Phase III combination trial of Bydureon and Forxiga shows significant benefits in patients with type-2 diabetes

DURATION-8 trial met primary and secondary endpoints, significantly reducing blood
sugar (HbA1c), weight and systolic blood pressure versus either medicine alone

The first trial to assess GLP-1RA/SGLT-2i combination therapy

16 September 2016

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.¹

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% (-2.5 kg)
• Significantly greater systolic blood pressure reduction (–4.2 mmHg vs –1.3 mmHg and –1.8 mmHg, respectively; both P<0.05)¹

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.¹

NOTES TO EDITORS

About DURATION-8
DURATION-8 was a phase III, randomised, multicentre, double-blind, active controlled trial which evaluated the safety and efficacy of simultaneous administration of exenatide once weekly and dapagliflozin once daily compared to treatment with the individual medicines in adult patients with type-2 diabetes who were inadequately controlled on metformin.¹

The trial was conducted over a 28-week treatment period, with an extension to two years, and enrolled approximately 700 patients in six countries. Eligible participants included adult patients with type-2 diabetes who had uncontrolled HbA1c (a protein within red blood cells that when bound with glucose is measurable to determine average blood sugar levels during a specific period) levels at baseline ranging from 8.0% to 12.0%. The primary endpoint was change in HbA1c from baseline to week 28. Secondary endpoints included changes in body weight, systolic blood pressure, fasting plasma glucose, two-hour postprandial glucose and the proportion of patients achieving HbA1c <7.0% over the 28-week treatment period.¹

About AstraZeneca in Diabetes
AstraZeneca is pushing the boundaries of science with the goal of developing life-changing medicines that aim to reduce the global burden and complications of diabetes. As a core therapy area for the company, we are focusing our research and development efforts on diverse populations and patients with significant co-morbidities, such as cardiovascular disease, obesity, non-alcoholic steatohepatitis (NASH), and chronic kidney disease.

Our commitment to diabetes is exemplified by the depth and breadth of our global clinical research programme. This commitment is advancing understanding of the treatment effects of our diabetes medicines in broad patient populations, as well as exploring combination product approaches to help more patients achieve treatment success earlier in their disease progression. Our ambition is to reduce the long-term impact of diabetes.

About AstraZeneca
AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of diseases in three therapy areas – Respiratory and Autoimmunity, Cardiovascular and Metabolic Diseases, and Oncology. The company is also active in inflammation, infection and neuroscience through numerous collaborations. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information, please visit: www.astrazeneca.com

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References

1. Guja C., et al. Combination of once weekly injection of exenatide and once daily oral dapagliflozin: Results of the DURATION-8 Clinical Trial. Lancet Diabetes & Endocrinology. 16 September 2016. http://dx.doi.org/10.1016/S2213-8587(16)30263-7.
2. International Diabetes Federation. IDF Diabetes Atlas, 7th ed. Brussels, Belgium: International Diabetes Federation, 2015.