Observational studyFrontiers in endocrinology2026
Dapagliflozin associates with heart rate variability decline in T2DM patients on GLP-1 receptor agonist therapy: a prospective observational study.
Observational study in Frontiers in endocrinology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Abstract
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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