The idea that hyperinsulinemia may promote cancer risk is bolstered by the fact that biguanides such as metformin and phenformin, the most commonly prescribed class of diabetes drug worldwide, slow tumor growth associated with reductions in plasma insulin concentrations [18–30], although this class of agents has also shown efficacy in vivo independent of changes in plasma insulin concentrations in a minority of studies [31–33]. This evidence concerns the gene INS and neoplasm.