British biopharmaceutical company AstraZeneca recently announced positive results from a Phase III study led by a Dallas-based researcher that measured the effect of combining saxagliption (an oral anti-diabetic drug) and dapagliflozin (also a drug for the treatment of diabetes) as a dual add-on therapy in adult patients with type 2 diabetes, who were previously inadequately controlled on metformin.
AstraZeneca, who has been making headlines since Pfizer announced its intention to buy the biopharmaceutical company, was this year’s winner of Bio-It World’ Best Practices Awards, in the category of Clinical & Health, for their Real Time Analytics for Clinical Trials (REACT).
The company is now making it into the news again, as it concludes that diabetic patients who were treated with this combination, plus metformin (an oral anti diabetic drug in the biguanide class), significantly reduced their glycated hemoglobin (HbA1c) levels, when compared to using the agent alone plus metformin at 24 weeks of treatment. The change from original HbA1c levels was of -1.47% in the saxagliptin/dapagliflozin combination group, compared to -0.88% in the saxagliptin alone group and -1.20% in the dapagliflozin alone group.
Specifically, 41% of the patients in the saxagliptin/dapagliflozin combination group achieved goal HbA1c levels of less than 7%, whereas only 18% of the patients in the saxagliptin and 22% in the dapagliflozin groups achieved the goal.
A progressive disease in which nearly half of patients can’t achieve their HbA1c goals, diabetes requires “new and earlier therapeutic approaches that provide more robust HbA1c lowering,” said Dr. Julio Rosenstock, the study’s lead investigator, director of the Dallas Diabetes and Endocrine Center at Medical City and a clinical professor at the University of Texas Southwestern Medical School.
According to Dr. Rosenstock, the research team noticed that when saxagliptin and dapagliflozin are combined, patients who were not adequately treated with metformin alone achieve significant weight loss, which ultimately reduces HbA1c. In addition, patients achieved the HbA1c goal without increasing the risk of hypoglycemia.
The Phase III trial was conducted through 24 weeks as a multi-center, randomized, double-blind, active-controlled, parallel-group study. The primary endpoint was mean change in HbA1c from original levels to the final week. Secondary endpoints included mean change from baseline in two-hour postprandial blood glucose test during a liquid meal test, fasting plasma glucose, body weight at week 24 in the saxagliptin/dapagliflozin combination group versus the saxagliptin group, and the proportion of patients who achieved glycemic response (defined as HbA1c < 7%).
The study included 534 over-18 years old patients with type 2 diabetes with inadequate glycemic control who were receiving metformin extended-release (≥ 1,500 mg per day). Patients were randomized 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.