Modulating LDL cholesterol and glucose in patients with type 2 diabetes mellitus: targeting the bile acid pathway

Abstract

Individuals with type 2 diabetes mellitus (T2DM) have a number of potentially modifiable risk factors, including dyslipidemia, hypertension, and hyperglycemia, that contribute to coronary artery disease risk. Elevated low-density lipoprotein cholesterol (LDL-C) is a major contributor to coronary artery disease, and clinical trials have demonstrated significant macrovascular benefits associated with lowering LDL-C in individuals with T2DM, even in those with only a modest LDL-C elevation. Intensive glycemic control has been shown to reduce microvascular complications associated with T2DM. Therefore, it is important to treat both dyslipidemia and hyperglycemia to reduce complications. In this paper, the effect of elevated LDL-C and glucose concentrations on T2DM outcomes is reviewed. Lipid and glucose homeostasis are linked in part through bile acid pathways. Recent clinical trials demonstrate that bile acid sequestrants, which significantly reduce LDL-C, can also significantly reduce glucose levels in patients with T2DM. These findings supported recent Food and Drug Administration approval of the bile acid sequestrant colesevelam HCl for reducing glycemia in patients with T2DM. A multitargeted therapeutic approach using a bile acid sequestrant to improve both cholesterol and glucose management in patients with T2DM may be clinically beneficial.