Volume 26, Issue 1, Pages 27-38 (July 2017) Sodium-Glucose Co-transporters and Their Inhibition: Clinical Physiology  Ele Ferrannini  Cell Metabolism  Volume 26, Issue 1, Pages 27-38 (July 2017) DOI: 10.1016/j.cmet.2017.04.011 Copyright © 2017 Elsevier Inc. Terms and Conditions

Figure 1 Renal Glucose Reabsorption Renal glucose absorption and excretion in 66 patients with type 2 diabetes at baseline (dotted lines) and after single-dose administration of empagliflozin (25 mg) (full lines). Data recalculated from Ferrannini et al., 2014. The lines are best fits, with the following parameters: baseline [absorption] = −717 + 173 × ln[filtered glucose], (p < 0.0001); baseline ln[excretion] = −3.5 + 0.018 × [filtered glucose], (p < 0.0001); SGLT2i [absorption] = −2.43 + 0.55 × [filtered glucose], (p < 0.0001); SGLT2i [excretion] = 2.43 + 0.44 × [filtered glucose], (p < 0.0001). Cell Metabolism 2017 26, 27-38DOI: (10.1016/j.cmet.2017.04.011) Copyright © 2017 Elsevier Inc. Terms and Conditions

Figure 2 Creatinine Clearance and SGLT2i-Induced Fractional Glucose Excretion Creatinine clearance and fractional glucose excretion during 4-week treatment with 25 mg empagliflozin in lean (BMI = 23.8 kg/m2), overweight (BMI = 28.0 kg/m2), and obese subjects (BMI = 34.7 kg/m2). Data plots are median and 95% confidence intervals (recalculated from data in Ferrannini et al., 2017). ∗p < 0.01 versus lean. Cell Metabolism 2017 26, 27-38DOI: (10.1016/j.cmet.2017.04.011) Copyright © 2017 Elsevier Inc. Terms and Conditions

Figure 3 Principal Metabolic and Hemodynamic Effects of SGLT2 Inhibition Schematic representation of the main metabolic and hemodynamic effects of SGLT2-induced inhibition of renal glucose reabsorption in humans. GFR, glomerular filtration rate; BP, blood pressure; PV, plasma volume; EGP, endogenous glucose production; Lip Ox, lipid oxidation; TGD, tissue glucose disposal; β-OH-B, β-hydroxybutyrate. Red boxes stand for decrease and green boxes for increase; red lines imply a negative effect, green lines a positive one. Cell Metabolism 2017 26, 27-38DOI: (10.1016/j.cmet.2017.04.011) Copyright © 2017 Elsevier Inc. Terms and Conditions

Figure 4 Relation of Glucose Oxidation and β-Hydroxybutyrate Levels to Lipid Oxidation Reciprocal relationship between glucose and lipid oxidation, and direct association of lipid oxidation with circulating β-hydroxybutyrate concentrations. Plots are mean groups values from 65 patients with type 2 diabetes and 13 nondiabetic subjects during a 5-hr mixed meal at baseline and following acute (single administration) and chronic (4 weeks) administration of 25 mg empagliflozin (recalculated from data in Ferrannini et al., 2014 and Ferrannini et al., 2016a). Cell Metabolism 2017 26, 27-38DOI: (10.1016/j.cmet.2017.04.011) Copyright © 2017 Elsevier Inc. Terms and Conditions