Although many efforts have been made to develop selective FXR or TGR agonists with reduced side effects, research shows that dual agonism of FXR and TGR5 is extremely useful in the treatment of diabetes mellitus, obesity [76], NASH [55, 77], atherosclerosis [78], and even other diseases like bone loss [79]. This evidence concerns the gene NR1H4 and obesity due to melanocortin 4 receptor deficiency.