The reason is not clear. A recent study showed that metformin delays the onset of tobacco carcinogen-induced lung tumorigenesis in a non-diabetic mouse model, but the laboratory data are insufficient to translate to humans with diabetes. PPAR-c is a member of the nuclear receptor superfamily. Once activated, it will preferentially bind to retinoid X receptora and signal antiproliferative, antiangiogenic, and prodifferentiation pathways in several tissues. In vitro studies have shown that TZDs induce apoptosis and differentiation for potential chemoprevention in non-small-cell lung cancer, but it is not clear whether these mechanisms are relevant in humans. But epidemiological studies have provided varying results, suggesting either a beneficial or neutral effect on lung ALK5 Inhibitor II cancer risk. Colmers et al. observed in their meta-analysis a 9% decreased risk in the lung cancer subgroup among observational studies. Another meta-analysis of Bosetti et al. showed that the TZDs use was not associated with the lung cancer risk, which included two publications for the same population from Taiwan. Our present meta-analysis included one population of the larger sample from Taiwan and another study from the USA. Our updated evidence did not indicate any relevant role of TZDs use on lung cancer risk either in observational studies or in RCTs. However, the association between TZDs and lung cancer risk was pronounced in the Western population when except for a study from Taiwan. Sulfonylureas seem to promote oncogenesis by increasing insulin secretion, enhancing growth factor-dependent cell RAD001 proliferation and affecting cell metabolism. Epidemiological evidences in lung cancer are conflicting. A previous meta-analysis suggested that sulfonylurea use significantly increases all-cancer risk in patients with type 2 diabetes. Our overall evidence did not indicate any relevant role of sulfonylurea use in lung cancer risk. The result did not change in the Western population, cohort studies or RCTs. The heterogeneous effects of different sulfonylureas may explain it. Preclinical evidence has also shown that glibenclamide has antitumor activity, besides a role in promoting cancer. The role of glibenclamide as a KATP channel inhibitor and its interaction with reactive oxygen species production seem to underlie the proapoptotic and neoangiogenesis effect.