Diabetes Metab J.  2022 Nov;46(6):901-911. 10.4093/dmj.2021.0314.

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

• Greco C
• Santi D
• Brigante G
• Pacchioni C
• Simoni M

• KMID: 2536148
• DOI: http://doi.org/10.4093/dmj.2021.0314

Abstract

Background
In addition to the metabolic effects in diabetes, glucagon-like peptide 1 receptor (GLP-1R) agonists lead to a small but substantial increase in heart rate (HR). However, the GLP-1R actions on the autonomic nervous system (ANS) in diabetes remain debated. Therefore, this meta-analysis evaluates the effect of GLP-1R agonist on measures of ANS function in diabetes.
Methods
According to the Cochrane Collaboration and Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement, we conducted a meta-analysis considering clinical trials in which the autonomic function was evaluated in diabetic subjects chronically treated with GLP-1R agonists. The outcomes were the change of ANS function measured by heart rate variability (HRV) and cardiac autonomic reflex tests (CARTs).
Results
In the studies enrolled, HR significantly increased after treatment (P<0.001), whereas low frequency/high frequency ratio did not differ (P=0.410); no changes in other measures of HRV were detected. Considering CARTs, only the 30:15 value derived from lying-to-standing test was significantly lower after treatment (P=0.002), but only two studies reported this measurement. No differences in other CARTs outcome were observed.
Conclusion
The meta-analysis confirms the HR increase but seems to exclude an alteration of the sympatho-vagal balance due to chronic treatment with GLP-1R agonists in diabetes, considering the available measures of ANS function.

Keyword

Autonomic nervous system; Diabetes mellitus; Diabetic neuropathies; Glucagon-like peptide-1 receptor; Heart rate

Figure

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  Fig. 1. Flowchart of the study search and selection process.

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  Fig. 2. Low frequency/high frequency (LF/HF) ratio mean difference after the chronic administration of glucagon-like peptide 1 receptor agonists. LF/HF ratio mean difference after treatment in the entire sample (P=0.410) and considering only exenatide (P=0.290) or only liraglutide (P=0.930) treatment. SD, standard deviation; IV, inverse variance; CI, confidence interval.

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  Fig. 3. Heart rate (HR) mean difference before and after treatment. HR significantly increases after treatment (P<0.001), with a low heterogeneity rate (6%). SD, standard deviation; IV, inverse variance; CI, confidence interval.

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  Fig. 4. Standard deviations of RR interval (SDNN) mean difference after the glucagon-like peptide 1 receptor chronic administration comparing study and control groups. Significantly lower SDNN values were detected in the study-compared to control groups (P=0.040). SD, standard deviation; IV, inverse variance; CI, confidence interval.

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  Fig. 5. A 30:15 value standard mean difference after chronic glucagon-like peptide 1 receptor agonists treatment. SD, standard deviation; IV, inverse variance; CI, confidence interval.

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