Metformin is considered as a hepatic insulin sensitizer/mimicker, but diminishes hepatic gluconeogenesis by directly inhibiting key mitochondrial enzymes23 or respiratory factors needed to generate ATP required for gluconeogenesis,24 rather than by correcting T2DM‐induced increases in gluconeogenic enzymes; in fact, metformin may self‐limit its effectiveness thereupon by activating hepatic aPKC.25, 26. This evidence concerns the gene INS and type 2 diabetes mellitus.