Boaz Hirshberg, Brian Bryzinski, John Xu and Nayyar Iqbal
Objective: Saxagliptin is a once-daily, orally administered dipeptidyl peptidase-4 inhibitor, approved for the treatment of type 2 diabetes mellitus (T2DM). In 4 double-blind, placebo-controlled, phase 3 trials, saxagliptin 2.5 or 5 mg significantly reduced glycated hemoglobin (HbA1c) from baseline at 24 weeks. A pooled analysis of these clinical trials was conducted to assess the therapeutic profile of saxagliptin monotherapy.
Methods: A post hoc pooled analysis of 4 saxagliptin monotherapy trials in patients with T2DM was conducted to determine the consistency of treatment effects, assessed as change from baseline in HbA1c at week 24, in patient subgroups stratified by race, sex, age, and baseline HbA1c. Secondary end points included change from baseline at week 24 in fasting plasma glucose and proportion of patients achieving HbA1c <7%. Safety assessments included adverse event reports, laboratory test results, and vital sign measurements.
Results: At week 24, saxagliptin 2.5 mg, saxagliptin 5 mg, and placebo decreased HbA1c from baseline by −0.66%, −0.64%, and −0.13% respectively (P<0.0001 for each saxagliptin dose vs placebo). The treatment effects of saxagliptin 2.5 5 mg on HbA1c were consistent across subgroups, and no treatment interactions were observed, with the exception of baseline HbA1c (P=0.003). The overall occurrence of adverse events was similar among groups (66.0% saxagliptin 2.5 mg; 53.0% saxagliptin 5 mg; 45.3% placebo). The incidence of hypoglycemic events was low and comparable among groups, and no cases of confirmed hypoglycemia were reported.
Conclusions: Consistent with findings from individual studies, this pooled analysis showed saxagliptin to significantly improve glycemic measures compared with placebo. Outcomes confirmed saxagliptin treatment was associated with a weight-neutral effect and a low risk for hypoglycemia. Based on the overall findings, saxagliptin has a favorable benefit:risk profile and may be considered an alternative first-line therapy for patients with T2DM in whom metformin is contraindicated or not tolerated.