The efficacy and safety of saxagliptin a potent, selective dipeptidyl peptidase-4 (DPP-4) inhibitor, specifically designed for extended inhibition of the DPP-4 enzyme was investigated in two double-blind, randomised trials (CV181-014/Study 1 and CV181-039/Study 2), either as add-on therapy in patients with type 2 diabetes mellitus (T2DM) inadequately controlled by metformin alone (HbA1c 7.010.0%) or as initial combination therapy with metformin in drug-naïve T2DM patients (HbA1c 8.012.0%), respectively.
Following a placebo run-in, patients with inadequately controlled T2DM (n=743) on metformin, in Study 1, were randomised to receive once-daily saxagliptin 2.5, 5.0 or 10.0 mg, or placebo, plus their stable metformin dose, and drug-naïve patients (n=1306), in Study 2, were randomised to receive saxagliptin/metformin 5/500 mg (S5/MET), 10/500 mg (S10/MET), saxagliptin 10 mg or metformin 500 mg once-daily. In the S5/MET, S10/MET and metformin alone treatment groups of Study 2, metformin was up-titrated incrementally (Weeks 15) to a maximum of 2000 mg/day. Both studies primary endpoint was HbA1c change from baseline. Treatment groups were well balanced for baseline characteristics within each study.
At week 24, significant (P<0.0001) reductions in adjusted-mean HbA1c change from baseline were observed in Study 1 for saxagliptin 2.5, 5.0 and 10.0 mg (−0.59, −0.69 and −0.58%, respectively), compared with placebo (0.13%), and in Study 2 for S5/MET (−2.53%) and S10/MET (−2.49%), compared with saxagliptin (−1.69%) or metformin (−1.99%) alone. In each study, saxagliptin plus metformin provided significant (P<0.001) reductions in fasting plasma glucose and postprandial glucose, increased proportions of patients with therapeutic glycaemic response (HbA1c<7%), and was well tolerated with no increased incidence of hypoglycaemia compared with matched controls. Saxagliptin add-on or initial combination therapy with metformin provides significant and clinically meaningful reductions in key parameters of glycaemic control and is well tolerated in patients with inadequately controlled T2DM.
25 - 29 Apr 2009
European Society of Endocrinology