Synthetic FXR and TGR5 agonists have been developed to serve as next-generation drugs for the treatment of metabolic diseases and cholestatic liver disease (Figure 3).37,76,122,123 Of note, these drugs undergo enterohepatic cycling and will be most effective in liver and intestine. Apical sodium-dependent bile salt transporter (ASBT, also known as ileal sodium/bile acid cotransporter or SLC10A2) inhibitors and bile salt sequestrants (discussed later) are developed as possible drugs for treatment of hypercholesterolaemia, cholestatic liver disease and T2DM.124 In addition, colestyramine, originally developed for treatment of hypercholesterolaemia, improves insulin sensitivity and causes weight loss; as such, colestyramine, colesevalam and other sequestrants are being re-investigate d for treatment of T2DM.125
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