Inhibition by metformin of glucose production via reduced energy potential in the liver. Metformin is transported into hepatocytes by the transporter OCT1. Once inside the cell, it partially inhibits the mitochondrial respiratory chain at complex I, which is its primary target. This leads to a reduction in energy levels in the cell, reflected in lower intracellular ATP levels and corresponding higher AMP levels. Gluconeogensis is an energy-intensive metabolic pathway, requiring 4 ATP and 2 GTP molecules per glucose molecule produced. The reduction in ATP levels in response to metformin therefore reduces glucose production. In addition, the accumulation of AMP allosterically inhibits fructose-1,6-diphosphatase, one of the key gluconeogenesis enzymes, and reduces activation of the adenylate cyclase stimulated by glucagon. The result is slower gluconeogenesis and hence an improvement in hyperglycaemia for type 2 diabetic patients.