Department of Medicine/Division of Cardiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
Cardiology Division, Stony Brook University, Stony Brook, New York.
J Am Coll Cardiol. 2017 Aug 8;70(6):704-712. doi: 10.1016/j.jacc.2017.06.016. Epub 2017 Jun 12.
Sodium glucose co-transporter 2 inhibitors may reduce cardiovascular and heart failure risk in patients with type 2 diabetes mellitus (T2DM).
The goal of this study was to examine the effects of canagliflozin on cardiovascular biomarkers in older patients with T2DM.
In 666 T2DM patients randomized to receive canagliflozin 100 or 300 mg or placebo, the study assessed the median percent change in serum N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity troponin I (hsTnI), soluble (s)ST2, and galectin-3 from baseline to 26, 52, and 104 weeks.
Both serum NT-proBNP and serum hsTnI levels increased in placebo recipients, but they remained largely unchanged in those randomized to canagliflozin. Hodges-Lehmann estimates of the difference in median percent change between pooled canagliflozin and placebo were -15.0%, -16.1%, and -26.8% for NT-proBNP, and -8.3%, -11.9%, and -10.0% for hsTnI at weeks 26, 52, and 104, respectively (all p < 0.05). Serum sST2 was unchanged with canagliflozin and placebo over 104 weeks. Serum galectin-3 modestly increased from baseline with canagliflozin versus placebo, with significant differences observed at 26 and 52 weeks but not at 104 weeks. These results remained unchanged when only patients with complete samples were assessed.
Compared with placebo, treatment with canagliflozin delayed the rise in serum NT-proBNP and hsTnI for over 2 years in older T2DM patients. These cardiac biomarker data provide support for the beneficial cardiovascular effect of sodium glucose co-transporter 2 inhibitors in T2DM. (A Safety and Efficacy Study of Canagliflozin in Older Patients [55 to 80 Years of Age] With Type 2 Diabetes Mellitus; NCT01106651).
钠-葡萄糖共转运蛋白 2 抑制剂(SGLT2i)可能降低 2 型糖尿病(T2DM)患者的心血管和心力衰竭风险。
本研究旨在探讨卡格列净对老年 T2DM 患者心血管生物标志物的影响。
666 例 T2DM 患者被随机分为卡格列净 100mg 或 300mg 或安慰剂组,评估基线至 26、52 和 104 周时血清 N 末端 pro-B 型利钠肽(NT-proBNP)、高敏肌钙蛋白 I(hsTnI)、可溶性(s)ST2 和半乳糖凝集素-3 的中位数百分比变化。
安慰剂组血清 NT-proBNP 和血清 hsTnI 水平均升高,而卡格列净组则基本保持不变。卡格列净和安慰剂组之间的中位百分比变化差异的 Hodges-Lehmann 估计值分别为 NT-proBNP 为-15.0%、-16.1%和-26.8%,hsTnI 为-8.3%、-11.9%和-10.0%,在第 26、52 和 104 周时(均 p < 0.05)。卡格列净和安慰剂治疗 104 周时血清 sST2 无变化。卡格列净治疗组血清半乳糖凝集素-3 较基线略有升高,与安慰剂组相比,第 26 和 52 周时差异有统计学意义,但第 104 周时无差异。仅评估具有完整样本的患者时,结果保持不变。
与安慰剂相比,在老年 T2DM 患者中,卡格列净治疗超过 2 年可延缓血清 NT-proBNP 和 hsTnI 的升高。这些心脏生物标志物数据为 SGLT2i 在 T2DM 中的有益心血管作用提供了支持。(卡格列净在 55 至 80 岁 2 型糖尿病患者中的安全性和疗效研究;NCT01106651)。