Add-on Dapagliflozin Improves Diabetes Control without Weight Gain

The investigational glucose-lowering drug dapagliflozin improved glycemic control in patients with type 2 diabetes already on metformin, and it promoted significant weight loss, in a phase II trial.…

“Dapagliflozin is a potential valuable alternative to sulfonylureas as add-on therapy when metformin monotherapy fails to maintain adequate glycemic control,” the authors conclude.

Adverse events were no more common with dapagliflozin, the authors report. That was not the case in later studies, however, and last month a U.S. federal advisory committee declined to recommend approval of dapagliflozin because of safety concerns, including a possible increased risk of breast and bladder cancers. A final decision by the U.S. Food and Drug Administration is expected in late October.

Dapagliflozin, a selective sodium-glucose cotransporter 2 inhibitor, reduces glucose resorption from the proximal tubule of the kidney, leading to increased urinary glucose excretion and net caloric loss.

The authors of the current paper, led by Dr. Michael A. Nauck, with the Diabetes Centre in Bad Lauterberg, Germany, compared dapagliflozin to the sulfonylurea glipizide as add-on therapy in 814 patients with type 2 diabetes inadequately controlled on metformin.

Patients took the assigned treatment for a year. Mean HbA1c — 7.7% at baseline — fell more rapidly at first in the glipizide group but then rose, while the dapagliflozin group showed a steadier drop. The result was an identical decrease in HbA1c of 0.52% in both groups at 52 weeks.

Secondary endpoints were significantly different, however. The mean adjusted weight dropped by 3.2 kg with dapagliflozin but increased by 1.2 kg with glipizide. Also, the proportion of patients with at least one episode of hypoglycemia was 40.8% with glipizide but only 3.5% with dapagliflozin.

Serious adverse events related to treatment occurred in six patients on dapagliflozin and in four on glipizide.

“Higher proportions of patients receiving dapagliflozin reported events suggestive of genital infections or lower UTIs compared with glipizide,” Dr. Nauck and colleagues report.

“This head-to-head comparison of dapagliflozin versus glipizide added to metformin in type 2 diabetic patients poorly controlled with metformin monotherapy demonstrated similar glycemic efficacy at 52 weeks but markedly divergent effects on weight and hypoglycemia,” the research team concluded.

Diabetes Care August 4, 2011