Dapagliflozin saxagliptin and metformin, triple therapy, success in Phase III trial for type 2 diabetes- AstraZeneca

AstraZeneca announced positive results from a Phase III study comparing the efficacy and safety of dapagliflozin versus placebo as an add-on to saxagliptin and metformin immediate release (IR) in adults with type 2 diabetes who had inadequate glycaemic control (baseline HbA1c 7% - 10.5%).The study met its primary endpoint, with patients receiving the investigational triple combination of dapagliflozin 10 mg, saxagliptin 5 mg and metformin achieving significantly greater mean reductions in HbA1c compared to those treated with placebo, saxagliptin 5 mg and metformin at 24 weeks (�0.82% vs. -0.10%, respectively; p-value<0.0001). the results were presented as an oral presentation (#105-or) at the 75th scientific sessions of the american diabetes association (ada) in boston.>

Among secondary endpoints, the dapagliflozin combination group achieved a significantly greater adjusted mean reduction from baseline in two-hour postprandial glucose (-74 mg/dL vs -38 mg/dL, respectively; p-value<0.00011 and fasting plasma glucose versus the placebo group (-33 mg dl vs -5 mg dl, respectively; p-value><0.0001). more patients in the dapagliflozin combination group also achieved a hba1c level of less than 7% compared to patients in the placebo group at week 24 (38% vs 12%, respectively, p-value><0.0001). in addition, patients in the dapagliflozin combination group had a greater reduction in weight (mean -1.9 kg vs -0.4 kg, respectively; p-value><0.0001) than those in the placebo group. adverse events were similar across treatment groups. the most common adverse events were headache, urinary tract infection, influenza and genital infections. the rate of hypoglycaemia was 1.3% in the dapagliflozin combination group and 0.0% in the placebo group.>

Comment: AstraZeneca has filed a New Drug Application (NDA) with the FDA for the approval of an investigational fixed-dose combination of saxagliptin and dapagliflozin for the treatment of type 2 diabetes and the Prescription Drug User Fee Act (PDUFA) goal date will be in the fourth quarter of 2015.