Beyond the plausible finding that use of insulin increased risk of liver cancer,[44] another explanation is that metformin is a first-line ADM prescribed in less severe or shorter duration of DM, while insulin is usually prescribed to patients with longer duration and more advanced DM, which in turn may be associated with higher risk of liver cancer.[49] However, when compared to nonuser of any ADM (mild or newly diagnosed DM patients), monotherapy use of metformin achieved a 38% (OR = 0.62; 95% CI, 0.40–0.98) reduction in ratio of liver cancer, probably reflecting the real world scenario. This evidence concerns the gene INS and diabetes mellitus.