A review of bile acid sequestrants: potential mechanism(s) for glucose-lowering effects in type 2 diabetes mellitus.
ABSTRACT Clinical evidence has demonstrated that bile acid sequestrants reduce glucose levels in patients with type 2 diabetes mellitus (T2DM). This effect has been confirmed in multiple double-blind, placebo-controlled clinical studies with the bile acid sequestrant colesevelam hydrochloride (HCl). Colesevelam HCl was approved by the US Food and Drug Administration in January 2008 as an adjunctive therapy for patients with T2DM to improve glycemic control. However, the mechanism of action for the glucose-lowering effect of bile acid sequestrants is unclear. Bile acid sequestrants are nonsystemic pharmacological agents that bind bile acids in the gastrointestinal tract, thereby diverting bile acids from the enterohepatic circulation. This, in turn, upregulates bile acid synthesis (via cholesterol 7-alpha-hydroxylase), which utilizes cholesterol, resulting in reduced low-density lipoprotein cholesterol levels. Recent research has revealed that bile acids are tightly controlled signaling molecules that have metabolic effects beyond their primary role in bile to aid in the digestion of lipids and fat. Bile acids signal via various membrane and nuclear receptors. Therefore, bile acid sequestrants may exert glycemic effects by altering the interaction of these bile acid pathways. This article reviews the role for bile acids in glucose regulation and discusses the potential mechanism(s) of action for the glycemic effects of bile acid sequestrants.
- SourceAvailable from: Yehuda HandelsmanDiabetes care 05/2011; 34 Suppl 2:S244-50. · 7.74 Impact Factor
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ABSTRACT: Hypercholesterolemia holds a key role in the development and progression of atherosclerosis and is a causative factor of coronary artery disease. Current guidelines for cholesterol treatment target low-density cholesterol (LDL-C) as the primary goal of therapy. Despite advances in the pharmacotherapy of atherosclerosis, the most successful agents used to treat this disease--HMG CoA reductase inhibitors--remain ineffective for the primary or secondary prevention of myocardial infarction in 50-60% of patients. Advancing therapy for hypercholesterolemia with new-emerging drugs either as monotherapy or in combination will hopefully improve cardiovascular outcomes. The two major sources of cholesterol in the human body are: i) biosynthesis of cholesterol by the liver; and ii) absorption by the intestines. Both play a pivotal role in the overall balance of cholesterol. A recent and more effective therapeutic strategy is to treat both sources of cholesterol simultaneously with a complementary mechanism of action. The present article presents cholesterol metabolism and reviews new emerging lipid-lowering drugs and therapies that: i) lower LDL-C; ii) lower triglycerides; and iii) increase high-density lipoprotein cholesterol. This review summarizes the pivotal role of both the liver and intestine in the overall balance of cholesterol in the body and describe the clinical impact and relevance of using new emerging lipid-lowering drugs either alone or co-administered with statins in controlling cholesterol levels. An elevated concentration of LDL-C plays a causal role in the development of cardiovascular disease. The new aggressive cholesterol treatment goals call for a more advanced therapeutic approach to maximize the cardiovascular benefits associated with lower LDL-C levels.Expert Opinion on Pharmacotherapy 07/2010; 11(10):1659-72. · 2.86 Impact Factor
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ABSTRACT: Hyperglycemia and hyperlipidemia are both risk factors for the development of various complications in patients with type 2 diabetes mellitus. Colesevelam hydrochloride is a novel agent that can improve both hypercholesterolemia and hyperglycemia in such patients. It is an orally administered bile acid sequestrant with high capacity for binding bile acids. This drug can offer potential new diabetes treatment along with other drugs.International journal of applied and basic medical research. 07/2011; 1(2):113-5.