In addition, it has been demonstrated in randomized controlled trials that replacement of sugars with NSSs in the diet can have beneficial effects on cardiometabolic outcomes (e.g., glycated hemoglobin, blood glucose, blood insulin, lipid profile) [3,4,[147], [148], [149]], which suggests hyperglycemia and hyperinsulinemia cannot be a mode of action, as hypothesized by IARC [150]. This evidence concerns the gene INS and Hyperinsulinemia.