Effects of canagliflozin, a sodium glucose co-transporter 2 inhibitor, on blood pressure and markers of arterial stiffness in patients with type 2 diabetes mellitus: a post hoc analysis.
Effects of canagliflozin, a sodium glucose co-transporter 2 inhibitor, on blood pressure and markers of arterial stiffness in patients with type 2 diabetes mellitus: a post hoc analysis.
复制标题
DOI：
10.1186/s12933-017-0511-0
复制
发表时间：
2017-02-27
影响因子：
9.3
通讯作者：
Ren J
中科院分区：
文献类型：
--
作者：
Pfeifer M;Townsend RR;Davies MJ;Vijapurkar U;Ren J
生理决定因素，如脉压[收缩压（SBP）和舒张压（DBP）之差]、平均动脉压（2/3 DBP + 1/3 SBP）和双乘积[每分钟心跳次数（bpm）× SBP]与心血管结局相关。在2型糖尿病（T2 DM）患者中评估了卡格列净（一种钠葡萄糖协同转运蛋白2（SGLT 2）抑制剂）对脉压、平均动脉压和双乘积的影响。该事后分析基于4项在T2 DM患者（N = 2313）中评价卡格列净的26周、随机、双盲、安慰剂对照研究和1项在T2 DM和高血压患者（N = 169）中评价卡格列净的6周、随机、双盲、安慰剂对照、动态血压监测（ABPM）研究的汇总数据。使用坐位血压测量（汇总研究）或平均24小时血压评估（ABPM研究）评估SBP、DBP、脉压、平均动脉压和双乘积较基线的变化。根据不良事件报告评估安全性。在汇总研究中，与安慰剂相比，卡格列净100和300 mg在第26周降低SBP（−4.3和−5.0 vs −0.3 mmHg）和DBP（−2.5和−2.4 vs −0.6 mmHg）。与安慰剂相比，卡格列净100和300 mg组还观察到脉压（−1.8和−2.6 vs 0.2 mmHg）、平均动脉压（−3.1和−3.3 vs −0.5 mmHg）和双乘积（−381和−416 vs −30 bpm × mmHg）降低。在ABPM研究中，与安慰剂相比，卡格列净100和300 mg在第6周降低了平均24小时SBP（−4.5和−6.2 vs −1.2 mmHg）和DBP（−2.2和−3.2 vs −0.3 mmHg）。与安慰剂相比，卡格列净300 mg可降低脉压（−3.3 vs −0.8 mmHg）和平均动脉压（−4.2 vs −0.6 mmHg），而卡格列净100 mg对这些参数的影响更为温和。卡格列净在两个研究人群中通常耐受良好。卡格列净改善了所有三种心血管生理标志物，这与卡格列净可能对T2 DM患者的某些心血管结局具有有益作用的假设一致。 试用注册ClinicalTrials.gov标识符：NCT 01081834（2010年3月注册）; NCT 01106677（2010年4月注册）; NCT 01106625（2010年4月注册）; NCT 01106690（2010年4月注册）; NCT 01939496（2013年9月注册）
Physiologic determinants, such as pulse pressure [difference between systolic blood pressure (SBP) and diastolic BP (DBP)], mean arterial pressure (2/3 DBP + 1/3 SBP), and double product [beats per minute (bpm) × SBP], are linked to cardiovascular outcomes. The effects of canagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, on pulse pressure, mean arterial pressure, and double product were assessed in patients with type 2 diabetes mellitus (T2DM). This post hoc analysis was based on pooled data from four 26-week, randomized, double-blind, placebo-controlled studies evaluating canagliflozin in patients with T2DM (N = 2313) and a 6-week, randomized, double-blind, placebo-controlled, ambulatory BP monitoring (ABPM) study evaluating canagliflozin in patients with T2DM and hypertension (N = 169). Changes from baseline in SBP, DBP, pulse pressure, mean arterial pressure, and double product were assessed using seated BP measurements (pooled studies) or averaged 24-h BP assessments (ABPM study). Safety was assessed based on adverse event reports. In the pooled studies, canagliflozin 100 and 300 mg reduced SBP (−4.3 and −5.0 vs −0.3 mmHg) and DBP (−2.5 and −2.4 vs −0.6 mmHg) versus placebo at week 26. Reductions in pulse pressure (−1.8 and −2.6 vs 0.2 mmHg), mean arterial pressure (−3.1 and −3.3 vs −0.5 mmHg), and double product (−381 and −416 vs −30 bpm × mmHg) were also seen with canagliflozin 100 and 300 mg versus placebo. In the ABPM study, canagliflozin 100 and 300 mg reduced mean 24-h SBP (−4.5 and −6.2 vs −1.2 mmHg) and DBP (−2.2 and −3.2 vs −0.3 mmHg) versus placebo at week 6. Canagliflozin 300 mg provided reductions in pulse pressure (−3.3 vs −0.8 mmHg) and mean arterial pressure (−4.2 vs −0.6 mmHg) compared with placebo, while canagliflozin 100 mg had more modest effects on these parameters. Canagliflozin was generally well tolerated in both study populations. Canagliflozin improved all three cardiovascular physiologic markers, consistent with the hypothesis that canagliflozin may have beneficial effects on some cardiovascular outcomes in patients with T2DM. Trial registration ClinicalTrials.gov Identifier: NCT01081834 (registered March 2010); NCT01106677 (registered April 2010); NCT01106625 (registered April 2010); NCT01106690 (registered April 2010); NCT01939496 (registered September 2013)