James F. List, Jean M. Whaley Kidney International

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Glucose dynamics and mechanistic implications of SGLT2 inhibitors in animals and humans James F. List, Jean M. Whaley Kidney International Volume 79, Pages S20-S27 (March 2011) DOI: 10.1038/ki.2010.512 Copyright © 2011 International Society of Nephrology Terms and Conditions

Figure 1 Dose-dependent glucosuric response of selected SGLT2 inhibitors over 24h per 200g body weight following oral administration in normal rats. Data are not from a single head-to-head study.5,6 Adapted with permission from Meng et al.6 Copyright 2008, American Chemical Society. Kidney International 2011 79, S20-S27DOI: (10.1038/ki.2010.512) Copyright © 2011 International Society of Nephrology Terms and Conditions

Figure 2 Phlorizin increases insulin-mediated glucose uptake in diabetic rats during a two-step euglycemic hyperinsulinemic clamp study. (a) Glucose uptake during insulin infusion rate of 2.4mU/kg·min. (b) Glucose uptake during insulin infusion rate of 4.8mU/kg·min (ref. 10). Kidney International 2011 79, S20-S27DOI: (10.1038/ki.2010.512) Copyright © 2011 International Society of Nephrology Terms and Conditions

Figure 3 Dose-dependent increases in urinary glucose excretion with dapagliflozin or sergliflozin in 64 or 14 healthy volunteers, respectively. (a) Dapagliflozin data;31 copyright 2009, American Society for Clinical Pharmacology and Therapeutics. (b) Sergliflozin data;32 copyright American Diabetes Association. Kidney International 2011 79, S20-S27DOI: (10.1038/ki.2010.512) Copyright © 2011 International Society of Nephrology Terms and Conditions

Figure 4 Urinary glucose excretion in 6 healthy subjects and 16 patients with type 2 diabetes mellitus (T2DM) after 1 and 14 days of treatment with dapagliflozin (100mg). Circles represent observed values and bars represent median values.30 Copyright 2009, American Society for Clinical Pharmacology and Therapeutics. Kidney International 2011 79, S20-S27DOI: (10.1038/ki.2010.512) Copyright © 2011 International Society of Nephrology Terms and Conditions

Figure 5 Mean change in fasting plasma glucose over time in 389 treatment-naive patients with type 2 diabetes mellitus treated with dapagliflozin.38 NS, not significant. Copyright 2009, American Diabetes Association. Kidney International 2011 79, S20-S27DOI: (10.1038/ki.2010.512) Copyright © 2011 International Society of Nephrology Terms and Conditions