Division of Endocrinology and Metabolism, Li Ka Shing Knowledge Institute and Keenan Research Centre for Biomedical Science, St. Michael's Hospital, University of Toronto, Toronto, ON, Canada
Division of Endocrinology and Metabolism, Li Ka Shing Knowledge Institute and Keenan Research Centre for Biomedical Science, St. Michael's Hospital, University of Toronto, Toronto, ON, Canada Division of Cardiac Surgery, Li Ka Shing Knowledge Institute and Keenan Research Centre for Biomedical Science, St. Michael's Hospital, University of Toronto, Toronto, ON, Canada.
Diabetes Care. 2015 Jun;38(6):1145-53. doi: 10.2337/dc14-2868. Epub 2015 Mar 10.
To examine the safety and cardiovascular (CV) effects of saxagliptin in the predefined 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.
Individuals ≥40 years (n = 16,492; elderly, n = 8,561; very elderly, n = 2,330) with HbA1c ≥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.
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 HbA1c ≥7.6% (59.6 mmol/mol), the mean change from baseline HbA1c at 2 years was -0.69%, -0.64%, -0.66%, and -0.66% 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.
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.
在糖尿病患者心血管结局评估与 saxagliptin 干预的 SAVOR-TIMI 53 试验（Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus-Thrombolysis in Myocardial Infarction 53）中，检查 saxagliptin 在预先设定的老年（≥65 岁）和非常老年（≥75 岁）亚组人群中的安全性和心血管（CV）效应。
纳入年龄≥40 岁（n=16492；老年组，n=8561；非常老年组，n=2330）、糖化血红蛋白（HbA1c）≥6.5%（47.5mmol/mol）且≤12.0%（107.7mmol/mol）的个体，以 1:1 的比例随机分配至 saxagliptin（每日 5 或 2.5mg）或安慰剂组，进行一项中位随访时间为 2.1 年的双盲试验。
老年患者的主要终点（心血管死亡、心肌梗死或缺血性卒中的复合终点）比较 saxagliptin 与安慰剂的风险比（HR）为 0.92，而＜65 岁患者的 HR 为 1.15（P=0.06），非常老年患者的 HR 为 0.95。整个队列、老年队列和非常老年队列的次要复合终点 HR 相似。尽管 saxagliptin 增加了整个 saxagliptin 人群因心力衰竭住院的风险，但年龄与治疗之间无交互作用（老年患者 vs.＜65 岁患者，P=0.76；非常老年患者 vs.＜75 岁患者，P=0.34）。在基线 HbA1c≥7.6%（59.6mmol/mol）的 saxagliptin 治疗个体中，2 年时基线 HbA1c 的平均变化分别为-0.69%、-0.64%、-0.66%和-0.66%，年龄分别为≥65 岁、＜65 岁、≥75 岁和＜75 岁。所有队列中，saxagliptin 与安慰剂的总体不良事件（AE）和严重 AE 发生率相似；然而，无论年龄如何，saxagliptin 组的低血糖事件发生率均高于安慰剂组。
SAVOR-TIMI 53 试验支持 saxagliptin 在大量老年和非常老年参与者中的总体 CV 安全性，尽管不论年龄类别，心力衰竭住院的风险均增加。老年患者 saxagliptin 的 AE 和严重 AE 以及血糖疗效与年轻患者相似。
