The hepatic uptake of metformin is mediated primarily by OCT1 (SLC22A1) and possibly by OCT3 (SLC22A3). Both transporters are expressed on the basolateral membrane of hepatocytes [6,10–12]. In Oct1-deficient mice, the hepatic metformin concentration in the liver is significantly lower than that in control mice, suggesting that OCT1 is essential for the hepatic uptake of metformin [13]. In addition, the glucose-lowering effects of metformin were completely abolished in the Oct1-deficient mice. Metformin is also a good substrate for human multidrug and toxin extrusion 1 (MATE1, encoded by the gene SLC47A1) and MATE2-K (gene SLC47A2) [10,14–16]. MATE1 (SLC47A1) is highly expressed in the liver, kidney, and skeletal muscle [17], and may contribute toward the excretion of metformin from both the liver and the kidney. However, the role of MATE1 in hepatic secretion has been questioned, as biliary excretion of metformin seems to be insignificant in humans [6]. Data from a Mate1 knockout mouse study suggest that, at least in rodents, biliary excretion of metformin occurs [18].