Background: Combining metformin (XR) with dapagliflozin to initiate pharmacotherapy in patients with type 2 diabetes (T2D) and high baseline HbA1c may be advantageous. We conducted two randomised, double-blind, three-arm 24-week trials in treatment-naïve patients to compare dapagliflozin plus metformin, dapagliflozin alone and metformin alone.
Methods: Eligible patients had baseline HbA1c 7.5-12%. Each trial had three arms: dapagliflozin plus metformin, dapagliflozin monotherapy and metformin monotherapy. Dapagliflozin in combination and as monotherapy was dosed at 5 mg (Study 1) and 10 mg (Study 2). Metformin in combination and as monotherapy was titrated to 2000 mg. The primary endpoint was HbA1c change from baseline; secondary endpoints included change in fasting plasma glucose (FPG) and weight.
Results: In both trials, combination therapy led to significantly greater reductions in HbA1c compared with either monotherapy: -2.05 for dapagliflozin + metformin, -1.19 for dapagliflozin, and -1.35 for metformin (p < 0.0001) (Study 1); -1.98 for dapagliflozin + metformin, -1.45 for dapagliflozin and -1.44 for metformin (p < 0.0001) (Study 2). Combination therapy was statistically superior to monotherapy in reduction of FPG (p < 0.0001 for both studies); combination therapy was more effective than metformin for weight reduction (p < 0.0001). Dapagliflozin 10 mg was non-inferior to metformin in reducing HbA1c (Study 2). Events suggestive of genital infection were reported in 6.7%, 6.9% and 2.0% (Study 1) and 8.5%, 12.8% and 2.4% (Study 2) of patients in combination, dapagliflozin and metformin groups; events suggestive of urinary tract infection were reported in 7.7%, 7.9% and 7.5% (Study 1) and 7.6%, 11.0% and 4.3% (Study 2) of patients in the respective groups. No major hypoglycaemia was reported.
Conclusion: In treatment-naïve patients with T2D, dapagliflozin plus metformin was generally well tolerated and effective in reducing HbA1c, FPG and weight. Dapagliflozin-induced glucosuria led to an increase in events suggestive of urinary tract and genital infections.
© 2012 Blackwell Publishing Ltd.