Efficacy and Safety of Saxagliptin in Older Participants in the SAVOR-TIMI 53 Trial

OBJECTIVE To examine the safety and cardiovascular (CV) effects of saxagliptin in the pre-defined elderly (>= 65 years) and very elderly (>= 75 years) subpopulations of the Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus-Thrombolysis in Myocardial Infarction 53 (SAVOR-TIMI 53) trial. RESEARCH DESIGN AND METHODS Individuals >= 40 years (n = 16,492; elderly, n = 8,561; very elderly, n = 2,330) with HbA(1c) >= 6.5% (47.5 mmol/mol) and <= 12.0% (107.7 mmol/mol) were randomized (1: 1) to saxagliptin (5 or 2.5 mg daily) or placebo in a double-blind trial for a median follow-up of 2.1 years. RESULTS The hazard ratio (HR) for the comparison of saxagliptin versus placebo for the primary end point (composite of CV mortality, myocardial infarction, or ischemic stroke) was 0.92 for elderly patients vs. 1.15 for patients <65 years (P = 0.06) and 0.95 for very elderly patients. The HRs for the secondary composite end points in the entire cohort, elderly cohort, and very elderly cohort were similar. Although saxagliptin increased the risk of hospitalization for heart failure in the overall saxagliptin population, there was no age-based treatment interaction (P = 0.76 for elderly patients vs. those <65 years; P = 0.34 for very elderly patients vs. those <75 years). Among saxagliptin-treated individuals with baseline HbA(1c) >= 7.6% (59.6 mmol/mol), the mean change from baseline HbA(1c) at 2 years was 20.69%, 20.64%, 20.66%, and 20.66% for those >= 65, <65, >= 75, and <75 years old, respectively. The incidence of overall adverse events (AEs) and serious AEs was similar between saxagliptin and placebo in all cohorts; however, hypoglycemic events were higher for saxagliptin versus placebo regardless of age. CONCLUSIONS The SAVOR-TIMI 53 trial supports the overall CV safety of saxagliptin in a robust number of elderly and very elderly participants, although the risk of heart failure hospitalization was increased irrespective of age category. AEs and serious AEs as well as glycemic efficacy of saxagliptin in elderly patients are similar to those found in younger patients.