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Review
. 2025 Jul 27;14(15):5306.
doi: 10.3390/jcm14155306.

SGLT2 Inhibitors and the Risk of Arrhythmias in Heart Failure: A Network Meta-Analysis

Suchith Boodgere Suresh  1 , Aishwarya Prasad  1 , Muhammad Furqan Ubaid  1 , Saad Farooq  1 , Adrija Hajra  2 , Vikash Jaiswal  3 , Aaqib Malik  4 , Gregg C Fonarow  5 , Dhrubajyoti Bandyopadhyay  6
Affiliations
Review

SGLT2 Inhibitors and the Risk of Arrhythmias in Heart Failure: A Network Meta-Analysis

Suchith Boodgere Suresh et al. J Clin Med. .

Abstract

Background/Objectives: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have revolutionized heart failure (HF) therapies and are an essential component of guideline-directed medical therapy (GDMT); however, their significance in arrhythmia prevention is still uncertain. This meta-analysis evaluates the benefits of SGLT2i on arrhythmias in HF. Methods: A comprehensive examination was performed with PubMed, ScienceDirect, PLOS One, Cochrane, Google Scholar, and ClinicalTrials.gov from January 2014 to March 2025, complying with PRISMA guidelines. Randomized controlled trials (RCTs) comparing SGLT2i with placebo were incorporated. Primary results included ventricular arrhythmias (VA), sudden cardiac death (SCD), atrial arrhythmias, and conduction disorders. Subgroup analyses investigated the effects on arrhythmias in HF with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). Results: A total of 11 RCTs involving 23,701 patients, 11,848 on SGLT2i (mean age: 68.26 ± 10 yrs, 53.5% males) and 11,853 on placebo (mean age: 67.91 ± 10 yrs, 53% males), were analyzed with a mean follow-up of 2.71 yrs. No significant differences were reported between SGLT2i and placebo for VA [relative risk (RR): 1.02, 95% confidence interval (CI): 0.83-1.25], I2 =0%), atrial arrhythmias (RR: 0.92 [CI: 0.67-1.27], I2 = 65.3%), or conduction disorders (RR:1.22 [CI: 0.86-1.73], I2 = 10.4%). Notably, significant reductions in risk of SCD (RR: 0.68 [CI: 0.49-0.93], I2 = 0%) and in the risk of atrial arrhythmias in HFrEF (RR: 0.66 [CI: 0.49-0.89], I2 = 10.3%) were witnessed, although no such reduction was seen in HFpEF (RR: 1.14 [CI: 0.94-1.40], I2 = 33.8%). Conclusions: SGLT2i do not reduce overall arrhythmia or conduction disorder risk in HF but significantly reduce the risk of SCD and atrial arrhythmias in HFrEF patients. These results highlight potential arrhythmia prevention benefits in HFrEF, warranting further targeted studies.

Keywords: arrhythmia; atrial fibrillation; sodium-glucose cotransporter-2 inhibitor; sudden cardiac death.

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Conflict of interest statement

Fonarow reports consulting for Abbott Amgen, AstraZeneca Bayer, Boehinger Ingelheim, Cytokinetics, Eli Lilly, Johnson & Johnson, Medtronic Merck, Novartis and Pfizer. The other authors have nothing to disclose.

Figures

Figure 1
Figure 1
Ref. [6]: Meta-analysis of 11 randomized controlled trials demonstrates that SGLT2 inhibitors and the risk of arrhythmias, with subgroup analyses across heart failure phenotypes. The illustration highlights underlying mechanisms on ion channel modulation and structural remodeling. Created in BioRender. B suresh, S. (2025) https://BioRender.com/xvkacqi (26 July 2025).
Figure 2
Figure 2
PRISMA flowchart.
Figure 3
Figure 3
Risk of sudden cardiac death (SCD) with SGLT2 inhibitors: Forest plots display risk ratios for SCD overall, stratified by heart failure phenotypes and specific SGLT2 inhibitors (Dapagliflozin, Empagliflozin, Canagliflozin, Sotagliflozin) versus placebo. The network diagram illustrates direct and indirect comparisons among these treatments. The heatmap shows the relative ranking of each treatment based on netmeta analysis.
Figure 4
Figure 4
Risk of ventricular arrhythmia (VA) with SGLT2 inhibitors: Forest plots display risk ratios for VA overall, stratified by heart failure phenotypes and specific SGLT2 inhibitors (Dapagliflozin, Empagliflozin, Sotagliflozin) versus placebo. The network diagram illustrates direct and indirect comparisons among these treatments. The heatmap shows the relative ranking of each treatment based on netmeta analysis.
Figure 5
Figure 5
Risk of atrial arrhythmia (AA) with SGLT2 inhibitors: Forest plots display risk ratios for AA overall, stratified by heart failure phenotypes and specific SGLT2 inhibitors (Dapagliflozin, Empagliflozin, Sotagliflozin) versus placebo. The network diagram illustrates direct and indirect comparisons among these treatments. The heatmap shows the relative ranking of each treatment based on netmeta analysis.
Figure 6
Figure 6
Risk of bradyarrhythmia and conduction disorder with SGLT2 inhibitors: Forest plots display risk ratios for bradyarrhythmia and conduction disorder overall, stratified by heart failure phenotypes and specific SGLT2 inhibitors (Dapagliflozin, Empagliflozin, Sotagliflozin) versus placebo. The network diagram illustrates direct and indirect comparisons among these treatments. The heatmap shows the relative ranking of each treatment based on netmeta analysis.
Figure 7
Figure 7
Electrophysiological mechanisms of SGLT2i [6].
See this image and copyright information in PMC

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