Over 30 years ago,
bile acid sequestrants (BAS) were among the first drugs approved to lower
cholesterol levels. For over 10 years, BAS have been known to reduce
glucose levels. Most importantly, BAS have been shown in outcomes studies to reduce cardiovascular events. Because they are true nonsystemic agents, BAS are generally safe and not associated with serious systemic adverse experiences. Despite their proven atherosclerotic
coronary heart disease (CHD) benefits, and irrespective of their favorable effects on major CHD risk factors (
hypercholesterolemia and
hyperglycemia), BAS are not among the more frequently used
drug treatments for
hypercholesterolemia, even in patients with
type 2 diabetes mellitus. Recent "high-profile" findings of investigational and approved
lipid-altering and antidiabetes
drug therapies illustrate that
drug-induced improvements in
lipid and
glucose levels do not always reduce CHD risk. It may therefore be time to reconsider the clinical use of BAS. This review focuses on the recent lessons learned, and the potential mechanisms involved in efficacy and safety issues raised with
torcetrapib and
rosiglitazone with analogies related to the use of BAS
therapy. Known and proposed mechanisms of how BAS may improve
lipid and
glucose levels are discussed, which are effects that may help explain how BAS reduce CHD risk. Improved tolerability of newer BAS (eg,
colesevelam hydrochloride) and a "new" appreciation of the historic benefits of these "old" therapeutic agents may lead to an increased treatment role for these drugs, particularly in hypercholesterolemic patients with
type 2 diabetes mellitus.