Canagliflozin: Phase III data

The double-blind, international Phase III DIA3009 trial in 1,450 Type II diabetics with inadequate glycemic control on maximally effective doses of metformin showed once-daily 300 mg oral canagliflozin met the primary endpoint of reducing HbA1c from baseline to week 52 vs. glimepiride (0.93% vs. 0.81%). The once-daily 100 mg dose of canagliflozin was non-inferior but not superior to glimepiride on the endpoint (0.82%). On secondary endpoints, low- and high-dose canagliflozin led to significantly greater reductions in body weight (4.2% and 4.7%, respectively, vs. a gain of 1%, p<0.001 for both), the proportion of patients with >=1 episode of hypoglycemia (5.6% and 4.9%, respectively, vs. 34.2%, p<0.001 for both), FPG (24.3 and 27.5 mg/dL, respectively, vs. 18.3 mg/dL) and SBP vs. glimepiride (3.3 and 4.6 mmHg, respectively, vs. a gain of 0.2 mmHg).

Low-dose canagliflozin increased HDL-C by 7.9% and LDL-C by 9.6%, and reduced triglycerides by 3.7% from baseline to week 52; high-dose canagliflozin increased HDL-C by 9%, LDL-C by 14.1% and triglycerides by 2.3; and glimepiride increased each endpoint by 0.3%, 5% and 9.5%, respectively. Canagliflozin was generally well tolerated with a similar incidence of adverse events between treatment groups. Adverse events related to osmotic diuresis and urinary tract infections (UTI) were more frequent in patients treated with canagliflozin compared to glimepiride. Data were presented at the American Diabetes Association meeting in Philadelphia. ...