GPBAR1 and type 2 diabetes mellitus: Other approaches include bile-acid sequestrants, such as colesevelam: Originally licensed for hypercholesterolemia, colesevelam also lowers HbA1c levels by ~0.5 percentage points in type 2 diabetes, as demonstrated in the GOAL-RCT [154]—likely by interrupting enterohepatic cycling (forcing de novo bile-acid synthesis, which consumes hepatic glucose) and/or by enhancing GLP-1 release through TGR5 activation.