Dapagliflozin associates with heart rate variability decline in T2DM patients on GLP-1 receptor agonist therapy: a prospective observational study

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Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are associated with increased heart rate (HR) and reduced heart rate variability (HRV) in patients with type 2 diabetes mellitus (T2DM). While sodium-glucose co-transporter 2 inhibitors (SGLT2i) may exert beneficial effects on cardiac autonomic function, it remains uncertain whether baseline SGLT2i use is associated with attenuation of GLP-1 RA-related HRV decline in T2DM. Methods: In this prospective observational study, 45 patients with T2DM were divided into two groups according to pre-study dapagliflozin use: a dapagliflozin-naïve group (Control group, n=22) and a dapagliflozin-exposed group (DAPA group, n=23). All participants subsequently received GLP-1 RA therapy for 12 weeks. Changes in HRV parameters were assessed by 24-hour ambulatory electrocardiography before and after treatment. Between-group differences were further evaluated using analysis of covariance (ANCOVA), inverse probability of treatment weighting (IPTW), and multivariable linear regression models. Results: After 12 weeks of GLP-1 RA therapy, the Control group showed significant reductions in SDNN, SDANN, RMSSD, pNN50, and lnHF, together with increases in lnLF and the lnLF/lnHF ratio, whereas no significant within-group changes in HRV indices were observed in the DAPA group. In unadjusted between-group analyses, several HRV parameters differed significantly between groups. After covariate adjustment, significant between-group differences remained for SDNN, SDANN, lnHF, and the lnLF/lnHF ratio. IPTW-weighted sensitivity analyses yielded consistent findings. In multivariable regression, baseline dapagliflozin use was most clearly associated with a more favorable change in SDNN. Conclusion: In patients with T2DM, dapagliflozin use was associated with a decline in HRV during GLP-1 RA therapy; these findings are hypothesis-generating and require confirmation in larger prospective studies.

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