In adult patients with type 2 diabetes mellitus who are uncontrolled on metformin and sulfonylurea, dapagliflozin can be added to help improve HbA1c and reduce fasting plasma glucose, body weight, and seated systolic blood pressure, according to results from a study presented at the 49th Annual Meeting of the European Association for the Study of Diabetes in Barcelona, Spain, in September.
In adult patients with type 2 diabetes mellitus (T2DM) who are uncontrolled on metformin and sulfonylurea, dapagliflozin can be added to help improve HbA1c and reduce fasting plasma glucose, body weight, and seated systolic blood pressure, according to results from a study presented at the 49th Annual Meeting of the European Association for the Study of Diabetes (EASD) in Barcelona, Spain, in September.
The randomized, double-blind phase 3 study, announced by AstraZeneca and Bristol-Myers Squibb, evaluated dapagliflozin in 216 adult patients with T2DM who were inadequately controlled on combination treatment with metformin plus sulfonylurea.
Patients treated with dapagliflozin 10 mg as an add-on therapy to metformin plus sulfonylurea demonstrated significant improvements in HbA1c and, among key secondary end points, significant reductions in fasting plasma glucose (FPG) and in body weight compared to placebo at 24 weeks. Significant improvements were also observed in seated systolic blood pressure (SBP) at 8 weeks in patients treated with dapagliflozin compared to placebo. A 28-week extension of the study is currently ongoing.
“Additionally, dapagliflozin was well tolerated,” according to Stephen Matthaei, MD, primary study inverstigator and director of the Diabetes and Metabolism Center, Quakenbrück Hospital, Quakenbrück, Germany. “Adverse events were mostly mild or moderate, and there were similar rates of events between patients who were treated with dapagliflozin and those who received placebo.”
“The results from this study are important to managed care and hospital decision-makers because they show dapagliflozin can be administered to patients who are already receiving two of the most widely used oral antidiabetic therapies but are still uncontrolled,” Dr Matthaei said. “In current clinical practice, we would typically add insulin when a patient remains uncontrolled on metformin and sulfonylurea, although the American Diabetes Association/EASD guidelines note that a DPP-4 inhibitor or GLP-1 agonist can also be used. This trial shows that the addition of the SGLT2 inhibitor dapagliflozin, when used as part of a triple oral therapy regimen with metformin and sulfonylurea, could be another option for these patients.”
In previous clinical trials, dapagliflozin has been shown to be well tolerated and effective in improving glycemic control and promoting weight loss in patients with T2DM both as monotherapy and in combination with metformin, sulfonylurea, or insulin, according to Dr. Matthaei.
“We conducted this study to determine if dapagliflozin, when used as part of a triple oral therapy regimen with metformin and sulfonylurea, would improve glycemic control via its novel insulin-independent mechanism,” he said.
In July, FDA accepted the NDA resubmission of dapagliflozin. In January 2012 FDA had rejected the original NDA, citing the need for additional risk/benefit data.