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news.Demonstrated improved glycemic control, and weight reduction in Type 2 Diabetes
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Bristol-Myers Squibb and AstraZeneca have announced the results from a 24-week phase 3 clinical study, which demonstrated that dapagliflozin, added to metformin, showed significant mean reductions in the primary endpoint, glycosylated hemoglobin level (HbA1c) and in the secondary endpoint, fasting plasma glucose (FPG) in patients with type 2 diabetes inadequately controlled with metformin alone, as compared to placebo plus metformin.
The study was designed to assess the efficacy and safety of dapagliflozin as an add-on to metformin over 24 weeks in patients with inadequately controlled type 2 diabetes. The data represent findings from a randomised, double-blind, placebo-controlled study of 546 individuals with type 2 diabetes (ages 18 –77) whose HbA1c was greater than or equal to 7.0% and less than or equal to 10% at baseline.
After a two-week lead-in phase, individuals were randomised to one of four separate treatment arms: dapagliflozin 2.5mg (n= 137), dapagliflozin 5mg (n= 137), dapagliflozin 10mg (n= 135), or placebo (n= 137). Patients in all arms also received metformin (greater than or equal to 1500mg/d). The primary endpoint of the study compared mean HbA1c change from baseline for each dapagliflozin treatment arm compared to placebo after 24 weeks.
Secondary endpoints included change from baseline in FPG and body weight at week 24 as compared to placebo, and adjusted percentage of individuals treated with dapagliflozin who achieved HbA1c of less than 7% at 24 weeks. Exploratory endpoints included body weight decrease of greater than or equal to 5% or greater than or equal to 10% as well as body weight percent change from baseline. The study includes an extension phase for a total duration of two years.
After 24 weeks, individuals receiving dapagliflozin 2.5mg, 5mg and 10mg plus metformin demonstrated a statistically significant adjusted mean change in HbA1c from baseline of -0.67%, -0.70% and -0.84%, respectively, compared to -0.30% 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 2.5mg -21.5mg/dl for dapagliflozin 5mg and -23.5mg/dl /dl for dapagliflozin 10mg, compared to -6.0mg/dl for placebo.
The adjusted percentage of individuals treated with dapagliflozin who achieved HbA1c of less than 7% at 24 weeks, a secondary endpoint, was 33.0% for dapagliflozin 2.5mg, not significant (p-value 0.1775), 37.5% for dapagliflozin 5mg, and 40.6% for dapagliflozin 10mg 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 -2.21kg for dapagliflozin 2.5mg, -3.04kg for dapagliflozin 5mg and -2.86kg for dapagliflozin 10mg, compared to -0.89kg for placebo. Overall, more patients taking dapagliflozin achieved weight losses greater than or equal to 5% compared to placebo, an exploratory endpoint (24% for dapagliflozin 2.5mg, 25.4% for dapagliflozin 5mg, 28.0% for dapagliflozin 10mg, compared to 5.9% for placebo).