Poster Presentation Australian Diabetes Society and the Australian Diabetes Educators Association Annual Scientific Meeting 2014

Canagliflozin (CANA) in subjects with type 2 diabetes mellitus (T2DM) inadequately controlled on sulfonylurea (SU) monotherapy: A CANVAS substudy (#321)

Greg Fulcher 1 , David Matthews 2 , Vlado Perkovic 3 , Kenneth W Magaffey 4 , Robert Weiss 5 , Julio Rosenstock 6 , George Capuano 7 , Mehul Desai 7 , Wayne Shaw 7 , Frank Vercruysse 8 , Gary Meininger 7 , Bruce Neal 3
  1. Royal North Shore Hospital, Sydney, NSW, Australia
  2. The Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM) , OXFORD, UK
  3. George Institute for Global Health, Sydney, NSW, Australia
  4. Duke Clinical Research Institute, Durham, NC, USA
  5. Maine Research Associates, Auburn, ME, USA
  6. 6Dallas Diabetes and Endocrine Center at Medical City, Dallas, TX, USA
  7. Janssen Reasearch and Development, Raritan, NJ, USA
  8. Janssen Research & Development, Beerse, Belgium

Within a pre-specified substudy of the Canagliflozin Cardiovascular Assessment Study (CANVAS), we evaluated the efficacy, safety and tolerability of CANA in subjects with T2DM inadequately controlled on SU monotherapy (n = 127; 45 placebo [PBO], 42 CANA 100 mg and 40 CANA 300 mg).  The primary endpoint was change from baseline in HbA1c at week 18.

Meanbaselineage was 65 y, males (57%), HbA1c 8.4%, BMI 29.9 kg/m2, FPG 10.0 mmol/L, systolic blood pressure(SBP) 136.3 mmHg and eGFR 69.3 mL/min/1.73 m2.  At randomization, 35% were taking glimepiride, 29% glyburide/glibenclamide and 27% gliclazide modified release (ND).  Compared to PBO, both CANA doses significantly improved glycemia(Table).  The overall incidence of adverse events (AEs) with CANA 100 mg (26.2%) was lower relative to PBO (64.4%) and CANA 300 mg (45%).  Specific AEs of male and female genital infections, pollakiuria, and thirst were more common with CANA.  AEs leading to discontinuation in the CANA groups were low (300 mg; 2.5%, 100 mg; 2.4%), with none reported in the PBO group.  Documented hypoglycemia was similar with CANA 100 mg (4.1%) and PBO (5.8%) and higher with CANA 300 mg (12.5%).  There were no severe hypoglycemic episodes.  In conclusion, CANA added to ongoing SU monotherapy produced significant improvements in a number of efficacy parameters important in T2DM management with an increased incidence of several specific AEs probably related to SGLT2 inhibition.