Fig. 2

Theoretical schema of the underlying mechanism of SGLT2 inhibitors in patients with and without renal dysfunction. In early diabetes, patients do not show renal dysfunction, and glomerular hypertension due to hyperfiltration is generally observed. In this period, interstitial injury around the proximal tubule is typically only mild, and peritubular glucose and AGEs accumulation (represented by small red circles) is often limited (left panel). In more advanced periods of diabetes, glomerular damage becomes more pronounced and GFR also decreases. Accumulation of glucose and AGEs to the tubulo-interstitial tissue advances, and tubulo-interstitial damage and fibrosis progress (right panel)