Phase 3 clinical study demonstrates efficacy of metformin therapy in type 2 diabetes

Sep 24 2010

Bristol-Myers Squibb Company (NYSE: BMY) (http://www.bms.com) and AstraZeneca (NYSE: AZN) (http://www.astrazeneca-us.com) today announced results from a randomized, double-blind Phase 3 clinical study in adults with type 2 diabetes inadequately controlled on metformin therapy alone. The study demonstrated dapagliflozin was non-inferior compared to glipizide (sulphonylurea) in improving glycosylated hemoglobin levels (HbA1c) when added to existing metformin therapy during a 52-week treatment period. The study also demonstrated that dapagliflozin plus metformin achieved significant reductions in key efficacy secondary endpoints: reduction in total body weight from baseline, compared with a weight gain on glipizide plus metformin therapy and a reduced number of patients reporting one or more hypoglycemic events. Treatments were titrated during the first 18 weeks, up to 10 mg/day for dapagliflozin plus metformin (median dose 10 mg/day) or 20 mg/day for glipizide (median dose 20 mg/day). Results from the study were presented at the 46th European Association for the Study of Diabetes (EASD) Annual Meeting.

Overall, the frequencies of adverse events, serious adverse events and study discontinuations were comparable across the two treatment groups; although signs, symptoms and other reports suggestive of urinary tract or genital infections were more common in dapagliflozin treated subjects.

Dapagliflozin, an investigational compound, is a first-in-class sodium-glucose cotransporter-2 (SGLT2) inhibitor and is currently in Phase 3 trials under joint development by Bristol-Myers Squibb and AstraZeneca as a once-daily oral therapy for the treatment of adult patients with type 2 diabetes. SGLT2 inhibitors, which act independently of insulin mechanisms, facilitate the excretion of glucose and associated calories in the urine, thereby lowering blood glucose levels.

"Type 2 diabetes patients often present with multiple co-morbidities in addition to their blood sugar levels," said Michael A. Nauck, MD, Head of Diabetes Center, Bad Lauterberg (Germany), principle investigator of the study. "We are pleased to see the results from this Phase 3 study found that dapagliflozin plus metformin compared favorably to glipizide plus metformin, helping patients lower their HbA1c levels with a lower risk of hypoglycemia."