A randomized controlled trial of the efficacy and safety of twice-daily saxagliptin plus metformin combination therapy in patients with type 2 diabetes and inadequate glycemic control on metformin monotherapy

To compare the safety and efficacy of saxagliptin 2.5 mg twice daily (BID) versus placebo add-on therapy to metformin immediate release (IR) in patients with type 2 diabetes and inadequate glycemic control with metformin alone.

This multicenter, 12-week, double-blind, parallel-group trial enrolled adult outpatients with type 2 diabetes (glycated hemoglobin [HbA_1c] 7.0%–10.0%) on stable metformin IR monotherapy (≥1500 mg, BID for ≥8 weeks). Patients were randomized to double-blind saxagliptin 2.5 mg BID or placebo added on to metformin IR following a 2-week, single-blind, placebo add-on therapy lead-in period. The primary end point was the change from baseline to week 12 in HbA_1c. Key secondary end points included change from baseline to week 12 in fasting plasma glucose (FPG) and the proportion of patients achieving HbA_1c <7.0% or HbA_1c ≤ 6.5% at week 12. Efficacy was analyzed in all patients who received randomized study drug with ≥1 postbaseline assessment. Safety was assessed in all treated patients.

In total, 74 patients were randomized to double-blind saxagliptin add-on therapy and 86 to placebo add-on therapy. At week 12, least-squares mean changes (95% CI) from baseline HbA_1c (adjusted for baseline HbA_1c) were significantly greater (P = 0.006) in the saxagliptin + metformin group -0.56% (-0.74% to -0.38%) versus the placebo + metformin group -0.22% (-0.39% to -0.06%). Adjusted mean changes from baseline in FPG were numerically greater with saxagliptin versus placebo; the difference (95% CI) -9.5 mg/dL (-21.7 to 2.7) was not statistically significant (P = 0.12). A numerically greater proportion of patients in the saxagliptin group than the placebo group achieved HbA_1c < 7.0% (37.5% vs 24.2%) or HbA_1c ≤6.5% (24.6% vs 10.7%). There were no unexpected safety findings. Hypoglycemia occurred in 4 patients (5.4%) in the saxagliptin group and 1 patient (1.2%) in the placebo group; confirmed hypoglycemia (symptoms plus fingerstick glucose ≤50 mg/dL) occurred in 1 patient in the placebo group.

Addition of saxagliptin 2.5 mg BID to metformin therapy in patients with type 2 diabetes and inadequate glycemic control on metformin monotherapy reduced HbA_1c compared with placebo added to metformin, with an adverse events profile similar to placebo and no unexpected safety findings.

ClinicalTrials.gov NCT00885378