Dapagliflozin more effective than sitagliptin for adult patients with type 2 diabetes

Bristol-Myers Squibb Company (NYSE: BMY) and AstraZeneca (NYSE: AZN) today announced results from a Phase 3 clinical study that showed the investigational compound dapagliflozin 10 mg demonstrated significant reductions in blood sugar levels (glycosylated hemoglobin levels, or HbA1c) compared with placebo at 24 weeks when either agent was added to existing sitagliptin therapy (with or without metformin) in adult patients with type 2 diabetes. The results were maintained over a 24-week extension and similar results were observed when the data were stratified by background therapy. The findings were presented today at the 72^nd American Diabetes Association (ADA) Scientific Sessions in Philadelphia, PA.

The study also demonstrated significant reductions in total body weight and fasting plasma glucose (FPG) levels in patients taking dapagliflozin added to sitagliptin (with or without metformin), with results maintained throughout the duration of the study extension.

Patients were actively questioned at each study visit for signs, symptoms or events suggestive of genital infections and urinary tract infections. These events were more frequent with the dapagliflozin treatment group compared to the placebo treatment group, and were generally mild to moderate in intensity, with most patients responding to standard treatment.

"Type 2 diabetes is a complex disease that often requires patients to take multiple treatments to control their blood sugar levels, with DPP4 inhibitors being some of the most widely prescribed therapies," said Serge Jabbour, M.D., Division Director of Endocrinology, Thomas Jefferson University. "In this study, dapagliflozin, in addition to diet and exercise, resulted in reduced blood sugar levels when added to sitagliptin, a DPP4 inhibitor. These findings add to our understanding of the effect of dapagliflozin in combination with commonly prescribed type 2 diabetes treatments."

Dapagliflozin, an investigational oral compound, is a selective and reversible inhibitor of sodium-glucose cotransporter 2 (SGLT2), which works independently of insulin. Dapagliflozin is under joint development by Bristol-Myers Squibb and AstraZeneca, and is being investigated to evaluate its safety and efficacy in improving glycemic control in adults with type 2 diabetes as an adjunct to diet and exercise, for once-daily use as a monotherapy and in combination with other glucose-lowering drugs. If approved, dapagliflozin would potentially be the first in the new SGLT2 inhibitor class for the treatment of type 2 diabetes, a disease where high unmet medical need exists. In a comprehensive clinical trial program of 19 studies, dapagliflozin has been studied together with diet and exercise as a monotherapy, and as an add-on therapy to commonly prescribed diabetes medications, including metformin, sulfonylurea (glimepiride), thiazolidinedione (pioglitazone), and insulin (with or without other diabetes therapies).

In January 2012, the U.S. Food and Drug Administration (FDA) issued a complete response letter regarding the New Drug Application (NDA) for dapagliflozin for the treatment of adults with type 2 diabetes, requesting additional clinical data to allow a better assessment of the benefit-risk profile for dapagliflozin. In April 2012, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) issued a positive opinion recommending the approval of dapagliflozin for the treatment of type 2 diabetes as an adjunct to diet and exercise, in combination with other glucose-lowering medicinal products including insulin, and as a monotherapy in metformin intolerant patients. The CHMP positive opinion for dapagliflozin will now be reviewed by the European Commission, which has the authority to approve medicines for the European Union.