Background: The mechanism of action of dipeptidyl peptidase-4 inhibitors, such as saxagliptin, makes them suitable for combination therapy in type 2 diabetes mellitus (T2DM). Genetic, cultural, and environmental differences in individuals from different regions of the world may result in differences in treatment response to oral antidiabetic drugs (OADs). This post-hoc subanalysis assessed the efficacy and safety of saxagliptin as add-on therapy to metformin, glyburide, or a thiazolidinedione in patients with inadequately controlled T2DM in the United States.
Methods: In 3 phase 3 studies of patients with T2DM uncontrolled on monotherapy, 547 adult US patients were randomized to receive saxagliptin (2.5 or 5 mg/d) or placebo as add-on to metformin, glyburide, or a thiazolidinedione (pioglitazone or rosiglitazone). Efficacy was assessed as the change from baseline to week 24 in glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), and postprandial glucose area under the curve (PPG-AUC) and the proportion of patients achieving HbA1c<7.0%. Pooled safety and tolerability data across trials were also analyzed.
Results: Reductions from baseline to week 24 in HbA1c were observed in all saxagliptin treatment groups versus placebo: saxagliptin 2.5 or 5 mg plus metformin (mean difference from placebo, -0.87% and -0.89%, respectively), glyburide (-0.51% and -0.52%), or thiazolidinedione (-0.45% and -0.60%). Improvement was also observed in FPG and PPG-AUC. Adverse events for the US cohort were consistent with previously reported data from the 3 trials. The pooled incidence of reported hypoglycemia was 5.3% and 11.4% with saxagliptin 2.5 and 5 mg/d add-on, respectively, versus 6.8% with placebo add-on.
Conclusions: This post-hoc analysis in a cohort of US patients with T2DM uncontrolled on monotherapy suggests that saxagliptin 2.5 or 5 mg as add-on therapy to OADs results in improvement across key glycemic parameters compared with placebo add-on and was generally safe and well tolerated.
Trial registration: ClinicalTrials.gov NCT00121667 NCT00295633 NCT00313313.