Positive results from the Phase III DURATION-8 trial demonstrated that Bydureon (exenatide extended-release formulation) 2mg once weekly in combination with Forxiga (dapagliflozin) 10mg once daily significantly reduced blood sugar as measured by HbA1c, versus the individual medicines alone in patients with type-2 diabetes inadequately controlled on metformin.
This was the first clinical trial to combine these two different anti-diabetes medicines, a GLP-1 receptor agonist and an SGLT-2 inhibitor, as an addition to standard-of-care therapy to evaluate potential benefits for patients with type-2 diabetes with inadequate glycaemic control. The results were presented today at the 52nd Annual Meeting of the European Association for the Study of Diabetes (EASD) in Munich, Germany, and simultaneously published in The Lancet Diabetes & Endocrinology.1
The trial achieved its primary endpoint with the combination of exenatide and dapagliflozin significantly reducing HbA1c from baseline compared with exenatide or dapagliflozin alone (1.95% versus 1.58% and 1.37% respectively, both P<0.01)1 at 28 weeks. It also confirmed the robust efficacy of dapagliflozin in patients not reaching their treatment goal with metformin.
Serge A. Jabbour, MD, FACP, FACE, Professor of Medicine, Director of the Division of Endocrinology and Director of the Diabetes Center at the Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, said: “Because of the progressive nature of type-2 diabetes, patients often require multiple antidiabetic medicines to achieve and maintain glycaemic control. The results of DURATION-8 show that combining medicines that work in different ways can significantly reduce HbA1c, as well as weight and systolic blood pressure.”
Elisabeth Björk, Vice President, Head of Cardiovascular and Metabolic Diseases, Global Medicines Development at AstraZeneca, said: “With DURATION-8, AstraZeneca is the first company to highlight the potential benefits of combining a GLP-1 receptor agonist and SGLT-2 inhibitor as a highly-effective treatment alternative to existing non-insulin therapies for patients with severe, uncontrolled type-2 diabetes. Further, it reinforces our commitment to pushing the boundaries of science in the treatment of a disease that affects an estimated 415 million adults worldwide.2”
Secondary endpoints for the trial included changes in body weight and systolic blood pressure. Patients receiving the combination of exenatide and dapagliflozin versus either exenatide or dapagliflozin alone experienced:
• Significantly greater body weight reduction (–3.4 kg versus –1.5 kg and –2.2 kg, respectively; both P<0.01); weight reductions seen with the combination were greater (–4.5 kg) in patients with a baseline HbA1c of 8.0-9.0% versus those with a baseline greater than 9.0% (–2.6 kg)
• Significantly greater systolic blood pressure reduction (–4.2 mmHg vs –1.3 mmHg and –1.8 mmHg, respectively; both P<0.05)
The combination of exenatide and dapagliflozin exhibited similar rates of adverse events and serious adverse events to the individual medicine treatment groups. The most common adverse events (≥ 5% of patients in any group) were diarrhoea, injection-site nodules, nausea and urinary tract infections.
Filed Under: Drug Discovery
