Novartis Pharma AG, Basel, Switzerland.
Diabetes Obes Metab. 2010 Jun;12(6):485-94. doi: 10.1111/j.1463-1326.2010.01215.x.
To assess the cardiovascular and cerebrovascular (CCV) safety of the dipeptidyl peptidase-IV inhibitor vildagliptin.
Data were pooled from 25 Phase III studies of vildagliptin, used either as monotherapy or combination therapy, with durations of 12 weeks to > or = 2 years. The safety of vildagliptin [50 mg qd (N = 1393) or 50 mg bid (N = 6116)] was assessed relative to a pool of all comparators [both placebo and active comparators (N = 6061)]. CCV events were adjudicated in a prospective, blinded fashion by an independent CCV adjudication committee. Meta-analysis of confirmed CCV events was performed with Mantel-Haenszel risk ratios (RRs); categories included in the composite endpoint were acute coronary syndrome, transient ischaemic attack (with imaging evidence of infarction), stroke and CCV death. Subgroup analyses by age (< and > or = 65 years), gender and cardiovascular (CV) risk status [high CV risk status defined as a previous history of events in the Standard MedDRA Queries of ischaemic heart disease, cardiac failure, ischaemic cerebrovascular conditions and/or embolic/thrombotic events, arterial) were also carried out. In addition, unadjusted and exposure-adjusted incidences are presented for both the composite endpoint and its components.
Relative to all comparators, the RRs for the composite endpoint were < 1 for both vildagliptin 50 mg qd [RR = 0.88; 95% CI (0.37, 2.11)] and vildagliptin 50 mg bid [RR = 0.84; 95% CI (0.62, 1.14)]. The results were consistent across subgroups defined by age, gender and CV risk status, including the higher CV risk subgroups of elderly patients [RR for vildagliptin 50 mg bid vs. all comparators = 1.04; 95% CI (0.62, 1.73)], males [RR = 0.87; 95% CI (0.60, 1.24)] or patients with a high CV risk status [RR = 0.78; 95% CI (0.51, 1.19)]. The exposure-adjusted incidences of each component of the composite endpoint for vildagliptin 50 mg bid were also lower than or similar to those of all comparators.
In a large meta-analysis, vildagliptin was not associated with an increased risk of adjudicated CCV events relative to all comparators in the broad population of type 2 diabetes including patients at increased risk of CCV events.
评估二肽基肽酶-4 抑制剂维格列汀的心血管和脑血管（CCV）安全性。
汇总了 25 项维格列汀的 III 期研究数据，这些研究均为维格列汀单药或联合治疗，持续时间为 12 周至≥2 年。维格列汀[50mg，qd（N=1393）或 50mg，bid（N=6116）]的安全性与所有对照药（安慰剂和活性对照药[N=6061]）进行了比较。采用前瞻性、盲法的方法，由独立的 CCV 裁决委员会对 CCV 事件进行裁决。采用 Mantel-Haenszel 风险比（RR）对确认的 CCV 事件进行荟萃分析；复合终点包括急性冠状动脉综合征、短暂性脑缺血发作（伴有梗死的影像学证据）、中风和 CCV 死亡。还进行了年龄（<65 岁和≥65 岁）、性别和心血管（CV）风险状况（高 CV 风险状态定义为既往发生缺血性心脏病、心力衰竭、缺血性脑血管疾病和/或栓塞/血栓事件、动脉）的亚组分析。此外，还报告了复合终点及其组成部分的未经调整和暴露调整发生率。
与所有对照药相比，维格列汀 50mg，qd [RR=0.88；95%CI（0.37，2.11）]和维格列汀 50mg，bid [RR=0.84；95%CI（0.62，1.14）]的复合终点 RR<1。这些结果在按年龄、性别和 CV 风险状况定义的亚组中是一致的，包括年龄较大的患者（维格列汀 50mg，bid 与所有对照药比较的 RR=1.04；95%CI（0.62，1.73））、男性（RR=0.87；95%CI（0.60，1.24））或具有高 CV 风险状态的患者（RR=0.78；95%CI（0.51，1.19））。维格列汀 50mg，bid 的复合终点各组成部分的暴露调整发生率也低于或与所有对照药相似。
在一项大型荟萃分析中，与广泛的 2 型糖尿病患者（包括 CCV 事件风险增加的患者）中的所有对照药相比，维格列汀与 CCV 事件的风险增加无关。
