Dapagliflozin, metformin XR, or both: initial pharmacotherapy for type 2 diabetes, a randomised controlled trial
International Journal of Clinical Practice, 04/23/2012
Henry RR et al. - In treatment-naïve patients with type 2 diabetes (T2D), dapagliflozin plus metformin was generally well tolerated and effective in reducing HbA1c, fasting plasma glucose (FPG) and weight. Dapagliflozin-induced glucosuria led to an increase in events suggestive of urinary tract and genital infections.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 5mg (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.
- 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.