More Information Showing Dapagliflozin Improves Glycemic Control

John R. White, PA, PharmD, a professor of pharmacotherapy at Washington State University in Spokane, Wash., and colleagues analyzed data from three phase-3 randomized  controlled clinical trials that assessed the efficacy and safety of dapagliflozin in more than 1,500 patients at multiple sites worldwide who had type 2 diabetes and inadequate glycemic control from diet and exercise alone.

"Dapagliflozin significantly reduced HbA1c in a dose-dependent manner in all studies," the researchers wrote.

The first study (NCT00528372) assessed dapagliflozin as monotherapy in patients who had not been previously treated. The second study (NCT00680745) assessed the safety and efficacy of dapagliflozin as an add-on therapy administered with glimepiride, and the third trial (NCT00528879) assessed dapagliflozin in combination with metformin. Study participants in all three trials were assigned to one of three dapagliflozin doses (2.5 mg once daily, 5 mg once daily or 10 mg once daily for 24 weeks) or placebo.

Patients in all three studies met primary endpoints for reductions in baseline Hba1C as follows:

• Study one: placebo subtracted mean changes in Hba1c were -0.35 in 2.5 mg dapagliflozin group; -0.54 in the 5 mg group and -0.66 in the 10 mg group.
• Study two: -0.44 in the 2.5 mg dapagliflozin group; -0.49 in the 5 mg group and -0.68 in the 10 mg group.
• Study three: -0.38 in the 2.5 mg dapagliflozin group; -0.41 in the 5 mg group and -0.54 in the 10 mg group.

Patients assigned to dapagliflozin as add-on therapy with either glimepiride and metformin also met secondary endpoints for statistically significant weight loss, with placebo-subtracted mean changes in baseline ranging from -0.8 to -1.5 kg among patients that received either 5 mg or 10 mg doses of dapagliflozin with glimepiride, and -1.3 to -2.2 kg among patients that received any dose of dapagliflozin with metformin.

Across all studies, patients assigned to dapagliflozin experienced mean absolute decreases in seated systolic BP ranging from -2.1 to -5.2 mm Hg vs. -0.2 to -1.6 mm Hg in placebo groups.

Rates of hypoglycemic events, adverse events and study discontinuations were similar across all treatment groups. "There were increased reports of signs, symptoms and events suggestive of genital infection in all dapagliflozin groups in all three studies and of urinary tract infections in dapagliflozin groups in study one," the researchers wrote. "There were, however, no treatment-related discontinuations for genital and urinary tract infections."

Presented at 39^th American Academy of Physician Assistants Annual Meeting 2011