Bristol-Myers Squibb and AstraZeneca announced results from their Phase 3 trial of dapagliflozin (as monotherapy) for treatment-naïve adults with type 2 diabetes. This study included 485 individuals (ages 18 – 77) who had a HbA1c level between 7.0 and 10.0% and were unable to control glycemic levels with diet and exercise alone. The primary endpoint was mean change from baseline at week 24 in HbA1c in the main cohort. Key secondary efficacy measures included change from baseline at week 24 in FPG and body weight.
After 24 weeks, individuals in the main cohort receiving dapagliflozin 5 mg and 10 mg demonstrated a statistically significant adjusted mean change in HbA1c from baseline of -0.77% and -0.89% respectively, compared to -0.23% for placebo (p-value less than 0.001 and p-value less than 0.0001 respectively, versus placebo). Individuals receiving dapagliflozin 2.5 mg experienced an adjusted mean change in HbA1c of -0.58% (p-value of 0.02). Individuals treated with dapagliflozin 5 mg and 10 mg demonstrated statistically significant reductions in FPG, a secondary endpoint, at week 24 from baseline: -24.1 mg/dL for dapagliflozin 5 mg and -28.8 mg/dL for dapagliflozin 10 mg, compared to -4.1 mg/dL for placebo (p-value 0.0007 and p-value less than 0.0001 respectively, versus placebo). Individuals receiving dapagliflozin 2.5 mg experienced a reduction of -15.2 mg/dL. Additionally, at week 24, the decrease in adjusted mean total body weight, a secondary endpoint, was greater with each dapagliflozin dose compared to placebo, although not reaching statistical significance (-3.3 kg, -2.8 kg, -3.2 kg with dapagliflozin 2.5 mg, 5 mg and 10 mg respectively, versus -2.2 kg with placebo).
Dapagliflozin is a potential first-in-class sodium-glucose cotransporter-2 (SGLT2) inhibitor. The protein SGLT2 is responsible for the majority of glucose reabsorption and helps the body retain glucose for its energy requirements. In patients with diabetes, retention of excess glucose by this pathway contributes to persistent hyperglycemia.