Semaglutide and atrial fibrillation: a systematic review and meta-analysis

Introduction

Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, is widely prescribed for glycemic control and weight reduction. Given the well-established association between obesity and atrial fibrillation (AF) and new onset heart failure (HF), elucidating the potential effects of semaglutide on cardiac arrhythmogenesis is of increasing clinical interest. The aim was o investigate the association between semaglutide therapy and the incidence of new-onset atrial fibrillation, as well as HF incidence.

Methods

A systematic literature search of PubMed, Embase, and the Cochrane Library was performed to identify randomized controlled trials (RCTs) published between January 2010 and October 2024 that reported new-onset AF and new onset HF among patients treated with semaglutide. Both diabetic and non-diabetic populations were eligible for inclusion. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using the Mantel–Haenszel method under fixed- and random-effects models, as appropriate.

Results

Four RCTs, including three evaluating subcutaneous semaglutide and one assessing oral semaglutide, comprising a total of 9,116 patients, met the inclusion criteria. Across these trials, 215 cases of new-onset AF were documented. Overall, semaglutide use was associated with a significantly lower incidence of new-onset AF (pooled OR 0.75; 95% CI 0.57–0.98; p = 0.03), with low-to-moderate heterogeneity (I² = 32%). Subcutaneous semaglutide demonstrated a consistent and significant reduction in AF risk (OR 0.73; 95% CI 0.55–0.96; p = 0.02; I² = 30%). In contrast, oral semaglutide, evaluated in a single study, showed a wide and non-significant effect estimate (OR 5.02; 95% CI 0.24–104.88).

Regarding new-onset heart failure, pooled analysis across four studies suggested a potential risk reduction with semaglutide (OR 0.57; 95% CI 0.21–1.54; p = 0.27); however, this finding did not reach statistical significance and was characterized by substantial heterogeneity (I² = 91%; p < 0.00001).

Conclusion

is meta-analysis indicates that semaglutide use is associated with a reduced risk of new-onset atrial fibrillation, suggesting potential antiarrhythmic benefits beyond its established role in reducing major adverse cardiovascular events. Additional studies are warranted to validate these findings and to further clarify the arrhythmic and heart failure effects of oral semaglutide.For image description, please refer to the figure legend and surrounding text.