A Pooled Analysis of the Efficacy and Safety of Saxagliptin as Monotherapy in Patients with Type 2 Diabetes

Abstract

Current guidelines recommend dipeptidyl peptidase-4 inhibitors as an option for monotherapy in patients inadequately controlled by diet and exercise and for whom metformin is contraindicated or not tolerated. In 4 placebo (PBO)-controlled, phase 3, 24-week studies in treatment-naïve patients, monotherapy with saxagliptin (SAXA) 2.5 mg/d and 5 mg/d significantly reduced the primary end point of adjusted mean change from baseline in glycated hemoglobin (HbA1c) by -0.40% to -0.64% (difference vs. PBO). Secondary end points included fasting plasma glucose (FPG), 2-hour postprandial plasma glucose (PPG), and the proportion of patients achieving HbA1c <7%. This pooled analysis was performed to better characterize the results from the individual studies and to assess consistency of response across studies and subgroups. Patients (N=1306) had a mean age of 52 y and were predominantly Asian (65%) and men (53%), with a mean duration of diabetes of 1.5 y and mean baseline HbA1c of 8.1%. Data were analyzed using an analysis of covariance model and adjusted for baseline value and study. At week 24, the mean difference (95% CI) vs. PBO for HbA1c was -0.54% (-0.73%, -0.35%, P<0.0001) for SAXA 2.5 mg/d and -0.51% (-0.62%, -0.39%, P<0.0001) for SAXA 5 mg/d. The effects of SAXA on HbA1c were consistent across studies and subgroups of race, sex, age, and baseline HbA1c. Greater reductions in FPG and PPG, and a greater proportion of patients achieving HbA1c <7% were also observed with SAXA vs. PBO. The incidence of adverse events was slightly higher in patients receiving SAXA (2.5 mg, 66%; 5 mg, 53%) vs. PBO (45%) as was the incidence of reported hypoglycemia (SAXA, 2.5 mg, 4%; 5 mg 3%; PBO, 2%). There were no events of confirmed hypoglycemia (fingerstick glucose ≤50 mg/dL with symptoms). The results show that SAXA monotherapy is effective and well tolerated in patients with type 2 diabetes and is an appropriate alternative in patients for whom first-line treatment with metformin is inappropriate.