High glucose concentrations are recognised to modify the effect of metformin;28,36,37 in breast cancer for example, mTOR inhibition by metformin was diminished in cells cultured in high glucose (11–25 mM).38,39 A shift towards glycolytic energy metabolism and reduced dependence on oxidative phosphorylation has been proposed as a resistance mechanism. The gene discussed is MTOR; the disease is breast carcinoma.