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

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 people with diabetes remain still debated. Therefore, this meta-analysis evaluates the effect of GLP-1R agonist chronic treatment on measures of ANS function in people with diabetes. Methods. According to the Cochrane Collaboration and PRISMA statement, we conducted a meta-analysis considering clinical trials in which the autonomic function was evaluated in people with diabetes 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 present 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.