Now that colesevelam (WelChol), a bile acid sequestrant (BAS), has been shown to decrease hemoglobin A1c (HbA1c), should it be the agent of choice (rather than ezetimibe [Zetia]) in diabetic patients who have not reached their cholesterol goals after using maximum doses of a statin?
—John S. Rajapakse, MD, Woodbridge, N.J.

According to the Adult Treatment Panel III, statins provide a consistent overall mortality benefit when used for primary or secondary prevention of coronary artery disease in diabetic patients (Circulation. 2002;106:3143-3421). The choice of an optimal second agent when a diabetic patient fails the maximum dose of a statin is less clear. Fibrates, ezetimibe, nicotinic acid, and BAS have all been considered, and some remain controversial. Early data regarding BAS did show a reduction in LDL and some coronary heart disease end points but not in overall mortality (JAMA. 1984;251:351-364). More recent studies have shown improved tolerance of BAS and the putative pleiotropic benefits of improved glucose control, e.g., a 0.5% drop in HbA1c (Clin Ther. 2007;29:74-83). Therefore, although randomized, prospective trials comparing the various agents have not been done to fully answer the question, modern BAS can be a good second agent in diabetics who do not reach their LDL goal on maximal statin therapy. The rest of the lipid profile can also help guide the choice of a second agent: A fibrate can help increase HDL <40, and high triglycerides are a relative contraindication to the use of BAS.

Finally, though colesevelam is much better tolerated than its predecessors, it may still cause some mild GI side effects, it can interact with the absorption of certain medications, and patients need to ingest six tablets a day for adequate effect.
—Susan Kashaf, MD, MPH