Phase 3 study of dapagliflozin in combination with metformin for type 2 diabetes

Bristol-Myers Squibb and AstraZeneca announced positive results from a Phase 3 study of dapagliflozin as add-on therapy to metformin for the treatment of type 2 diabetes. This 24-week, randomized, double-blind, placebo-controlled study was designed to assess the efficacy and safety of dapagliflozin as an add-on to metformin in 546 patients with inadequately controlled type 2 diabetes whose A1C was ≥7% and ≤10% at baseline. Patients were randomized to receive dapagliflozin 2.5mg, 5mg, or 10mg, or placebo in addition to metformin 1500mg/day or greater.

After 24 weeks, individuals receiving dapagliflozin 2.5 mg, 5 mg and 10 mg plus metformin demonstrated a statistically significant adjusted mean change in HbA1c from baseline of -0.67 percent, -0.70 percent and -0.84 percent, respectively, compared to -0.30 percent for placebo. Individuals treated with dapagliflozin demonstrated a statistically significant adjusted mean change in FPG, a secondary endpoint, from baseline at Week 24: -17.8 mg/dL for dapagliflozin 2.5 mg -21.5 mg/dL for dapagliflozin 5 mg and -23.5 mg/dL /dl for dapagliflozin 10 mg, compared to -6.0 mg/dL for placebo.

The adjusted percentage of individuals treated with dapagliflozin who achieved HbA1c of less than 7 percent at 24 weeks, a secondary endpoint, was 33% for dapagliflozin 2.5 mg, not significant, 37.5% for dapagliflozin 5 mg, and 40.6% for dapagliflozin 10 mg statistically significant compared to 25.9% for placebo.

The study also evaluated the potential impact of dapagliflozin on weight loss. These findings included data measuring changes in total body weight over the 24-week study period. At 24 weeks, the change in total body weight in kg, a secondary endpoint, was -2.21 kg for dapagliflozin 2.5 mg, -3.04 kg for dapagliflozin 5 mg and -2.86 kg for dapagliflozin 10 mg, compared to -0.89 kg for placebo.

Dapagliflozin is a novel, selective, sodium glucose co-transporter 2 (SGLT2) inhibitor, currently being evaluated in Phase 3 trials as a once-daily oral therapy for the treatment of type 2 diabetes. SGLT2 inhibitors facilitate the elimination of glucose by the kidney, thereby returning serum glucose levels towards normal.

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