obeticholic-acid and semaglutide

There is an unmet medical need for an effective anti-fibrotic treatment for NASH with advanced fibrosis.. The authors review the current and novel agents for the treatment of NASH with fibrosis. They also consider the potential future strategies of combination therapies.. Farnesoid X receptor (FXR) agonist (obeticholic acid [OCA]) significantly ameliorated hepatic fibrosis in NASH stage 2/3 fibrosis in an interim analysis of phase 3 trial. Because OCA has several drawbacks such as itching and elevated low-density lipoprotein-cholesterol (LDL-C), non-bile acid FXR agonists are now under development. Selonsertib (apoptosis signaling kinase 1 inhibitor), emricasan (an irreversible pan-caspase inhibitor), and simtsuzumab (a monoclonal antibody against lysyl oxidase-like 2) were discontinued because of no efficacy over placebo. Peroxisome proliferator-activator receptor α/δ agonists, C-C motif chemokine receptor-2/5 antagonists, and thyroid β receptor agonist are ongoing in phase 3 trials. A variety of agents including fibroblast growth factor (FGF)-21 and FGF-19 agonists, as well as acetyl-CoA carboxylase inhibitors, are also expected. Among antidiabetic agents, semaglutide, a novel GLP-1 RA, is ongoing for NASH stage 1-3 fibrosis in a phase 2 trial. Furthermore, the combination of GLP-RA/glucagon receptor agonist and GLP-RA/gastrointestinal peptide agonist are promising future options.

Topics: Chenodeoxycholic Acid; Clinical Trials as Topic; Fibroblast Growth Factors; Glucagon-Like Peptides; Humans; Liver Cirrhosis; Non-alcoholic Fatty Liver Disease; Peroxisome Proliferator-Activated Receptors; Pioglitazone; Receptors, Cytoplasmic and Nuclear; Treatment Outcome; Vitamin E