Collectively, these findings have prompted the development of dual GPBAR1/FXR agonists as a new frontier in the pharmacological treatment of hypercholesterolemia, hypertriglyceridemia, and type II diabetes (Fiorucci et al., 2009; Fiorucci and Distrutti, 2015; Sepe et al., 2015b). This evidence concerns the gene NR1H4 and type 2 diabetes mellitus.