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Review
. 2025 Aug 12;11(5):441-450.
doi: 10.1093/ehjcvp/pvaf040.

Prevention of atrial fibrillation with SGLT2 inhibitors across the spectrum of cardiovascular disorders: a meta-analysis of randomized controlled trials

Damiano Fedele  1   2 , Marcello Casuso Alvarez  1   3 , Angelo Maida  1   3 , Nicolò Vasumini  1   3 , Sara Amicone  1   2 , Lisa Canton  1   2 , Michele Di Leo  1   3 , Marco Basile  1   3 , Tommaso Manaresi  1   3 , Francesco Angeli  1   2 , Matteo Armillotta  1   2 , Luca Bergamaschi  1   2 , Carmine Pizzi  1   2
Affiliations
Review

Prevention of atrial fibrillation with SGLT2 inhibitors across the spectrum of cardiovascular disorders: a meta-analysis of randomized controlled trials

Damiano Fedele et al. Eur Heart J Cardiovasc Pharmacother. .

Abstract

Aims: The ability of sodium-glucose co-transporter 2 (SGLT2) inhibitors to prevent atrial fibrillation (AF) has been evaluated in various studies with conflicting results. This study aimed to determine whether SGLT2 inhibitors have a protective effect against AF depending on the baseline clinical condition in which the randomized controlled trials (RCTs) were conducted.

Methods and results: A trial-level meta-analysis was performed including 52 RCTs (112 031 patients) comparing SGLT2 inhibitors with placebo and reporting the number of patients who developed AF in each arm. Risk ratios (RRs) for AF development with 95% confidence intervals (95% CIs) were pooled using a random-effects model. Subgroup analyses were performed by classifying RCTs according to the inclusion criteria of each trial [diabetes, chronic kidney disease, heart failure with reduced ejection fraction (HFrEF), mildly reduced EF (HFmrEF), and preserved EF (HFpEF)]. Overall, SGLT2 inhibitors prevented AF (RR = 0.86, 95% CI 0.77-0.96). In the subgroup analysis, the AF-preventive ability of SGLT2 inhibitors was influenced by HF, being preserved in RCTs recruiting 9141 patients with HFrEF, but not in those recruiting 12 877 subjects with HFmrEF/HFpEF (P-value for group difference = 0.01). Meta-regression showed a reduced efficacy of SGLT2 inhibitors in preventing AF when more patients with hypertension or higher EF were enrolled (P < 0.01 for both).

Conclusion: Sodium-glucose co-transporter 2 inhibitors prevent AF. Their protective effect was confirmed in the HFrEF subgroup, but not in RCTs recruiting patients with HFmrEF/HFpEF, possibly indicating a different pathophysiology leading to AF among these conditions. However, given the limitations of a trial-level analysis, these findings are exploratory, pending confirmation from patient-level data.

Keywords: Atrial fibrillation; Diastolic dysfunction; Heart failure; Heart failure with preserved ejection fraction; Heart failure with reduced ejection fraction; SGLT2 inhibitors.

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Conflict of interest statement

Conflict of interest: none declared.

Figures

Figure 1
Figure 1
Flowchart of the meta-analysis.
Figure 2
Figure 2
Forest plot illustrating the atrial fibrillation preventive ability of sodium–glucose co-transporter 2 inhibitors. Pooled risk ratios calculated with a DerSimonian–Laird random-effects model. AF, atrial fibrillation; CI, confidence interval; SGLT2, sodium–glucose co-transporter 2.
Figure 3
Figure 3
Forest plot illustrating the association between sodium–glucose co-transporter 2 inhibitors and atrial fibrillation occurrences stratified considering the inclusion criteria of the trials. Pooled risk ratios calculated with a DerSimonian–Laird random-effects model. Subgroup analysis showing the protective effect of SGLT2 inhibitors against AF considering the inclusion criteria of the trials, including the presence of diabetes, chronic kidney disease, and heart failure stratified by clinical setting and ejection fraction. AF, atrial fibrillation; CI, confidence interval; EF, ejection fraction; HFmrEF, heart failure with mildly reduced ejection fraction; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; SGLT2, sodium–glucose co-transporter 2.
Figure 4
Figure 4
Bubble plot showing the relationship between the risk ratio of developing atrial fibrillation in the sodium–glucose co-transporter 2 inhibitors vs. placebo arms and mean the left ventricular ejection fraction of patients included in each trial. Each trial is represented as a circle, the diameter being representative of its weight. The red line shows the dependence of the natural logarithm of the risk ratio and a mean left ventricular ejection fraction with corresponding 95% confidence intervals (grey area). In this model, a risk ratio = 1 corresponds to mean left ventricular ejection fraction = 50.7%. However, this model is based on trial-level aggregate data and is not intended for individual-level predictions; it only illustrates a trend without implying a hard left ventricular ejection fraction threshold.
Figure 5
Figure 5
Risk factors for atrial fibrillation and systemic effects of sodium–glucose co-transporter 2 inhibitors. COPD, chronic obstructive pulmonary disease; HTN, hypertension; mrEF, mildly reduced ejection fraction; OSAS, obstructive apnoea syndrome; pEF, preserved ejection fraction; rEF, reduced ejection fraction; SGLT2, sodium–glucose co-transporter 2.
See this image and copyright information in PMC

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