短期胰高血糖素样肽-1受体激动剂治疗改善代谢但不能改善2型糖尿病患者的心脏舒张功能障碍：一项随机、双盲、安慰剂对照试验。

Metabolic improvement with short-term, glucagon-like peptide-1 receptor agonist treatment does not improve cardiac diastolic dysfunction in patients with type 2 diabetes: A randomized, double-blind, placebo-controlled trial.

作者信息

Bojer Annemie Stege, Sørensen Martin Heyn, Bjerre Jenny, Gaede Peter, Vejlstrup Niels, Madsen Per Lav

机构信息

Department of Cardiology and Endocrinology, Slagelse Hospital, Slagelse, Denmark.

Institute of Regional Health Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark.

出版信息

Diabetes Obes Metab. 2021 Oct;23(10):2374-2384. doi: 10.1111/dom.14480. Epub 2021 Jul 26.

DOI:10.1111/dom.14480

PMID:34189832

Abstract

AIM

To investigate if short-term treatment with liraglutide, a glucagon-like peptide-1 receptor agonist, improves left ventricular diastolic function.

MATERIALS AND METHODS

An investigator-initiated, double-blind, randomized, placebo-controlled trial on the effect of 18 weeks of treatment with liraglutide on diastolic function was assessed in patients with type 2 diabetes with signs of diastolic dysfunction (echo-Doppler determined E/e' ≥ 9 and/or lateral e' ≤ 10 cm/s). Primary outcomes were improved left ventricle filling (the early peak filling rate [ePFR]) and left atrium ease of emptying (the passive emptying fraction [LA ]), assessed by cardiac magnetic resonance imaging at rest and during chronotropic stress. Secondary outcomes included left ventricular and left atrial volumes and systolic function, measures of aortic stiffness and echocardiographic diastolic variables.

RESULTS

Forty patients were randomized to liraglutide subcutaneously 1.8 mg/day (n = 20) or placebo (n = 20). Liraglutide reduced HbA1c (-0.47%, 95% CI [-0.88% to -0.06%] [-5.1, 95% CI {-9.7 to -0.62} mmol/mol]) and weight (-2.9, 95% CI [-4.6 to -1.2] kg); both P < .03. Liraglutide did not change ePFR at rest (-24 ± 60 vs. -6 ± 46 mL/s), during stress (2 ± 58 vs. -2 ± 38 mL/s), or the changes from rest to stress (12.9 ± 72.5 vs. 4.7 ± 104.0; all P > .05). LA decreased with liraglutide during stress (-3.1% [-9.0%, 1.1%] vs. 1.0% [-2.9%, 6.1%]; P = .049), but no changes were evident at rest (-4.3% [-7.9%, 1.9%] vs. -0.6% [-3.1%, 2.2%]; P = .19), or for the changes from rest to stress (-1.7 ± 8.4 vs. 0.8 ± 8.2; P = .4). Secondary outcomes were unchanged by liraglutide.

CONCLUSIONS

Short-term treatment with liraglutide did not improve left ventricular diastolic function, suggesting the cardioprotective effect is not exerted through the improvement in diastolic dysfunction.

摘要

目的

研究胰高血糖素样肽-1受体激动剂利拉鲁肽的短期治疗是否能改善左心室舒张功能。

材料与方法

在有舒张功能障碍体征（超声多普勒测定E/e'≥9和/或侧壁e'≤10cm/s）的2型糖尿病患者中，开展了一项由研究者发起的、双盲、随机、安慰剂对照试验，评估利拉鲁肽治疗18周对舒张功能的影响。主要结局指标为静息和变时应激时通过心脏磁共振成像评估的左心室充盈改善情况（早期峰值充盈率[ePFR]）和左心房排空容易程度（被动排空分数[LA]）。次要结局指标包括左心室和左心房容积及收缩功能、主动脉僵硬度指标和超声心动图舒张变量。

结果

40例患者被随机分为皮下注射利拉鲁肽1.8mg/天组（n = 20）和安慰剂组（n = 20）。利拉鲁肽降低了糖化血红蛋白（-0.47%，95%CI[-0.88%至-0.06%][-5.1，95%CI{-9.7至-0.62}mmol/mol]）和体重（-2.9，95%CI[-4.6至-1.2]kg）；两者P均<0.03。利拉鲁肽在静息时（-24±60对-6±46mL/s）、应激时（2±58对-2±38mL/s）或从静息到应激的变化（12.9±72.5对4.7±104.0）均未改变ePFR；所有P>0.05。应激期间利拉鲁肽使LA降低（-3.1%[-9.0%，1.1%]对1.0%[-2.9%，6.1%]；P = 0.049），但静息时无明显变化（-4.3%[-7.9%，1.9%]对-0.6%[-3.1%，2.2%]；P = 0.19），从静息到应激的变化也无明显差异（-1.7±8.4对0.8±8.2；P = 0.4）。利拉鲁肽对次要结局指标无影响。