Adding dapagliflozin to metformin as a treatment for type 2 diabetes patients who cannot reach adequate glucose control can improve glucose control and lower body weight without risk of hyperglycemia, according to trial results, presented at the annual conference of the American Diabetes Association (ADA) in Orlando, Fla., and published in the June 24 edition of the Lancet.
While metformin is generally the best first-line approach to controlling glucose, additional therapy is often required. Dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, has the potential to reduce renal glucose reabsorption in diabetics with inadequate glucose control.
Clifford J. Bailey, PhD, from Aston University in Birmingham, England, and colleagues measured the safety and efficacy of a dapagliflozin treatment for type 2 diabetes patients who did not have ample glucose control with a treatment of metformin.
The trial, which took place between Sept. 18, 2007, and April 10, 2008, enrolled 546 patients with type 2 diabetes who were administered metformin at least eight weeks prior to study enrollment.
Patients received three doses of dapagliflozin: 137 patients received 2.5 mg of the drug, 137 received 5 mg, 135 received 10 mg, while 137 patients received placebo.
Researchers used a patient’s change in baseline in hemoglobin A1c as the primary outcome and evaluated patients for 24 weeks.
After the 24 weeks, researchers found that the mean change in baseline for the four aforementioned groups was -0.67, -0.70, -0.84 and -0.30 percent, respectively.
More patients in the control group achieved a better HbA1c response of 7 percent or less, compared to the placebo group, 40 percent versus 25.9 percent, respectively.
Patients who presented to the study with HbA1c rates of 9 percent or higher had greater reductions in HbA1c levels compared to those in the placebo group. These rates decreased by 0.85 percent for patients administered 5 mg of dapagliflozin and 0.78 percent for those administered a 10 mg dose.
Additionally, results showed that body weight had dropped in patients administered dapagloflozin compared to those who received placebo, 18.1 percent administered a 2.5 mg dose, 19.5 percent (5 mg) and 22.1 percent (10 mg) lost 5 percent of more of body weight.
Results showed that patients experienced 17 events including rotator cuff syndrome, chest pain, atrial fibrillation and MI, among others. Four of these events happened in the 2.5 mg group, four in the 5 mg arm, four in the 10 mg and five in placebo.
“Dapagliflozin offers a novel insulin-independent approach to lowering hyperglycemia and improving metabolic control of type 2 diabetes: It reduces renal glucose reabsorption by inhibition of SGLT2 transporters in the proximal tubule of the kidney, resulting in urinary glucose excretion,” the authors wrote.
Additionally, the authors wrote that dapagliflozin was able to act independently of insulin, was not associated with hyperglycemia and was able to reduce overall body weight in patients. “Therefore, addition of dapagliflozin to metformin provides a new therapeutic option for treatment of type 2 diabetes,” the authors concluded.
The phase III study was funded by Bristol-Myers Squibb and AstraZeneca.