Abstract
Bile sequestrants have been used for almost 50 years to lower low density lipoprotein cholesterol (LDL-C). The advent of colesevelam in 2000 provided a more tolerable add-on LDL-C-lowering agent with an excellent safety record and with likely benefit for coronary heart disease events. Colesevelam lowers LDL-C approximately 15%, and has an additive effect when combined with statin or non-statin lipid-modifying agents. It also tends to increase triglyceride levels. The discovery that bile sequestrants also lower glucose levels led to definitive large-scale clinical trials testing the effect of colesevelam as a dual antihyperglycemic agent with LDL-C-lowering properties in type 2 diabetic subjects on metformin-, sulfonylurea- or insulin-based therapy with inadequate glycemic control. Colesevelam was found to lower hemoglobin A1c (HbA1c) by approximately 0.5% compared to placebo over the 16- to 26-week period, and had similar effects on the lipid profile in these diabetic subjects, as had previously been demonstrated in non-diabetic individuals. Colesevelam was well tolerated, with constipation being the most common adverse effect, and did not cause weight gain or excessive hypoglycemia. Colesevelam thus combines antihyperglycemic action with LDL-C-lowering properties, and should be useful in the management of type 2 diabetes.