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.