GPBAR1 and gallstones: For example, gut-restricted TGR5 agonists had been reported to be effectively confined in the gut to induce GLP-1 secretion, as systemic activation of TGR5 is known to stimulate excessive gallbladder filling and cause gallstones (Duan et al., 2015; Cao et al., 2016; Chen et al., 2018).