Impact of Age and Estimated Glomerular Filtration Rate on the Glycemic Efficacy and Safety of Canagliflozin: A Pooled Analysis of Clinical Studies Richard.

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Impact of Age and Estimated Glomerular Filtration Rate on the Glycemic Efficacy and Safety of Canagliflozin: A Pooled Analysis of Clinical Studies Richard E. Gilbert, MD, PhD, FRCPC, Matthew R. Weir, MD, Paola Fioretto, MD, PhD, Gordon Law, PhD, Mehul Desai, MD, Irina Kline, MD, Wayne Shaw, DSL, Gary Meininger, MD Canadian Journal of Diabetes Volume 40, Issue 3, Pages 247-257 (June 2016) DOI: 10.1016/j.jcjd.2015.11.005 Copyright © 2015 Canadian Diabetes Association Terms and Conditions

Figure 1 Differences (95% CIs) between canagliflozin 100 mg and 300 mg vs. placebo in the change in A1C from baseline by subgroup (LOCF). A1C, glycated hemoglobin; BMI, body mass index; CANA, canagliflozin; CI, confidence interval; eGFR, estimated glomerular filtration rate; LOCF, last observation carried forward; PBO, placebo. Canadian Journal of Diabetes 2016 40, 247-257DOI: (10.1016/j.jcjd.2015.11.005) Copyright © 2015 Canadian Diabetes Association Terms and Conditions

Figure 2 Change in A1C levels by sex (LOCF). A1C, glycated hemoglobin; CANA, canagliflozin; CI, confidence interval; LOCF, last observation carried forward; LS, least squares; PBO, placebo; SE, standard error. Canadian Journal of Diabetes 2016 40, 247-257DOI: (10.1016/j.jcjd.2015.11.005) Copyright © 2015 Canadian Diabetes Association Terms and Conditions

Figure 3 Change in A1C by baseline BMI (LOCF). A1C, glycated hemoglobin; BMI, body mass index; CANA, canagliflozin; CI, confidence interval; LOCF, last observation carried forward; LS, least squares; PBO, placebo; SE, standard error. Canadian Journal of Diabetes 2016 40, 247-257DOI: (10.1016/j.jcjd.2015.11.005) Copyright © 2015 Canadian Diabetes Association Terms and Conditions

Figure 4 Change in A1C by age at baseline (LOCF). A1C, glycated hemoglobin; CANA, canagliflozin; CI, confidence interval; LOCF, last observation carried forward; LS, least squares; PBO, placebo; SE, standard error. Canadian Journal of Diabetes 2016 40, 247-257DOI: (10.1016/j.jcjd.2015.11.005) Copyright © 2015 Canadian Diabetes Association Terms and Conditions

Figure 5 Change in A1C by baseline eGFR (LOCF). A1C, glycated hemoglobin; CANA, canagliflozin; CI, confidence interval; eGFR, estimated glomerular filtration rate; LOCF, last observation carried forward; LS, least squares; PBO, placebo; SE, standard error. Canadian Journal of Diabetes 2016 40, 247-257DOI: (10.1016/j.jcjd.2015.11.005) Copyright © 2015 Canadian Diabetes Association Terms and Conditions

Figure 6 Placebo-subtracted LS mean changes in A1C by age at baseline and baseline eGFR (LOCF). A1C, glycated hemoglobin; CANA, canagliflozin; CI, confidence interval; eGFR, estimated glomerular filtration rate; LOCF, last observation carried forward; LS, least squares; PBO, placebo; SE, standard error. aUnit of mL/min/1.73 m2 for eGFR. Canadian Journal of Diabetes 2016 40, 247-257DOI: (10.1016/j.jcjd.2015.11.005) Copyright © 2015 Canadian Diabetes Association Terms and Conditions

Supplementary Figure A1 Differences (95% CIs) between canagliflozin 100 mg and 300 mg vs. placebo in the change in systolic BP from baseline by subgroup (LOCF). BMI, body mass index; BP, blood pressure; CANA, canagliflozin; CI, confidence interval; eGFR, estimated glomerular filtration rate; LOCF, last observation carried forward; PBO, placebo. Canadian Journal of Diabetes 2016 40, 247-257DOI: (10.1016/j.jcjd.2015.11.005) Copyright © 2015 Canadian Diabetes Association Terms and Conditions

Supplementary Figure A2 Placebo-subtracted LS mean changes in systolic BP by age at baseline and baseline eGFR (LOCF). BP, blood pressure; CANA, canagliflozin; CI, confidence interval; eGFR, estimated glomerular filtration rate; LOCF, last observation carried forward; LS, least squares; PBO, placebo. aUnit of mL/min/1.73 m2 for eGFR. Canadian Journal of Diabetes 2016 40, 247-257DOI: (10.1016/j.jcjd.2015.11.005) Copyright © 2015 Canadian Diabetes Association Terms and Conditions