Adding Saxagliptin to Metformin Extended Release (XR) or Uptitration of Metformin XR: Efficacy on Daily Glucose Measures

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.

Fig. 1

Study design. DB Double blind, FPG fasting plasma glucose, HbA _1c glycated hemoglobin, IR immediate release, MET XR metformin extended release, MWG mean weighted glucose, OL open label, SAXA saxagliptin

Fig. 2

Patient disposition. MET XR metformin extended release, SAXA saxagliptin

Fig. 3

The 24-h glucose profile at a baseline and b week 4 and mean change from baseline at c week 4 in 24-h glucose profile for patients receiving SAXA + MET XR and for patients receiving uptitrated MET XR. MET XR Metformin extended release, SAXA saxagliptin

Fig. 4

Mean glycated hemoglobin (HbA_1c) from screening to week 4. MET XR Metformin extended release, SAXA saxagliptin