With regard to molecular mediators of the colesevelam effect on glucose metabolism, there is considerable evidence emerging about the role of bile acids and nuclear transcription factors, such as the farnesyl X receptor (FXR), in the regulation of glucose and lipid metabolism (7) (8) (9-15). Changes in cellular lipids or nuclear hormone receptors might directly alter HGP although mechanisms leading to changes in hepatic lipid and glucose metabolism by colesevelam HCl have not previously been investigated.