Metformin inhibits the stabilization of HIF1α in mesothelial cells to impair ovarian cancer invasion.225 Metformin-mediated hypoxia reduction205 enhances the antitumor effect of PD-1 inhibitor in cancer cells.226 Hypoxia may predict who are irresponsive to metformin according to Sivalingam et al.227 They showed that metformin response decreases under hypoxic and hyperglycemia, and that cancer-cell metabolism is reprogrammed toward glycolysis under a hypoxic, high-glucose condition. This evidence concerns the gene HIF1A and cancer.