Canagliflozin: Phase III data

The double-blind, international Phase III DIA3005 trial in 584 Type II diabetics inadequately controlled with diet and exercise showed that once-daily 100 and 300 mg oral canagliflozin each met the primary endpoint of reducing HbA1c from baseline to week 26 vs. placebo (placebo-adjusted reductions of 0.91% and 1.16%, respectively, p<0.001 for both). On secondary endpoints, low- and high-dose canagliflozin led to significantly greater placebo-adjusted reductions in FPG (1.97 and 2.41 mmol/L, p<0.001 for both), 2-hour post-prandial plasma glucose (2.67 and 3.55 mmol/L, p<0.001 for both), body weight (2.2% and 3.3%, p<0.001 for both) and SBP (3.71 and 5.42 mmHg, p<0.001 for both). Additionally, a significantly greater proportion of patients receiving low- and high-dose canagliflozin achieved an HbA1c target of <7% vs. placebo (placebo-adjusted percentages of 23.9% and 41.7%, respectively, p<0.001 for both).

Furthermore, low-dose canagliflozin led to a placebo-adjusted increase in HDL-C of 6.8% from baseline to week 26, while high-dose canagliflozin led to a placebo-adjusted increase in HDL-C of 6.1% (p<0.001 and p<0.01, respectively). Placebo-adjusted reductions in triglycerides were 5.4% for low-dose canagliflozin and 10.2% for high-dose canagliflozin. Canagliflozin was generally well tolerated, but led to a higher incidence of adverse events vs. placebo (61% and 60%, respectively, vs. 49%). Rates of genital mycotic infections, osmotic diuresis and urinary tract infections (UTI) were higher in patients treated with canagliflozin compared to placebo. Data were presented at the American Diabetes Association meeting in Philadelphia. ...