Metformin, the traditional first-line drug for T2D, shows significant glucose-lowering and insulin-sensitizing properties by several still incompletely understood mechanisms, including reduction of hepatic gluconeogenesis, stimulation of muscle glucose disposal in muscle, improvement of lipid metabolism by promoting NEFA re-esterification and inhibiting lipolysis and modulating gastrointestinal function (356). The gene discussed is INS; the disease is type 2 diabetes mellitus.