Perhaps it is time to consider that, as with any drug, there is a metformin dose range that is without any effect, one corresponding to “diabetobiguanides” with a pharmacological effect (e.g., insulin sensitization in type 2 diabetes, prevention of insulin-dependent carcinogenesis, indirect inhibition of insulin- and growth factor-dependent cancer growth) but with minimal toxicity and another corresponding to “oncobiguanides” with pharmacological (i.e., direct and strong anti-cancer activity) as well as toxic effects (Fig. 1, top). The gene discussed is INS; the disease is type 2 diabetes mellitus.