Colesevelam: an improved bile acid sequestrant for treating hypercholesterolemia and improving diabetes

There is a well-established association between serum cholesterol and coronary heart disease. Statins are the first-line agents for the treatment of hypercholesterolemia, yet combination therapy is required to achieve the desired reduction in low-density lipoprotein cholesterol (LDL-C). Niacin and bile acid sequestrants were among the first lipid-lowering drugs developed to lower LDL-C and have been established to be effective both in monotherapy and in combination therapy. However, tolerability and compliance issues have limited their use. Colesevelam HCl is the newest bile acid sequestrant and reduces LDL-C by 16-22% in monotherapy and adds 12-14% in combination dual therapy with statins, fibrates and ezetimibe or in triple therapy with statin and ezetimibe. It reduces C-reactive protein levels by 16-19% in monotherapy or by 23% in combination with statins and other lipid-lowering therapies. In addition, it consistently reduces hemoglobin A_1c by 0.5% in addition to other hypoglycemic drugs in studies of patients with diabetes. Compared with other bile acid sequestrants it has a higher bile acid-binding capacity, reduced adverse effects and, therefore, has better compliance. Colesevelam HCl is thus a useful addition to the lipid-lowering formulary as a second-line agent, particularly for patients with metabolic syndrome requiring extra reduction in LDL-C.