NEW YORK (Reuters Health) – A novel glucose-lowering drug, dapagliflozin, improves glycemic control in patients with type 2 diabetes already on metformin, and it promotes significant weight loss, according to the results of a trial reported in Diabetes Care online August 4.

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

Dr. Michael A. Nauck, with the Diabetes Centre in Bad Lauterberg, Germany, and colleagues explain that dapagliflozin is a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor. This class of agents reduces glucose reabsorption from the proximal tubule of the kidney, leading to increased urinary glucose excretion and net caloric loss.

Dapagliflozin has been shown to be effective as monotherapy and as adjunctive therapy for type 2 diabetes in trials lasting 24 weeks. The current 52-week study compared dapagliflozin against the sulfonylurea glipizide as add-on therapy in 814 patients with type 2 diabetes inadequately controlled on metformin.

Mean baseline HbA1c was 7.7%. This 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.

Other, secondary endpoints were significantly different. The mean adjusted weight change was a drop of 3.2 kg with dapagliflozin compared to a gain of 1.2 kg with glipizide. Also, at least one episode of hypoglycemia was documented in 3.5% of the dapagliflozin patients versus 40.8% of the glipizide group.

Adverse events were similar in both groups, the authors report. 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. They say this should be evaluated further in long-term studies of selective SGLT2 inhibitors.

Meanwhile, they conclude, “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.”

Reference:
Dapagliflozin Versus Glipizide as Add-on Therapy in Patients With Type 2 Diabetes Who Have Inadequate Glycemic Control With Metformin
Diabetes Care 2011.