厄格列净对 2 型糖尿病和心力衰竭前期患者左心室功能的影响：Ertu-GLS 随机临床试验。

Effect of ertugliflozin on left ventricular function in type 2 diabetes and pre-heart failure: the Ertu-GLS randomized clinical trial.

机构信息

Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.

Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea.

出版信息

Cardiovasc Diabetol. 2024 Oct 22;23(1):373. doi: 10.1186/s12933-024-02463-0.

DOI:10.1186/s12933-024-02463-0

PMID:39438942

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11515769/

Abstract

BACKGROUND

The therapeutic effects of ertugliflozin, a sodium-glucose cotransporter 2 inhibitor, on cardiovascular outcome are not fully understood. This study aimed to evaluate the efficacy and safety of ertugliflozin on cardiac function in people with type 2 diabetes and pre-heart failure.

METHODS

We conducted a 24-week randomized, double-blind, placebo-controlled trial involving individuals with type 2 diabetes inadequately controlled with antidiabetic medications. Participants with left ventricular hypertrophy, E/e' >15, or impaired left ventricular global longitudinal strain (LVGLS) were randomized 1:1 to receive either ertugliflozin (5 mg once daily) or a placebo. The primary outcome was the change in LVGLS. Secondary outcomes included changes in left ventricular mass index (LVMI) and left ventricular ejection fraction (LVEF). Prespecified exploratory outcomes, including angiotensin-converting enzyme 2 (ACE2) and angiotensin (1-7) levels, were also assessed.

RESULTS

A total of 102 individuals (mean age, 63.9 ± 9.2 years; 38% women) were included. The ertugliflozin group showed a significant improvement in LVGLS (- 15.5 ± 3.1% to - 16.6 ± 2.8%, P = 0.004) compared to the placebo group (- 16.7 ± 2.7% to - 16.4 ± 2.6%, P = 0.509), with a significant between-group difference (P = 0.013). Improvements in LVMI and LVEF were also observed. Additionally, significant reductions in HbA, systolic blood pressure, whole-body and visceral fat, uric acid, proteinuria, N-terminal pro-B-type natriuretic peptide, and lipoprotein(a) were noted. ACE2 and angiotensin (1-7) levels significantly increased in the ertugliflozin group compared to the placebo group and correlated with changes in LVGLS [r = 0.456, P < 0.001 for ACE2; r = 0.541, P < 0.001 for angiotensin (1-7)]. Adverse events were similar between the two groups.

CONCLUSIONS

This study demonstrated that ertugliflozin has beneficial effects on left ventricular function in individuals with type 2 diabetes and pre-heart failure, and it provided insights into potential underlying mechanisms.

CLINICAL TRIAL REGISTRATION

ClinicalTrials.gov Identifier: NCT03717194.

摘要

背景

钠-葡萄糖共转运蛋白 2 抑制剂依格列净的治疗效果对心血管结局的影响尚未完全明确。本研究旨在评估依格列净对 2 型糖尿病合并心力衰竭前期患者心功能的疗效和安全性。

方法

我们开展了一项 24 周的随机、双盲、安慰剂对照临床试验，纳入了接受抗糖尿病药物治疗但血糖控制仍不充分的 2 型糖尿病患者。左心室肥厚、E/e' >15 或左心室整体纵向应变（LVGLS）受损的患者按 1:1 比例随机分配至接受依格列净（5 mg 每日 1 次）或安慰剂治疗。主要结局为 LVGLS 的变化。次要结局包括左心室质量指数（LVMI）和左心室射血分数（LVEF）的变化。还评估了血管紧张素转换酶 2（ACE2）和血管紧张素（1-7）水平等预设的探索性结局。

结果

共纳入 102 例患者（平均年龄 63.9±9.2 岁，38%为女性）。依格列净组的 LVGLS 较安慰剂组改善更明显（-15.5±3.1%比-16.7±2.7%，P=0.004），两组间差异有统计学意义（P=0.013）。LVMI 和 LVEF 也有所改善。此外，还观察到 HbA、收缩压、全身和内脏脂肪、尿酸、蛋白尿、N 末端脑钠肽前体和脂蛋白（a）的显著降低。与安慰剂组相比，依格列净组的 ACE2 和血管紧张素（1-7）水平显著升高，且与 LVGLS 的变化呈正相关（ACE2：r=0.456，P<0.001；血管紧张素（1-7）：r=0.541，P<0.001）。两组的不良反应相似。