A reduction in atrial fibrillation incidence in obese patients on SGLT2 Inhibitors: a scoping review

Background

Obesity markedly increases atrial fibrillation (AF) risk through atrial stretch, systemic inflammation, and excess epicardial adipose tissue, leading to pathological electrophysiological remodelling. Sodium–glucose cotransporter-2 inhibitors (SGLT2i) exert broad cardiometabolic benefits that may reduce the incidence of AF in obese patients; however, evidence in obese populations remains limited.

Aim

To conduct a scoping review to map the incidence of AF in obese patients using SGLT2i and to critically evaluate their cardiac mechanisms from recent clinical evidence.

Methodology:

A scoping review was conducted following the PRISMA-ScR (Figure 1) and JBI frameworks to identify relevant studies involving adults (≥18 years) that reported incident AF and provided mean BMI data in obese patients receiving any SGLT2i compared with placebo, no treatment, or other antidiabetic therapy. Obesity was defined using population-specific BMI thresholds: ≥30 kg/m² for Western populations and ≥25 kg/m² for Asian populations, consistent with WHO guidelines. Eligible randomised controlled trials, observational studies, and meta-analyses published in English from 2015–2025 were retrieved from Medline, Embase, Cochrane Library and Web of Science. Two reviewers independently screened, extracted, and narratively synthesised data.

Results

Eighteen studies, including large-scale randomised trials, cardiovascular outcome studies, and pooled analyses covering over 300,000 participants, indicated a consistent reduction in new-onset AF among patients treated with SGLT2i , most notably with dapagliflozin. Across diverse clinical populations, event rates suggested approximately a 14–31% lower AF incidence compared with controls in obese populations (Table 1), with a median follow-up of 1 to 6 years. Mechanistic studies showed these agents lowered arrhythmia risk by shortening action potential duration, reducing intracellular calcium overload, improving mitochondrial function, and mitigating systemic inflammation. Also, SGLT2i reduced epicardial adipose tissue volume, potentially leading to favourable atrial remodelling through reduced local paracrine inflammation. Notably, these benefits appeared consistent across all BMI categories; however, direct evidence on AF outcomes in exclusively obese cohorts remains limited, with only a few studies stratifying outcomes by BMI.

Conclusion

SGLT2i , particularly dapagliflozin, appear to lower incident AF and improve atrial substrate remodelling through ionic, metabolic and anti-inflammatory pathways. However, current evidence is largely based on studies in which the mean participant BMI was within the obese range, rather than from cohorts exclusively comprising obese individuals. Therefore, further research is warranted to clarify their specific benefit in exclusively obese populations.Data extraction tablePRISMA Flow Diagram