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Effects of Liraglutide on Heart Rate and Heart Rate Variability: A Randomized, Double-Blind, Placebo-Controlled
Preman Kumarathurai1, Christian Anholm2, Bjørn S Larsen3
1Department of Cardiology, Copenhagen University Hospital of Bispebjerg, Copenhagen, Denmark preman.kumarathurai@dadlnet.dk.
Insights
Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) like liraglutide increase heart rate and reduce heart rate variability in patients with type 2 diabetes and coronary artery disease. This suggests potential effects on the sympathovagal balance.
Area of Science:
- Cardiology
- Endocrinology
- Pharmacology
Background:
- Reduced heart rate variability (HRV) and increased heart rate (HR) are linked to cardiovascular mortality.
- Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are known to increase HR and may potentially decrease HRV.
Purpose of the Study:
- To investigate the impact of the GLP-1 RA liraglutide on HRV and diurnal HR variation.
- To assess these effects in overweight patients with newly diagnosed type 2 diabetes (T2D) and stable coronary artery disease (CAD).
Main Methods:
- A 12 + 12-week double-blind, placebo-controlled crossover study.
- Administration of liraglutide or placebo alongside metformin.
- Assessment of HRV using 24-h Holter monitoring (SDNN, RMSSD, HF, LF/HF ratio).
Main Results:
- Liraglutide significantly decreased SDNN and RMSSD, indicating reduced HRV.
- Liraglutide increased mean, daytime, and nighttime HR.
- A reduction in high-frequency power (HF) was observed, suggesting a potential impact on parasympathetic activity.
Conclusions:
- Liraglutide increases HR and reduces HRV in patients with T2D and CAD, even with weight loss and metabolic improvements.
- The observed changes, particularly the increased nightly HR and reduced parasympathetic activity markers, suggest liraglutide may influence sympathovagal balance.
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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