Long-term effects of SGLT2 inhibitors on arrhythmias: a systematic review and meta-analysis

AimsSodium-glucose co-transporter 2 (SGLT2) inhibitors are novel oral hypoglycemic agents strongly endorsed in the treatment guidelines for heart failure due to their cardioprotective benefits. However, their specific impact of SGLT2 inhibitors on arrhythmias incompletely understood. This systematic...

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Main Authors: Peipei Li, Weiwei Chen, Rui Chen, Hanmo Zhang, Zhixi Yu, Hongyu Yan, Beibei Du, Ping Yang
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-07-01
Series:Frontiers in Pharmacology
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Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2025.1558367/full
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author Peipei Li
Weiwei Chen
Rui Chen
Hanmo Zhang
Zhixi Yu
Hongyu Yan
Beibei Du
Ping Yang
author_facet Peipei Li
Weiwei Chen
Rui Chen
Hanmo Zhang
Zhixi Yu
Hongyu Yan
Beibei Du
Ping Yang
author_sort Peipei Li
collection DOAJ
description AimsSodium-glucose co-transporter 2 (SGLT2) inhibitors are novel oral hypoglycemic agents strongly endorsed in the treatment guidelines for heart failure due to their cardioprotective benefits. However, their specific impact of SGLT2 inhibitors on arrhythmias incompletely understood. This systematic review and meta-analysis aimed to comprehensively evaluate the long-term effects of SGLT2 inhibitors on various arrhythmia types.MethodsWe systematically searched PubMed, Embase, Web of Science, and ClinicalTrials.gov from database inception to 30 June 2024, to identify randomized controlled clinical trials (RCTs) with a follow-up duration of at least 52 weeks. The primary outcome of the meta-analysis was atrial fibrillation (AF) or atrial flutter (AFL), and the secondary outcomes included ventricular tachycardia (VT), ventricular fibrillation (VF), and sinus bradycardia. The pooled risk ratios (RRs) with 95% confidence intervals (CIs) were used to estimate the incidence of arrhythmias.ResultsThirty-nine RCTs involving 107,770 participants were included. The results of meta-analysis revealed that patients treated with SGLT2 inhibitors had a reduced risk of AF/AFL compared with placebo (RR 0.86; 95%CI, 0.77–0.95; I2 = 0%; P = 0.003). There was no significant difference in the risk of AF/AFL between the high-dose SGLT2 inhibitors group and the low-dose SGLT2 inhibitors group (RR 0.78; 95%CI, 0.60–1.02; I2 = 0%; P = 0.07), although a decreasing trend in the high-dose group was noted. Similarly, no significant differences were found for VT (RR 0.99; 95%CI, 0.81–1.22; I2 = 0%; P = 0.96), VF (RR 1.06; 95%CI, 0.73–1.54; I2 = 0%; P = 0.75) or sinus bradycardia (RR 1.12; 95%CI, 0.57–2.18; I2 = 0%; P = 0.74) between the SGLT2 inhibitors and placebo groups.ConclusionSGLT2 inhibitors significantly reduce the risk of AF/AFL but have no notable impact on the risk of VT, VF, and sinus bradycardia. Additionally, different doses of SGLT2 inhibitors did not statistically influence AF/AFL incidence.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/home, identifier PROSPERO:CRD42022371089
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spelling doaj-art-6ab70cc74e6442e08352eea75133b2d92025-08-20T02:37:38ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-07-011610.3389/fphar.2025.15583671558367Long-term effects of SGLT2 inhibitors on arrhythmias: a systematic review and meta-analysisPeipei Li0Weiwei Chen1Rui Chen2Hanmo Zhang3Zhixi Yu4Hongyu Yan5Beibei Du6Ping Yang7Department of Cardiology, Jilin Provincial Cardiovascular Research Institute, China-Japan Union Hospital of Jilin University, Changchun, ChinaDepartment of Cardiology, Jilin Provincial Cardiovascular Research Institute, China-Japan Union Hospital of Jilin University, Changchun, ChinaCardiovascular Hospital, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, ChinaSchool of Medicine, Nankai University, Tianjin, ChinaDepartment of