Forxiga dapagliflozin: Phase III data

A double-blind, international Phase III trial in 447 Type II diabetics aged 18 and older who were inadequately controlled with sitagliptin with or without metformin showed that once-daily 10 mg dapagliflozin in combination with sitagliptin with or without metformin met the primary endpoint of reducing HbA1c from baseline to week 24 vs. placebo plus sitagliptin with or without metformin (placebo-adjusted reduction of 0.48%, p<0.0001). On secondary endpoints, dapagliflozin plus sitagliptin with or without metformin led to significant placebo-adjusted reductions from baseline to week 24 in mean FPG (23.3 mg/dL, p<0.0001) and body weight (1.89 kg, p<0.0001). Dapagliflozin did not significantly reduce SBP from baseline to week 24 vs. placebo (5.98 vs. 5.12 mmHg, respectively, p=0.5583).

In the 24-week extension portion of the trial, 18.8% of patients receiving dapagliflozin discontinued treatment or were rescued for failing to achieve glycemic targets vs. 41.5% of patients receiving placebo. At week 48, patients receiving dapagliflozin maintained placebo-adjusted reductions from baseline of 0.68% in HbA1c, 33.1 mg/dL in FPG and 2.22 kg in body weight. The proportion of patients experiencing >=1 adverse event was 66.2% for dapagliflozin vs. 61.1% for placebo. The most common adverse events reported were nasopharyngitis, back pain, urinary tract infection (UTI), pharyngitis, arthralgia and headache. Additionally, >=1 serious adverse event occurred in 6.7% of patients receiving dapagliflozin vs. 8% of patients receiving placebo. Rates of hypoglycemia were 5.3% for dapagliflozin vs. 6.2% for placebo; rates of genital infections were 9.3% and 0.4%; and rates of UTIs were 5.8% and 3.5%. Adverse events suggestive of renal impairment or failure occurred in 8 (3.6%) patients in the dapagliflozin group, including 4 patients with a reduction in renal creatinine clearance rate, vs. 4 (1.8%) patients in the placebo group, including 1 patient with a reduction in renal creatinine clearance rate. Data were presented at the American Diabetes Association meeting in Philadelphia. ...