Heart rate variability in type 2 diabetic subjects randomized to liraglutide or glimepiride treatment, both in combination with metformin: A randomized, open, parallel‐group study

Abstract

Summary Aims Reduced heart rate variability (HRV) and increased heart rate (HR) are associated with cardiovascular (CV) mortality. In the Liraglutide Effect and Action in Diabetes outcome trial, it was demonstrated a lower rate of CV events in type 2 diabetes (T2D) patients treated with liraglutide compared to placebo. We aimed to investigate the effects of liraglutide compared with glimepiride treatment in T2D patients on the CV risk parameters HR and HRV. Methods This was a post hoc study whereas sixty‐two T2D individuals (45 males) were randomized to once daily 1.8 mg liraglutide or once daily 4 mg glimepiride, both in combination with 1 g metformin. HR and measurement of sympathetic activity, that is standard deviation (SD) of beat‐to‐beat (NN) intervals (SDNN), was assessed by 24‐hour Holter monitoring system. Parasympathetic activity was analysed by root mean square of successive differences (RMSSD) in NN intervals and high‐frequency (HF), low‐frequency (LF) and very low‐frequency power. Results Baseline clinical characteristics for liraglutide (n = 33) and glimepiride (n = 29) groups were well matched. There was a persistent increase in diurnal HR followed by a significantly increased HR at daytime 5.4 beats per minute, P = 0.011 in the liraglutide‐treated group. There was no treatment change between groups in SDNN and RMSSD, or in HF and LF frequency power analysis. Conclusions Liraglutide treatment increased diurnal variation in hourly mean HR followed by an increase in mean daytime HR, independently of changes in sympathetic or parasympathetic activity.

Effect of Metformin on Heart Rate Variability in Newly Diagnosed Type 2 Diabetes Mellitus Patients at a Tertiary Care Hospital

“…Sammito et al reported HF values between 16.41 and 31.92 power% for the age group of 20-60 years [11]. A recent study evaluating the effects of combination treatment of metformin with either liraglutide or glimepiride reported similar results with no significant changes in RMSSD, LF, and HF and LF/HF ratio with the oral hypoglycemic drugs [12].…”

Effect of the Glucagon-Like Peptide-1 Receptor Agonists on Autonomic Function in Subjects with Diabetes: A Systematic Review and Meta-Analysis

“…Among these, ten studies were excluded (reasons reported in Fig. 1) and six studies were enrolled [25][26][27][28][29][30] in the final analysis (Fig. 1).…”

“…This phenomenon is characterized by a "shift" of the sympatho-vagal balance with reduction of the LF component and no change in parasympathetic tone (HF) [26]. In contrast, Nystrom et al [30] demonstrated the absence of changes in sympathetic or parasympathetic activity evaluated by HRV in 62 T2DM individuals receiving 1.8 mg liraglutide once daily in comparison with 4 mg glimepiride once daily. Similarly, in the context of T1DM, changes neither in the HRV domains, nor in cardiac vagal tone and cardiac sensitivity to the baroreflex were observed in 19 patients treated with liraglutide for 26 weeks [25].…”

Effect of the Glucagon-like Peptide-1 Receptor (GLP-1R) Agonists on Autonomic Function in Subjects With Diabetes: a Systematic Review and Meta-analysis.

“…Among these, ten studies were excluded (reasons reported in Fig. 1) and six studies were enrolled [25][26][27][28][29][30] in the nal analysis ( Fig. 1).…”

“…This phenomenon is characterized by a "shift" of the sympatho-vagal balance with reduction of the LF component and no change in parasympathetic tone (HF) 26 . In contrast, Nystrom et al demonstrated the absence of changes in sympathetic or parasympathetic activity evaluated by HRV in 62 T2DM individuals receiving 1.8 mg liraglutide once daily in comparison with 4 mg glimepiride once daily 30 . Similarly, in the context of type 1 DM (T1DM), changes neither in the HRV domains, nor in cardiac vagal tone and cardiac sensitivity to the barore ex were observed in 19 patients treated with liraglutide for 26 weeks 25 .…”