In preclinical models, metformin was shown to downregulate IGF signalling and inhibit proliferation of uterine serous carcinoma cells.63 Metformin also attenuates the expression of IGF1 and the activation of mTOR and Akt (downstream effectors of insulin signalling) in breast, lung and pancreatic cancer cells.64–66 However, the clinical response to metformin has been mixed. This evidence concerns the gene IGF1 and familial pancreatic carcinoma.