INS and type 2 diabetes mellitus: In several epidemiologic studies, metformin use was associated with a reduced incidence of HCC in T2DM patients.4–6 A comprehensive meta-analysis of 10 studies reported that metformin use was associated with a 50% reduction in the risk of developing HCC, whereas use of sulfonylureas or insulin did not alter the high risk of developing HCC in patients with T2DM.24 Therefore, metformin can be considered a potent inhibitor of de novo tumor development in this carcinogenic environment.