The uptake of metformin from circulation into renal epithelial cells is primarily facilitated by OCT2 (gene SLC22A2) [10], which is expressed predominantly at the basolateral membrane in the renal tubules. Renal excretion of metformin from the tubule cell to the lumen is mediated through MATE1 (SLC47A1) and MATE2-K (SLC47A2) [14,15,19,20]. MATE1 and MATE2-K are expressed in the apical membrane of the renal proximal tubule cells, and studies in healthy individuals suggest that they contribute to the renal excretion of metformin [21]. OCT1 also appears to be expressed on the apical and subapical domain side of both the proximal and the distal tubules in the kidney, and may play an important role in metformin reabsorption in kidney tubules [22]. PMAT (gene SLC29A4) is expressed on the apical membrane of renal epithelial cells, and may play a role in the renal reabsorption of metformin [23]. However, there are no in-vivo data as yet supporting this role. In addition, P-gp (gene ABCB1) and BCRP (gene ABCG2) are involved in the efflux of metformin across placental apical membranes [24].