We found that insulin on top of metformin therapy targets predominantly preglomerular site and increases renal vascular resistance, thereby diminishing renal blood supply, and second that SGLT2-inhibition with empagliflozin impacts predominantly on postglomerular site, decreases renal vascular resistance and preserves renal perfusion in patients with type 2 diabetes and an preserved renal function. The gene discussed is SLC5A2; the disease is type 2 diabetes mellitus.