Date: 2014-05-13
Type of information:
phase: 3
Announcement: results
Company: AstraZeneca (UK)
Product: saxagliptin/dapagliflozin combination
Action
mechanism: Saxagliptin (marketed as Onglyza®) belongs to the class of medicines called DPP-4 inhibitors, which work by increasing the activity of the incretin hormones, increasing the release of insulin when glucose levels are elevated and reducing the levels of sugar produced by the liver (glucagon). Dapagliflozin (marketed as Farxiga™ in the U.S. and Forxiga® outside the U.S.) is part of a newer class of medicines called sodium-glucose cotransporter 2 (SGLT2) inhibitors, which remove glucose via the kidneys.
Disease: type 2 diabetes
Therapeutic area: Metabolic diseases
Country:
Trial
details: This 24-week, Phase III, multi-center, 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%). The study included 534 adult patients with type 2 diabetes (aged ≥ 18 years) with inadequate glycaemic control (HbA1c ≥ 8% and ≤ 12%) 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.
Latest
news: * On May 13, 2014, AstraZeneca announced positive results from Phase III study of saxagliptin/dapagliflozin combination in patients with type 2 diabetes 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% in the saxagliptin/dapagliflozin combination group compared to -0.88% in the saxagliptin group and -1.20% in the dapagliflozin group. More patients in the saxagliptin/dapagliflozin combination group (41%) achieved goal HbA1c levels of less than 7% compared to patients in the saxagliptin (18%) and dapagliflozin (22%) groups.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.AstraZeneca will commence a Phase III trial for dapagliflozin in patients with Type 1 diabetes in 2014.
