Endocrine Abstracts (2009) 20 P359

Saxagliptin either as add-on therapy to metformin or as initial combination therapy with metformin improves glycaemic control in patients with type 2 diabetes

Andreas Pfützner1, Irina Gurieva2, Mikhail Antsiferov3, Elsie Allen4, Shoba Ravichandran4 & Roland Chen4

1Institute for Clinical Research and Development, Mainz, Germany; 2Federal Bureau of Medicine and Social Expertise, Moscow, Russian Federation; 3Endocrinology Dispensary, Moscow, Russian Federation; 4Global Clinical Research, Bristol-Myers Squibb, Princeton, New Jersey, USA.

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 7.0–10.0%) or as initial combination therapy with metformin in drug-naïve T2DM patients (HbA1c 8.0–12.0%), 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 1–5) 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.

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