Bile Acid Sequestrants

BILE ACID SEQUESTRANTS

Initially developed as a bile acid sequestrant and cholesterol-lowering drug, colesevelam hydrochloride is now approved as an antihyper-glycemic therapy for persons with type 2 diabetes who are taking other medications or have not achieved adequate control with diet and exercise. The exact mechanism of action is unknown but pre-sumed to involve an interruption of the enterohepatic circulation and a decrease in farnesoid X receptor (FXR) activation. FXR is a nuclear receptor with multiple effects on cholesterol, glucose, and bile acid metabolism. Bile acids are natural ligands of the FXR. Additionally, the drug may impair glucose absorption.

Colesevelam is administered as a pill or an oral suspension in a dosage of 1875 mg twice daily or 3750 mg once daily. It is not sys-temically absorbed or modified and is eliminated intact in the feces. In clinical trials, it lowered the hemoglobin A_1c (HbA_1c) concentra-tion about 0.5%, and LDL cholesterol by 15% or more. Side effects include gastrointestinal complaints (constipation, indigestion, flatu-lence). The medication may impair absorption of multiple other medications including fat-soluble vitamins, glyburide, levothyroxine, and oral contraceptives, and should not be used in individuals with hypertriglyceridemia, a history of pancreatitis secondary to hyper-triglyceridemia, or esophageal, gastric, or intestinal disorders.