A meta-analysis by Wu et al. compared the metabolic effect of oral contraceptives and combination of oral contraceptives plus metformin in non-obese adult PCOS patients, and concluded that the combination of the two drugs achieved significant reduction of hyperinsulinemia, although the effect was mostly due to hepatic insulin clearance and not to a real reduction in insulin sensitivity, which showed no difference between the two groups [41]. This evidence concerns the gene INS and polycystic ovary syndrome.