Bile acid sequestrants: more than simple resins.

Bile acid sequestrants (BAS) have been used for more than 50 years in the treatment of hypercholesterolemia. The last decade, bile acids are emerging as integrated regulators of metabolism via induction of various signal transduction pathways. Consequently, BAS treatment may exert unexpected side-effects. We discuss a selection of recently published studies that evaluated BAS in several metabolic diseases. Recently, an increasing body of evidence has shown that BAS in addition to ameliorating hypercholesterolemia are also effective in improving glycemic control in patients with type 2 diabetes, although the mechanism is not completely understood. Furthermore, some reports suggested using these compounds to modulate energy expenditure. Many of these effects have been related to the local effects of BAS in the intestine by directly binding bile acids in the intestine or indirectly by interfering with signaling processes. A substantial effort is being made by researchers to fully define the mechanism by which BAS improve glycemic control in type 2 diabetic patients. A new challenge will be to confirm in clinical trials the recent discoveries coming from animal experiments suggesting a role for bile acids in energy metabolism.