Sodium Glucose Cotransporter 2 Inhibition in the Diabetic Kidney

An Update

Aleksandra Novikov; Volker Vallon


Curr Opin Nephrol Hypertens. 2016;25(1):50-58. 

In This Article

Why do Sodium Glucose Cotransporter 2 Inhibitors Only Excrete 50–60% of the Filtered Glucose?

If SGLT2 reabsorbs ~97% of filtered glucose, then it is surprising that humans treated with SGLT2 inhibitors only excrete 50–60% of the filtered glucose.[4] This is mimicked in SGLT2 knockout mice, in which mean fractional glucose excretion was 64%.[7] Studies in SGLT1−/− mice have indicated that SGLT2 inhibition strongly increases SGLT1-mediated glucose reabsorption,[21] and demonstrated that the increase in SGLT1-mediated glucose reabsorption fully explained the fractional glucose reabsorption of 40–50% during SGLT2 inhibition in euglycemic mice[11] (Fig. 2). Recent studies further indicated that the SGLT2 inhibitors reach their target mostly through glomerular filtration and from the luminal side.[11,22]