In light of the EMPA-REG Outcome study that showed an early separation of the incidence of hospitalization for heart failure and cardiovascular death between the SGLT-2 inhibitor and the placebo group [6, 36] we want to put forward the hypothesis that whereas the diuretic and natriuretic effect of SGLT-2 inhibition observed in the first days after initiating therapy may acutely decrease preload, even a small natriuretic effect per day may be effected and leads to a reduction of the total skin-sodium content in patients with type 2 diabetes over weeks. Here, SLC5A2 is linked to type 2 diabetes mellitus.