Cardiology, Jilin Provincial Cardiovascular Research Institute, China-Japan Union Hospital of Jilin University, Changchun, ChinaDepartment of Cardiology, Jilin Provincial Cardiovascular Research Institute, China-Japan Union Hospital of Jilin University, Changchun, ChinaDepartment of Cardiology, Jilin Provincial Cardiovascular Research Institute, China-Japan Union Hospital of Jilin University, Changchun, ChinaDepartment of Cardiology, Jilin Provincial Cardiovascular Research Institute, China-Japan Union Hospital of Jilin University, Changchun, ChinaAimsSodium-glucose co-transporter 2 (SGLT2) inhibitors are novel oral hypoglycemic agents strongly endorsed in the treatment guidelines for heart failure due to their cardioprotective benefits. However, their specific impact of SGLT2 inhibitors on arrhythmias incompletely understood. This systematic review and meta-analysis aimed to comprehensively evaluate the long-term effects of SGLT2 inhibitors on various arrhythmia types.MethodsWe systematically searched PubMed, Embase, Web of Science, and ClinicalTrials.gov from database inception to 30 June 2024, to identify randomized controlled clinical trials (RCTs) with a follow-up duration of at least 52 weeks. The primary outcome of the meta-analysis was atrial fibrillation (AF) or atrial flutter (AFL), and the secondary outcomes included ventricular tachycardia (VT), ventricular fibrillation (VF), and sinus bradycardia. The pooled risk ratios (RRs) with 95% confidence intervals (CIs) were used to estimate the incidence of arrhythmias.ResultsThirty-nine RCTs involving 107,770 participants were included. The results of meta-analysis revealed that patients treated with SGLT2 inhibitors had a reduced risk of AF/AFL compared with placebo (RR 0.86; 95%CI, 0.77–0.95; I2 = 0%; P = 0.003). There was no significant difference in the risk of AF/AFL between the high-dose SGLT2 inhibitors group and the low-dose SGLT2 inhibitors group (RR 0.78; 95%CI, 0.60–1.02; I2 = 0%; P = 0.07), although a decreasing trend in the high-dose group was noted. Similarly, no significant differences were found for VT (RR 0.99; 95%CI, 0.81–1.22; I2 = 0%; P = 0.96), VF (RR 1.06; 95%CI, 0.73–1.54; I2 = 0%; P = 0.75) or sinus bradycardia (RR 1.12; 95%CI, 0.57–2.18; I2 = 0%; P = 0.74) between the SGLT2 inhibitors and placebo groups.ConclusionSGLT2 inhibitors significantly reduce the risk of AF/AFL but have no notable impact on the risk of VT, VF, and sinus bradycardia. Additionally, different doses of SGLT2 inhibitors did not statistically influence AF/AFL incidence.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/home, identifier PROSPERO:CRD42022371089https://www.frontiersin.org/articles/10.3389/fphar.2025.1558367/fullsodium-glucose co-transporter 2 inhibitorsarrhythmiaatrial fibrillationatrial fluttermeta-analysis
spellingShingle Peipei Li
Weiwei Chen
Rui Chen
Hanmo Zhang
Zhixi Yu
Hongyu Yan
Beibei Du
Ping Yang
Long-term effects of SGLT2 inhibitors on arrhythmias: a systematic review and meta-analysis
Frontiers in Pharmacology
sodium-glucose co-transporter 2 inhibitors
arrhythmia
atrial fibrillation
atrial flutter
meta-analysis
title Long-term effects of SGLT2 inhibitors on arrhythmias: a systematic review and meta-analysis
title_full Long-term effects of SGLT2 inhibitors on arrhythmias: a systematic review and meta-analysis
title_fullStr Long-term effects of SGLT2 inhibitors on arrhythmias: a systematic review and meta-analysis
title_full_unstemmed Long-term effects of SGLT2 inhibitors on arrhythmias: a systematic review and meta-analysis
title_short Long-term effects of SGLT2 inhibitors on arrhythmias: a systematic review and meta-analysis
title_sort long term effects of sglt2 inhibitors on arrhythmias a systematic review and meta analysis
topic sodium-glucose co-transporter 2 inhibitors
arrhythmia
atrial fibrillation
atrial flutter
meta-analysis
url https://www.frontiersin.org/articles/10.3389/fphar.2025.1558367/full
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