Colesevelam as an Add-On Treatment for Control of Dyslipidemia and Hyperglycemia in Type 2 Diabetes.

Abstract

Bile acid sequestrants (BASs) have been in use for decades to lower cholesterol. Their low-density lipoprotein (LDL)-lowering effect is the result of binding to and increasing excretion of bile acids, thereby decreasing bile acid return to the liver in the enterohepatic circulation ( 1 Bays H. Dujovne C. Colesevelam HCl: A non-systemic lipid-altering drug. Expert Opin Pharmacother. 2003; 4: 779-790 PubMed Google Scholar ). The liver recovers cholesterol to produce more bile acids by increasing LDL receptor expression, resulting in a drop in plasma LDL cholesterol (LDL-C) levels, typically in the range of 15% to 20% when added to a statin. Earlier generation BASs still in use include cholestyramine and colestipol. In the early 2000s, a second-generation BAS with higher potency in binding bile acids and better tolerability, colesevelam, was introduced, and it became available in Canada in 2012. As suggested in an earlier study of cholestyramine ( 2 Garg A. Grundy S.M. Cholestyramine therapy for dyslipidemia in non-insulin-dependent diabetes mellitus: A short-term, double-blind, crossover trial. Ann Intern Med. 1994; 121: 416-422 Crossref PubMed Scopus (160) Google Scholar ), an additional effect of colesevelam is glucose lowering, with standard doses lowering glycated hemoglobin (A1C) by an average of 0.5% ( 3 Brietzke S.A. Oral antihyperglycemic treatment options for type 2 diabetes mellitus. Med Clin North Am. 2015; 99: 87-106 Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar ). The glucose-lowering effect of colesevelam is recognized in the most recent Canadian guidelines for treatment of dyslipidemia in patients with diabetes ( 4 Mancini G.B. Hegele R.A. Leiter L.A. Dyslipidemia. Can J Diabetes. 2013; 37: S110-16 Abstract Full Text Full Text PDF Scopus (10) Google Scholar ) and the 2015 American Diabetes Association Standards of Medical Care in Diabetes ( 5 American Diabetes Association Seven approaches to glycemic treatment. Diabetes Care. 2015; 38: S41-8 Crossref PubMed Scopus (169) Google Scholar ). Here, we review the evidence regarding the clinical efficacy and safety of colesevelam in patients with type 2 diabetes who have dyslipidemia, and we discuss the proposed mechanisms for improved glycemic control when using this agent.