Here, we characterize RDX8940 (formerly RDX009-01), a novel, orally administered TGR5 agonist designed to be minimally systemic, potent, and selective, and investigate its effects in mice fed a Western diet, a model of NAFLD, and mild insulin resistance, to determine its potential therapeutic value to patients with metabolic diseases, such as NAFLD/NASH. This evidence concerns the gene GPBAR1 and Insulin resistance.