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Cited by 96Heart Rate Variability and Autonomic ControlDiabetes Treatment and ManagementCardiovascular Function and Risk Factors

Effects of Liraglutide on Heart Rate and Heart Rate Variability: A Randomized, Double-Blind, Placebo-Controlled Crossover Study

Kumarathurai, Preman, Anholm, Christian, Larsen, Bjørn S., Olsen, Rasmus Huan, Madsbad, Sten, Kristiansen, Ole, Nielsen, Olav W., Haugaard, Steen B. +1 more·2017·Diabetes Care
DOI 10.2337/dc16-1580
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Abstract

OBJECTIVE: Reduced heart rate variability (HRV) and increased heart rate (HR) have been associated with cardiovascular mortality. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) increase HR, and studies have suggested that they may reduce HRV. We examined the effect of the GLP-1 RA liraglutide on HRV and diurnal variation of HR in overweight patients with newly diagnosed type 2 diabetes (T2D) and stable coronary artery disease (CAD). RESEARCH DESIGN AND METHODS: Liraglutide or placebo was administrated to a backbone therapy of metformin in this double-blind, placebo-controlled 12 + 12–week crossover study. SD of beat-to-beat (NN) intervals (SDNN) was assessed by 24-h Holter monitoring as a measure of HRV. Diurnal HR variation and sympathovagal balance analyzed by root mean square of successive differences (RMSSD) in NN intervals and high-frequency (HF) and low-frequency (LF) power were assessed. RESULTS: Compared with placebo, liraglutide decreased SDNN in 27 subjects (−33.9 ms; P < 0.001, paired analysis); decreased RMSSD (−0.3 log-ms; P = 0.025); and increased the mean HR (8.1 beats/min; P = 0.003), daytime HR (5.7; P = 0.083), and nighttime HR (6.3; P = 0.026). In a multivariable regression analysis, the decrease in SDNN remained significant after adjustment for metabolic and HR changes. Liraglutide reduced HF power (−0.7 log-ms2; P = 0.026) without any change in LF/HF ratio. CONCLUSIONS: In overweight patients with CAD and newly diagnosed T2D, liraglutide increased HR and reduced HRV despite significant weight loss and improvement in metabolic parameters. The increase in nightly HR in conjunction with a decrease in parameters of parasympathetic activity suggests that liraglutide may affect sympathovagal balance.

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  • Discrepant findings are available for activation of the cardiac sympathetic nervous system.

    “Similarly, discrepant findings are available for activation of the (cardiac) sympathetic nervous system”

    From Safety of Semaglutide (2021) · cites this paper as [109]

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Authors
Kumarathurai, P., Anholm, C., Larsen, B. S., Olsen, R. H., Madsbad, S., Kristiansen, O., Nielsen, O. W., Haugaard, S. B., & Sajadieh, A.
Affiliations
  • Bispebjerg Hospital (DK)
  • Amager Hospital (DK)
  • Hvidovre Hospital (DK)
Corresponding author
Kumarathurai, Preman
ORCID
Venue
Diabetes Care
Publisher
American Diabetes Association
Published
2016-10-19
Volume
40
Issue
1
Pages
117-124
ISSN
  • 0149-5992 (ISSN-L)
  • 1935-5548
DOI
10.2337/dc16-1580
OpenAlex
W2535492942
Cited by
96
References
9
Citations by year
2026: 11 · 2025: 6 · 2024: 6 · 2023: 10 · 2022: 5 · 2021: 11 · 2020: 5 · 2019: 20 · 2018: 11 · 2017: 11
FWCI
11.52
Type
journal article
Language
en
Open access
closed
Licence
www.diabetesjournals.org/content/license (vor, 62 d)
Locations
  • Diabetes Care (publishedVersion)
  • PubMed (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
Funders
  • Novo Nordisk (unrestricted grant for investigator-initiated studies)
  • Danish Heart Foundation
  • The AP Møller Foundation
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
Keywords
liraglutide, heart rate variability, heart rate, GLP-1 receptor agonists, type 2 diabetes, coronary artery disease, sympathovagal balance, parasympathetic activity, metformin, cardiovascular risk
MeSH terms
Liraglutide, Aged, Circadian Rhythm, Coronary Artery Disease, Diabetes Mellitus, Type 2, Double-Blind Method, Drug Therapy, Combination, Female, Heart Rate, Humans, Hypoglycemic Agents, Male, Metformin, Middle Aged, Electrocardiography, Ambulatory, Cross-Over Studies, Overweight

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