Data in oral presentation demonstrate that the investigational combination of dapagliflozin, saxagliptin and metformin resulted in statistically significant reductions in HbA1c in patients uncontrolled on saxagliptin and metformin

6 June 2015

AstraZeneca today 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%).1 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).1 The results were presented today as an oral presentation (#105-OR) at the 75th Scientific Sessions of the American Diabetes Association (ADA) in Boston.

"In this study, when dapagliflozin was added to saxagliptin and metformin, patients demonstrated greater HbA1C reductions than those in the placebo and metformin group,"  said lead investigator Chantal Mathieu, MD, PhD, Chair of Endocrinology at the University Hospital Gasthuisberg Leuven, Belgium. "With nearly 50% of type 2 diabetes patients estimated to be uncontrolled on metformin, new treatment approaches are needed, and these data add to the growing body of knowledge for combination therapies."

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<0.0001)1 and fasting plasma glucose versus the placebo group (-33 mg/dL vs -5 mg/dL, respectively; p-value<0.0001).1 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).1 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)1 than those in the placebo group. Adverse events were similar across treatment groups. The most common adverse events (≥ 5%) 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.1

Elisabeth Björk, Vice President, Head of Cardiovascular and Metabolic Diseases, Global Medicines Development, AstraZeneca, said: "We are focused on investigating combination therapies with complementary mechanisms of action and our broad diabetes portfolio positions us well in this area.These positive results reinforce our belief that combination therapies have the potential to be used as early add-on therapy to help patients with type 2 diabetes achieve their treatment goals."

The study included an open-label lead-in period in which patients on metformin (baseline HbA1c 8.0%–11.5%) received open-label saxagliptin 5 mg and metformin for 16 weeks, while patients on metformin and any DPP-4 inhibitor (baseline HbA1c 7.5%–10.5%) received open-label saxagliptin 5 mg and metformin for 8 weeks. Following the end of the open-label period, patients with inadequate glycaemic control (HbA1c 7%–10.5%) were randomised to receive either placebo or dapagliflozin 10 mg in addition to open-label saxagliptin and metformin.

Data further detailing this lead-in period was accepted as a late-breaker poster (#133-LB) on display in Poster Hall B on Sunday, June 7 from noon to 2 p.m. EST.2

AstraZeneca has filed a New Drug Application (NDA) with the US Food and Drug Administration (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.