Objective: To evaluate the efficacy and safety of once-daily saxagliptin monotherapy in treatment-naïve patients with type 2 diabetes (T2D) and inadequate glycemic control.
Research design and methods: This study included a main treatment cohort (MTC) with 401 patients (HbA(1c) > or = 7% and < or =10%) randomized and treated with oral saxagliptin 2.5, 5, or 10 mg once daily or placebo for 24 weeks and a separate open-label cohort (OLC) with 66 patients (HbA(1c) > 10% and < or =12%) who received saxagliptin 10 mg once daily for 24 weeks. Primary endpoint was HbA(1c) change from baseline to week 24. Secondary endpoints included change from baseline to week 24 in fasting plasma glucose (FPG), proportion of patients achieving HbA(1c) < 7%, and changes in postprandial glucose area-under-the-curve (PPG-AUC). Efficacy analyses for continuous variables were performed using an ANCOVA model with last-observation-carried-forward methodology.
Results: In the MTC, saxagliptin demonstrated statistically significant decreases in adjusted mean HbA(1c) changes from baseline (mean, 7.9%) to week 24 (-0.43%, -0.46%, -0.54%) for saxagliptin 2.5, 5, and 10 mg, respectively, vs. +0.19% for placebo (all p < 0.0001). Adjusted mean FPG was significantly reduced from baseline (-15, -9, -17 mg/dL) for saxagliptin 2.5, 5, and 10 mg, respectively, vs. +6 mg/dL for placebo (p = 0.0002, p = 0.0074, p < 0.0001, respectively). More saxagliptin-treated patients achieved HbA(1c) < 7% at week 24 (35% [p = NS], 38% [p = 0.0443], 41% [p = 0.0133]) for saxagliptin 2.5, 5, and 10 mg, respectively, than placebo (24%). PPG-AUC was reduced for saxagliptin 2.5, 5, and 10 mg (-6868, -6896, -8084 mg x min/dL, respectively) vs. placebo (-647 mg x min/dL) with statistical significance demonstrated for saxagliptin 5 mg (p = 0.0002) and 10 mg (p < 0.0001). HbA(1c), FPG, and PPG-AUC reductions were also observed in the OLC at 24 weeks. In the MTC, adverse event frequency was similar across all study arms. No cases of confirmed hypoglycemia (symptoms, with fingerstick glucose < or =50 mg/dL) were observed in either cohort. Saxagliptin was not associated with weight gain. Study limitations included the lack of a control group for the OLC and the use of prespecified rescue criteria, which limited the exposure time during which patients could remain on their originally randomized medication without the introduction of additional antihyperglycemic rescue treatment.
Conclusions: Once-daily saxagliptin monotherapy for 24 weeks was generally well tolerated and demonstrated clinically meaningful reductions in key parameters of glycemic control vs. placebo.
Trial registration: Clinical Trials NCT00121641