Abstract
INTRODUCTION: Saxagliptin added to metformin extended release (XR) and uptitrated metformin XR were evaluated for their impact on daily glucose measurements and their tolerability in patients with type 2 diabetes mellitus (T2DM) inadequately controlled with metformin monotherapy. METHODS: Patients aged 18-78 years on metformin 850-1,500 mg with glycated hemoglobin (HbA1c) 7.5-11.5% at screening were eligible for this double-blind, active-controlled study. Patients were stabilized on metformin XR 1,500 mg before randomization. Patients with HbA1c 7-11% and fasting plasma glucose (FPG) ≥126 mg/dL after a 4- 8-week lead-in period were randomly assigned to saxagliptin 5 mg + metformin XR 1,500 mg or metformin XR 500 mg + metformin XR 1,500 mg (uptitrated metformin XR). The primary end point was change from baseline to week 4 in 24-h mean weighted glucose (MWG). Secondary end points were changes from baseline to week 4 in 2-h postprandial glucose (PPG) and FPG. RESULTS: At week 4, the adjusted mean ± SE change from baseline in 24-h MWG was -19.0 ± 5.7 mg/dL (95% CI -30.3 to -7.6) for saxagliptin + metformin XR and -8.2 ± 6.0 mg/dL (95% CI -20.0 to 3.7) for uptitrated metformin XR. Mean changes from baseline in 2-h PPG and FPG were numerically greater with saxagliptin + metformin XR versus uptitrated metformin XR. The incidence of adverse events was lower with saxagliptin + metformin XR (17.4%) versus uptitrated metformin XR (31.9%) mainly due to differences in gastrointestinal adverse event incidence (2.2% vs 10.6%, respectively). There were no reports of confirmed hypoglycemia in either group. CONCLUSION: In this 4-week study in patients with T2DM inadequately controlled with metformin monotherapy, saxagliptin added to metformin XR demonstrated a trend for improvement in measures of daily glycemic control, with fewer gastrointestinal adverse events, compared with uptitrated metformin.