INS and type 2 diabetes mellitus: Despite these advances, metformin has remained a first-line therapy in many glucocentric algorithms [20] largely due to its antihyperglycemic efficacy, affordability, weight-neutral effects, and the reduction in CV morbidity and mortality observed in a small group of newly diagnosed overweight T2D patients with low CV risk in the UKPDS study when compared to diet, sulfonylureas, or first-generation insulins [21].