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

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

*Kontaktforfatter for dette arbejde

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Abstrakt

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.

OriginalsprogEngelsk
TidsskriftDiabetes, Obesity and Metabolism
Vol/bind23
Udgave nummer10
Sider (fra-til)2374-2384
ISSN1462-8902
DOI
StatusUdgivet - okt. 2021

Bibliografisk note

Funding Information:
The authors would like to acknowledge the patients volunteering in the study. Further, we would like to acknowledge the nurses and secretaries in the Department of Endocrinology and Cardiology at NSR hospital, as well as the Department of Radiology at Rigshospitalet, especially CMR technician Karen Larsen for assistance in this work. ASB received funding from the local research committee at NSR hospital, the Region Zealand Research Committee [13–000835], and the Danish Heart Association [16‐R107‐A6790‐22002 and 18‐R125‐A8444‐22110]. Novo Nordisk supported the study with an unrestricted grant covering the costs of CMR scans and blood analyses, and provided free study medication. None of the funding sources played any role in the process of conduction, interpretation of results or publishing the study.

Publisher Copyright:
© 2021 John Wiley & Sons Ltd.

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