Inhibiting the IGF1 and PI3K signalling pathways with metformin lowers cellular proliferation in endometrial tumours.69,70 In small window-of-opportunity (presurgery) trials, metformin reduced tumour proliferation (as indicated by the marker Ki-67) by 11.75% (P = 0.008) in patients in one trial and 17.2% (P = 0.002) in another trial, but these findings were not replicated in a confirmatory Phase 3 trial.71–73. This evidence concerns the gene PIK3CA and neoplasm.