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Bile Acid Sequestrants and the Treatment of Type 2 Diabetes Mellitus

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Abstract

Bile acids promote bile formation and facilitate dietary lipid absorption. Animal and human studies showing disturbed bile acid metabolism in diabetes mellitus suggest a link between bile acids and glucose control. Bile acids are activating ligands of the farnesoid X receptor (FXR), a nuclear receptor with an established role in bile acid and lipid metabolism. Evidence suggests a role for FXR also in maintenance of glucose homeostasis. Animal and human studies employing bile acid sequestrants (bile acid binding agents), which interrupt the enterohepatic circulation of bile acids and effectively reduce plasma cholesterol, support a link between bile acid and glucose metabolism. In lipid-lowering trials, bile acid sequestrants, such as colesevelam hydrochloride, colestyramine (cholestyramine) and colestilan (colestimide), have also been shown to lower plasma glucose and glycosylated haemoglobin levels, suggesting the utility of these agents as a potential therapy for type 2 diabetes. In this article, we review the relationship between bile acid metabolism and glucose homeostasis, and present data demonstrating the utility of bile acid sequestrants in the management of diabetes.

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Acknowledgements

Bart Staels and Folkert Kuipers were supported by the EU Grant Hepadip (N° 018734). Bart Staels received additional support by a grant from the Agence Nationale de la Recherche (N° A05056GS). Editorial support was provided by Karen Stauffer, PhD and funded by Daiichi Sankyo, Inc.

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Authors and Affiliations

  1. Institut Pasteur de Lille, Lille, France

    Bart Staels

  2. Departement d’Artherosclerose, Inserm U545, Institut Pasteur de Lille, 1 rue Calmette BP245, Lille, F-59019, France

    Bart Staels

  3. Faculty of Pharmaceutical and Biological Sciences and Faculty of Medicine, University of Lille 2, Lille, France

    Bart Staels

  4. Center for Liver, Digestive, and Metabolic Diseases, University Medical Center Groningen, Hanzeplein, The Netherlands

    Folkert Kuipers

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Correspondence to Bart Staels.

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Staels, B., Kuipers, F. Bile Acid Sequestrants and the Treatment of Type 2 Diabetes Mellitus. Drugs 67, 1383–1392 (2007). https://doi.org/10.2165/00003495-200767100-00001

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