TY - JOUR

T1 - Metabolic improvement with short-term, glucagon-like peptide-1 receptor agonist treatment does not improve cardiac diastolic dysfunction in patients with type 2 diabetes

T2 - A randomized, double-blind, placebo-controlled trial

AU - Bojer, Annemie Stege

AU - Sørensen, Martin Heyn

AU - Bjerre, Jenny

AU - Gæde, Peter

AU - Vejlstrup, Niels

AU - Madsen, Per Lav

N1 - Publisher Copyright: © 2021 John Wiley & Sons Ltd.

PY - 2021

Y1 - 2021

N2 - 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 [LAPEF]), 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). LAPEF 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.

AB - 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 [LAPEF]), 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). LAPEF 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.

KW - cardiac function

KW - cardiovascular magnetic resonance imaging

KW - diastolic function

KW - glucagon-like peptide-1 receptor agonist

KW - liraglutide

KW - type 2 diabetes

U2 - 10.1111/dom.14480

DO - 10.1111/dom.14480

M3 - Journal article

C2 - 34189832

AN - SCOPUS:85111287171

VL - 23

SP - 2374

EP - 2384

JO - Diabetes, Obesity and Metabolism

JF - Diabetes, Obesity and Metabolism

SN - 1462-8902

IS - 10

ER -