We sought to better delineate the effects of the combination of metformin with afatinib in EGFR-mutated NSCLC cell lines; to carry out this objective, our investigation identified a synergic cytotoxicity and apoptosis in all the different lung cancer cell lines after using afatinib–metformin combination, as metformin effects on non-transformed cells include inhibition of liver gluconeogenesis, increase and acceleration of glucose uptake, and stimulation of insulin receptors (IRs) [23,24,25]. This evidence concerns the gene IARS1 and lung cancer.