Phase 3 Studies of Canagliflozin for Type 2 Diabetes

Janssen Research & Development announced results from two Phase 3 clinical studies, DIA3015 and DIA3009, showing that canagliflozin provided substantial and sustained glycemic improvements in adult patients with type 2 diabetes. The studies compared canagliflozin to current standard treatments, Januvia (sitagliptin; Merck & Co.) and Amaryl (glimepiride; Sanofi Aventis); canagliflozin dosed once-daily at 300mg provided significantly greater reductions in A1C levels relative to both comparators.

DIA3015 was a 52-week randomized, double-blind, active-controlled study in 755 adult patients with inadequate glycemic control on maximally effective doses of Glucophage (metformin; Bristol-Myers Squibb) and sulfonylurea. Patients were given once-daily doses of canagliflozin (300mg) or sitagliptin (100mg). Patients treated with canagliflozin had a substantial and sustained decrease in A1C levels, with a significantly greater reduction relative to sitagliptin after 52 weeks (-0.37, 95% CI -0.5; -0.25). In the key secondary endpoint measures, patients treated with canagliflozin 300mg also had greater weight loss compared to sitagliptin (percent changes of -2.5 and 0.3, respectively); reductions in fasting plasma glucose changes were consistent with the primary A1C endpoint (-29.9mg/dL and -5.9mg/dL, respectively); systolic blood pressure was reduced with canagliflozin (-5.1mmHg and 0.9mmHg, respectively). Canagliflozin raised HDL-C relative to sitagliptin (% change, 7.6 and 0.6, respectively), and also LDL-C (% change 11.7 and 5.2, respectively).

DIA3009 was a 52-week randomized, double-blind, active-controlled trial in 1,450 adult patients with inadequate glycemic control on maximally effective doses of metformin. Patients were randomized and treated once daily with either canagliflozin (100mg or 300mg) or glimepiride (with up-titration of glimepiride allowed throughout the 52-week period). Patients treated with canagliflozin had a sustained decrease in A1C, with statistically greater A1C-lowering for canagliflozin 300mg after 52 weeks when compared to glimepiride (-0.93% and -0.81%, respectively, with the between group difference of -0.12%, 95% CI -0.22; -0.02); the decrease in A1C with canagliflozin 100mg (-0.82%) was similar to that for glimepiride (between group difference of -0.01%, 95% CI -0.11; 0.09). In the key secondary endpoint measures, both the 300mg and 100mg canagliflozin dose groups provided reductions in body weight, with no notable change in the glimepiride group (body weight % change, -4.7 and -4.2 and 1, respectively). Reductions in fasting plasma glucose were consistent with the primary endpoint for canagliflozin 300mg and 100mg and glimepiride (-27.5mg/dL and -24.3mg/dL and -18.3mg/dL, respectively); other secondary endpoints included reductions in systolic blood pressure with both doses of canagliflozin and no notable change with glimepiride (-4.6mmHg and -3.3mmHg and 0.2mmHg, respectively); HDL-C increased with both 300mg and 100mg doses of canagliflozin, with no notable change with glimepiride (% change, 9 and 7.9 and 0.3, respectively); LDL-C rose with both doses of canagliflozin more than with glimepiride (% change, 14.1 and 9.6 and 5, respectively).

Canagliflozin is an investigational sodium glucose co-transporter 2 (SGLT2) inhibitor, blocking the reabsorption of glucose in the kidney. The kidneys of patients with type 2 diabetes reabsorb greater amounts of glucose back into the body compared to non-diabetic people, which may contribute to elevated glucose levels.

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