Table 2.
Bile acid-based therapies
| Type of therapy | Effects |
|---|---|
| Bile acid replacement | |
| CDCA | Treats inborn errors of bile acid synthesis; reduces hypertriglyceridemia in gallstone patients |
| UDCA | Dissolves gallstones; reduces bile acid cytotoxicity in circulating pool |
| Bile acid sequestrants (bile acid–binding resins) | |
| Cholestyramine, colesevelam | Dissolves gallstones; treats diabetes but increases triglycerides; stimulates bile acid synthesis (CYP7A1); decreases FGF19; activates TGR5/GLP-1 signaling and improves glycemic control; stimulates thermogenesis in brown adipose tissue |
| FXR agonists | |
| Obeticholic acid, INT-747 (6-ethyl-chenodeoxycholic acid), Ocaliva (Intercept Pharmaceuticals) | Anti-inflammatory; used to treat cholestasis, NASH, diabetes, obesity, and PBC |
| NorUDCA | Used to treat PBC and PSC |
| Fexaramine (intestine-restricted FXR agonist) | Used to treat obesity and diabetes |
| FXR antagonists | |
| UDCA, glycine-MCA | Used to treat obesity and diabetes |
| TGR5 agonists | |
| INT-777 [6α-etdyl-23(S)-metdyl-cholic acid] | Anti-inflammatory; used to treat obesity and NASH |
| Dual FXR and TGR5 agonists | |
| INT-767 (6α-etdyl-3α, 7α, 23-trihydroxy-24-nor-5β-cholan-23-sulfate sodium salt) | Used to treat NASH |
Abbreviations: CDCA, chenodeoxycholic acid; CYP7A1, cholesterol 7α-hydroxylase; FGF, fibroblast growth factor; FXR, farnesoid X receptor; GLP-1, glucagon-like peptide 1; MCA, muricholic acid; NASH, nonalcoholic steatohepatitis; PBC, primary biliary cirrhosis; PSC, primary sclerosing cholangitis; TGR5, Takeda G protein–coupled receptor 5; UDCA, ursodeoxycholic acid.