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Context  The discovery and characterization of the bile acid specific receptors farnesoid X receptor (FXR) and Takeda G protein-coupled receptor 5 (TGR5) have facilitated a wealth of research focusing on the link between bile acid physiology and glucose metabolism. Modulation of FXR and TGR5 activation have been demonstrated to affect the secretion of glucagon-like peptide 1, insulin, and glucagon as well as energy expenditure and gut microbiota composition, with potential beneficial effects on glucose metabolism.    Evidence Acquisition  A search strategy based on literature searches in on PubMed with various combinations of the key words FXR, TGR5, agonist, apical sodium-dependent bile acid transporter (ASBT), bile acid sequestrant, metformin, and glucose metabolism has been applied to obtain material for the present review. Furthermore, manual searches including scanning of reference lists in relevant papers and conference proceedings have been performed.    Evidence Synthesis  This review provides an outline of the link between bile acid and glucose metabolism, with a special focus on the gluco-metabolic impact of treatment modalities with modulating effects on bile acid physiology; including FXR agonists, TGR5 agonists, ASBT inhibitors, bile acid sequestrants, and metformin.    Conclusions  Any potential beneficial gluco-metabolic effects of FXR agonists remain to be established, whereas the clinical relevance of TGR5-based treatment modalities seems limited because of substantial safety concerns of TGR5 agonists observed in animal models. The glucose-lowering effects of ASBT inhibitors, bile acid sequestrants, and metformin are at least partly mediated by modulation of bile acid circulation, which might allow an optimization of these bile acid–modulating treatment modalities. (J Clin Endocrinol Metab 106: 362–373, 2020)

Gluco-Metabolic Effects of Pharmacotherapy-Induced Modulation of Bile Acid Physiology