Fig. 4.

Effect of sodium-glucose cotransporter (SGLT)2 inhibitors (SGLT2i) on proximal tubule (PT) glucose and Na⁺ reabsorption at normal blood glucose concentrations. A: reduced SGLT2 glucose reabsorption through SGLT2 increases glucose delivery to and reabsorption by SGLT1 (all cases). B: SGLT2 Na⁺ reabsorption is reduced, but since SGLT1 reabsorbs Na⁺ and glucose at a 2-to-1 ratio, SGLT1 Na⁺ reabsorption is greatly increased, so that there is a net Na⁺ increase through SGLT (all cases). C and D: in cases 1 and 2, total PT Na⁺ reabsorption is nearly unchanged. At normal glucose levels, SGLT accounts for only a small fraction of PT Na⁺ reabsorption, so the effect of SGLT2i on total PT Na⁺ reabsorption is small. Na⁺/H⁺ exchanger 3 (NHE3) accounts for the bulk of PT Na⁺ reabsorption. E and F: in cases 3 and 4, when SGLT2 inhibition also triggers NHE3 inhibition, total and fractional PT Na⁺ reabsorption is reduced, primarily because of reduced reabsorption through NHE3.