Effects of GLP-1 Receptor Agonists on Heart Rate and the Autonomic Nervous System Using Holter Electrocardiography and Power Spectrum Analysis of Heart Rate Variability

Long- and short-acting glucagon-like peptide 1 receptor agonists (GLP-1RAs) liraglutide and lixisenatide, which are available for diabetes therapy, may act on the autonomic nervous system to increase heart rate (1,2). We performed a prospective, single-center, randomized, open-label study with a 1:1 allocation ratio using a 24-h Holter electrocardiogram to compare the effects of these GLP-1RAs on the autonomic nervous system. All procedures were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 and 2008. Informed consent was obtained from all patients participating in this study. The study is registered at University Hospital Medical Information Network Clinical Trials Registry (UMIN000017770). Sixty patients with type 2 diabetes who were admitted for diabetes treatment and had not received dipeptidyl peptidase-4 inhibitors or GLP-1RAs were randomly divided into a liraglutide (age 64.9 ± 12.7 years, HbA1c 10.3 ± 2.5% [89.1 mmol/mol], BMI 24.6 ± 4.8 kg/m2, diabetes duration 7.8 ± 7.8 years) or …