Colesevelam hydrochloride: a bile acid sequestrant for glycemic control and treatment of dyslipidemia in Type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) affects approximately 3% of the world’s population (estimate by WHO). The prevalence of T2DM in the USA appears to be increasing due to multiple factors, including changes in diet, decrease in activity levels and obesity [1]. The National Institutes of Health and Centers for Disease Control estimate that over 30% of individuals with T2DM may be undiagnosed. The major complications of T2DM include both micro vascular diseases and macrovascular changes [2,3]. Examples of microvascular complications include retinopathy, neuropathy, nephropathy and macular changes. Patients with T2DM have an increased risk of macrovascular diseases such as coronary artery disease, stroke or peripheral vascular disease [2,3]. The incidence of cardiovascular diseases in T2DM patients is relatively higher than in patients without diabetes [4]. In 2007, the estimated cost of treating diabetics in the USA was nearly equivalent to one in ten of the dollars spent on healthcare [5]. Hence, T2DM is a major health and economic concern in the USA and worldwide. There is a well-established direct relationship that exists between the degree of glycemic control and the risk of microvascular complications [2,6,7]. The primary goal of antidiabetes therapy is to maintain plasma glucose levels as close to normal as possible to minimize microvascular complications, without unacceptable side effects – particularly hypoglycemia. The American Diabetes Association recommends a glycated hemoglobin A1c (HbA1c) goal of less than 7.0%, the level at which clinical trials have demonstrated that the incidence of longterm microvascular complications is reduced [8]. However, a significant number of patients have not achieved this goal [1,9]. In addition to hyperglycemia, patients with T2DM may have associated lipid abnormalities. Lipid abnormalities may include elevated lowdensity lipoprotein cholesterol (LDL-C) levels, elevated triglyceride (TG) levels and decreased high-density lipoprotein cholesterol (HDL-C) levels. An elevated level of LDL-C is currently considered to be a major risk factor for macrovascular diseases [3]. Although low HDL-C and high TG levels are considered to be hallmarks of diabetic dyslipidemia, the American Diabetes Association recommends a primary LDL-C goal of less than 100 mg/dl for individuals without overt cardiovascular disease and T2DM, and an LDL-C goal of less than 70 mg/dl for those with overt cardiovascular disease and T2DM [8]. However, Kennedy et al. demonstrated in a community-based setting that only 49.4% had LDL-C concentrations less than 100 mg/dl, and only 15.7% achieved the more demanding LDL-C goal of less than 70 mg/dl, with 25% of patients requiring more than two lipid-lowering drugs at maximal doses to attain this goal [10]. Treatment of T2DM must be aimed at treating hyperglycemia to prevent microvascular complications (retinopathy, neuropathy and The complications of Type 2 diabetes mellitus (T2DM) include increased risk of macrovascular diseases such as coronary artery disease, stroke or peripheral vascular disease, and microvascular diseases such as retinopathy, neuropathy and nephropathy. The risk of macrovascular and microvascular diseases increases with the presence of dyslipidemia and hyperglycemia, respectively. Hence, treatment of T2DM must be aimed at treating hyperglycemia to prevent microvascular disease and dyslipidemia to prevent macrovascular complications. Recent clinical studies indicate that colesevelam hydrochloride, a bile acid sequestrant, appears to be promising as an add-on therapy for T2DM patients in reducing the hyperglycemia and dyslipidemia. The objective of the paper is to review the efficacy and safety of colesevelam hydrochloride in reducing both low-density lipid cholesterol and glycosylated hemoglobin A1c levels in T2DM patients when combined with metformin, sulfonylurea or insulin.