Effect of sodium-glucose cotransporter-2 inhibitors on electrocardiographic markers of ventricular repolarization: A systematic review and meta-analysis

BACKGROUND: Sodium-glucose cotransporter-2 (SGLT2) inhibitors reduce sudden cardiac death and ventricular arrhythmias in cardiovascular outcome trials, but the electrophysiological mechanism remains unclear. Surface electrocardiographic (ECG) markers of repolarization dispersion may reflect myocardial electrical stability and provide mechanistic insight. AIM: To assess the impact of SGLT2 inhibitors on electrocardiographic markers of ventricular repolarization dispersion and conduction, and to evaluate whether these changes are consistent with improved ventricular electrical stability. METHODS: We conducted a systematic review and meta-analysis of studies reporting ECG parameters before and after SGLT2 inhibitors and studies comparing SGLT2 inhibitors with other treatments. Searches were performed from database inception through June 2025 across Scopus, Web of Science, PubMed, Scilit, and Google Scholar. Random-effects inverse-variance models using restricted maximum likelihood with Hartung-Knapp adjustment were applied. Prespecified subgroup analyses were performed by follow-up duration. RESULTS: Seventeen studies involving 5022 patients were included. In pre-post analyses, SGLT2 inhibitors significantly reduced QTc (MD -4.9 ms), Tp-e (MD -6.12 ms), P dispersion (MD -3.28 ms), and QTc dispersion (MD -1.36 ms), while R-R interval, PR interval, and QRS duration remained unchanged. Improvements in Tp-e-related indices and QRS-T angle were more pronounced at 6 months. In two-arm comparisons, SGLT2 inhibitors significantly shortened QT interval, QTc, Tp-e, Tp-e/QT, and Tp-e/QTc compared with controls. CONCLUSION: SGLT2 inhibitors reduce ECG markers of ventricular repolarization dispersion without affecting heart rate or conduction intervals, indicating improved ventricular electrical homogeneity.