes mellitus. However, not all patients are able to achieve recommended LDL-C treatment goals with statins alone. Not all patients are able to tolerate higher doses of statin. Some patients are not able to tolerate any statin treatment. Non-statin lipid-lowering therapies include injectable proprotein convertase subtilisin kexin 9 inhibitors, as well as oral intestinal cholesterol absorption inhibitors, bile acid sequestrants, adenosine triphosphate citrate lyase inhibitors (i.e., bempedoic acid), fibrates, and niacin. This chapter focuses upon intestinal cholesterol inhibitors (i.e., ezetimibe) and bile acid sequestrants/resins (i.e., colesevelam HCl). Ezetimibe blocks the intestinal absorption of both biliary and dietary cholesterol by inhibiting intestinal sterol transporters. Ezetimibe is indicated as monotherapy and in combination with statins to lower LDL-C levels. Ezetimibe also lowers non-high-density lipoprotein (non-HDL) cholesterol, apolipoprotein B, triglycerides, and remnant-like particle cholesterol and modestly raises HDL-C levels. When combined with statins, ezetimibe may also lower C-reactive protein levels. Colesevelam HCl is another gastrointestinal-acting lipid-altering drug classified as a bile acid sequestrant (BAS). BAS (i.e., cholestyramine and colestipol) were among the first drugs approved for lowering cholesterol levels, and clinical outcome trials supported their efficacy in lowering cholesterol blood levels, as well as reducing adverse ASCVD events. Unfortunately, cholestyramine and colestipol were/are poorly tolerated due to gastrointestinal side effects (e.g., nausea, vomiting, intestinal bloating, constipation) and have substantial potential for drug interactions (i.e., impairment of concurrent drug intestinal absorption) that limit their clinical use. Colesevelam HCl was designed to be better tolerated, with less potential for drug interactions. In addition to their lipid effects, BAS also reduce glucose levels. Colesevelam HCl is indicated as a lipid-lowering and anti-diabetes mellitus pharmacotherapy agent.

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  1. Louisville Metabolic and Atherosclerosis Research Center, University of Louisville School of Medicine, Louisville, KY, USA

    Harold Edward Bays

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  1. NHMRC Clinical Trials Centre, University of Sydney, Sydney, NSW, Australia

    Alicia J. Jenkins

  2. Department of Medicine, Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Peter P. Toth

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Bays, H.E. (2023). Cholesterol Absorption Inhibitors (Ezetimibe) and Bile Acid-Binding Resins (Colesevelam HCl) as Therapy for Dyslipidemia in Patients with Diabetes Mellitus. In: Jenkins, A.J., Toth, P.P. (eds) Lipoproteins in Diabetes Mellitus. Contemporary Diabetes. Humana, Cham. https://doi.org/10.1007/978-3-031-26681-2_26

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