Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely used for glycemic control and cardiovascular risk reduction in type 2 diabetes mellitus (T2DM), but their effects on cardiac autonomic function remain clinically relevant. A prospective observational study published in Frontiers in Endocrinology evaluated whether baseline dapagliflozin use was associated with less decline in heart rate variability (HRV) during 12 weeks of GLP-1 RA therapy. 

The analysis included 45 patients with T2DM who initiated GLP-1 RA therapy and underwent 24-hour ambulatory electrocardiographic monitoring before treatment and after 12 weeks. Participants were stratified into a dapagliflozin-naïve control group (n=22) and a dapagliflozin-exposed group (n=23). Between-group differences were further evaluated using analysis of covariance (ANCOVA), inverse probability of treatment weighting (IPTW), and multivariable linear regression models. 

Findings

• After 12 weeks of GLP-1 RA therapy, the control group showed significant reductions in SDNN, SDANN, RMSSD, pNN50, and lnHF, with increases in lnLF and the lnLF/lnHF ratio.
• No significant within-group HRV changes were observed in the dapagliflozin-exposed group after 12 weeks.
• After covariate adjustment, significant between-group differences remained for SDNN, SDANN, lnHF, and the lnLF/lnHF ratio.
• Inverse probability of treatment weighting sensitivity analyses yielded consistent findings.
• In multivariable regression analysis, baseline dapagliflozin use was most strongly associated with a more favorable change in SDNN. 

Baseline dapagliflozin use was associated with less decline in heart rate variability parameters during GLP-1 RA therapy in patients with T2DM. The findings suggest potential differences in cardiac autonomic effects according to baseline SGLT2 inhibitor use, although confirmation in larger prospective studies is needed.