AstraZeneca announced results from a phase III study evaluating the investigational combination of saxagliptin/dapagliflozin as a dual add-on therapy in adult patients with type 2 diabetes who were inadequately controlled on metformin.
Results from the combination study found that patients treated with saxagliptin/dapagliflozin plus metformin achieved significantly greater reductions in HbA1c versus either agent alone plus metformin at 24 weeks, with an adjusted mean change from baseline HbA1c of -1.47 per cent in the saxagliptin/dapagliflozin combination group compared to -0.88 per cent in the saxagliptin group and -1.20 per cent in the dapagliflozin group. More patients in the saxagliptin/dapagliflozin combination group (41 per cent) achieved goal HbA1c levels of less than 7 per cent compared to patients in the saxagliptin (18 per cent) and dapagliflozin (22 per cent ) groups.1
The saxagliptin/dapagliflozin combination group achieved a significantly greater adjusted mean reduction from baseline in two-hour postprandial glucose (PPG) versus the saxagliptin group, but not the dapagliflozin group. The adjusted mean reduction in fasting plasma glucose (FPG) was greater in the saxagliptin/dapagliflozin combination group (-38 mg/dL) than the saxagliptin group (-14 mg/dL), but similar to the dapagliflozin group (-32 mg/dL). In this study, overall rates of adverse events, including hypoglycaemia, were similar between the three treatment groups, and most were reported as mild or moderate in intensity.
“Diabetes is a progressive disease in which nearly half of patients do not achieve their HbA1c goals. Despite the standard sequential use of existing therapies, there is a need for new and earlier therapeutic approaches that provide more robust HbA1c lowering,” said lead investigator Julio Rosenstock, managing director, director of the Dallas Diabetes and Endocrine Centre at Medical City and clinical professor of medicine at the University of Texas Southwestern Medical School, Dallas, Texas. “What we’ve observed in this trial is when the two independent mechanisms of action of saxagliptin and dapagliflozin are used in combination, significant reductions in HbA1c associated with weight loss are achieved in patients not adequately treated with metformin alone, and more patients reached the HbA1c target goal without increased risk of hypoglycaemcia while maintaining a similar safety profile to the individual monotherapies.”
“The results for the combination of saxagliptin and dapagliflozin demonstrate our continued commitment to meeting the needs of patients with type 2 diabetes by working to understand how these two medicines with independent mechanisms of action may be used together to help more patients achieve their treatment goals,” said Briggs Morrison, executive vice president, global medicines development & chief medical officer, AstraZeneca.
This 24-week, Phase III, multi-centre, randomised, double-blind, active-controlled, parallel-group trial was designed to evaluate the efficacy and safety of the combination of saxagliptin/dapagliflozin as dual add-on therapy in adult patients with type 2 diabetes with inadequate glycaemic control on metformin. The primary endpoint was mean change in HbA1c from baseline to week 24. Secondary endpoints included mean change from baseline in two-hour PPG during a liquid meal test, FPG, body weight at week 24 in the saxagliptin/dapagliflozin combination group versus the saxagliptin group, and the proportion of patients who achieved glycaemic response (defined as HbA1c < 7 per cent )
The study included 534 adult patients with type 2 diabetes (aged = 18 years) with inadequate glycaemic control (HbA1c = 8 per cent and = 12 per cent ) who were receiving metformin extended-release (= 1,500 mg per day). Patients were randomised 1:1:1 to receive the combination of saxagliptin 5 mg and dapagliflozin 10 mg added to metformin, saxagliptin and metformin added to placebo, or dapagliflozin and metformin added to placebo, for 24 weeks.
Type 1 diabetes patients are dependent on lifelong insulin injections which present a constant risk for hypoglycaemic events and long term weight gain. AstraZeneca will commence a Phase III trial for dapagliflozin in patients with Type 1 diabetes in 2014.