In line with this hypothesis, intriguingly, it has been demonstrated that drugs acting on insulin resistance, (i.e., glitazones), were non-effective or deleterious in clinical and experimental studies on HF, whereas glucose lowering drugs with no direct effect on insulin sensitivity [i.e., sodium-glucose co-transporter-2 (SGLT2) inhibitors] have recently proved to be effective in reducing mortality and hospitalization in patients with HF [45, 46]. This evidence concerns the gene INS and Insulin resistance.