Bristol-Myers Squibb has announced that results from a 12-week, Phase IIb dose-ranging study showed that dapagliflozin, a selective, sodium glucose co-transporter2 inhibitor, produced clinically meaningful reductions across all key glycemic measures studied in treatment-naive type 2 diabetes patients, compared to placebo.
The study findings also showed that patients receiving dapagliflozin experienced greater reductions in body weight compared to patients on placebo, the company said.
The Phase IIb study was designed to assess the efficacy and safety of dapagliflozin across a range of doses. The data represent findings from a prospective, randomized, double-blind, placebo-controlled, parallel-group study of 389 individuals with type 2 diabetes (ages 18-79) who were treatment-naive and whose glycosylated hemoglobin level (HbA1c) was greater than or equal to 7% and less than or equal to 10%.
After a two-week lead-in phase that included diet, exercise and placebo, individuals were randomized to one of seven separate treatment arms: dapagliflozin 2.5mg (n=59), 5mg (n=58), 10mg (n=47), 20mg (n=59), 50mg (n=56), metformin extended release 750mg force-titrated at week two to 1,500 mg (n=56) or placebo (n=54), once daily for 12 weeks. Metformin was included as a positive control benchmark; no statistical comparison was made to the metformin arm.
After 12 weeks, individuals receiving dapagliflozin demonstrated a significant adjusted mean decrease in HbA1c from baseline of -0.71% for dapagliflozin 2.5mg, -0.72% for dapagliflozin 5mg, -0.85% for dapagliflozin 10mg, -0.55% for dapagliflozin 20mg and -0.90% for dapagliflozin 50mg, compared to -0.18% for placebo (p-value at the 2.5, 5, 10 and 50mg dose levels less than 0.001; p-value at the 20mg dose level equal to 0.007). The adjusted mean decrease for metformin was -0.73%. No log-linear dose response relationship was demonstrated (P trend=0.41).
Dapagliflozin also demonstrated a clinically meaningful adjusted mean decrease in fasting plasma glucose from baseline of -16mg/dl for dapagliflozin 2.5mg, -19mg/dl for dapagliflozin 5mg, -21 mg/dl for dapagliflozin 10mg, -24mg/dl for dapagliflozin 20mg and -31mg/dl for dapagliflozin 50mg, compared to -6mg/dl for placebo (p-value at the 2.5mg dose level equal to 0.03; p-value at the 5mg dose level equal to 0.005; p-value at the 10mg dose level equal to 0.002; p-value at the 20mg and 50mg dose levels less than or equal to 0.001). The adjusted mean decrease for metformin was -18mg/dl.
The percentage of individuals treated with dapagliflozin that achieved HbA1c of less than 7% after the 12-week treatment period was 46% for dapagliflozin 2.5mg, 40% for dapagliflozin 5mg, 52% for dapagliflozin 10mg, 46% for dapagliflozin 20mg and 59% for dapagliflozin 50mg, compared to 32% for placebo and 54% for metformin. The 50mg result was the only statistically significant result, with a p-value equal to 0.01.
The rate of reported hypoglycemic events was 7% for dapagliflozin 2.5mg, 10% for dapagliflozin 5mg, 6% for dapagliflozin 10mg, 7% for dapagliflozin 20mg and 7% for dapagliflozin 50mg; the incidence of reported hypoglycemic events was 4% for placebo and 9% for metformin. There was no occurrence of confirmed hypoglycemia.
The Phase IIb study also evaluated the potential impact of dapagliflozin-induced glucosuria on weight loss in people with type 2 diabetes, compared to placebo. These findings included data measuring changes in total body weight and body mass index over the 12-week study period.
Overall, greater percent decreases in total body weight occurred in the dapagliflozin treatment groups: -2.7% for dapagliflozin 2.5mg, -2.5% for dapagliflozin 5mg, -2.7% for dapagliflozin 10mg, -3.4% for dapagliflozin 20mg and -3.4% for dapagliflozin 50mg compared to -1.2% for placebo and -1.7% for metformin, the company noted.