Effect of GLP-1 receptor agonists and co-agonists on atrial fibrillation risk in overweight or obesity: systematic review and meta-analysis of randomized controlled trials.

Summary

Across 24 randomized trials including 40,694 participants with overweight/obesity, GLP-1 receptor agonists and co-agonists reduced incident atrial fibrillation by 18% versus placebo. The benefit appears at least partially independent of the magnitude of weight loss, suggesting direct antiarrhythmic or cardiometabolic mechanisms.

Key Findings

• Meta-analysis of 24 RCTs (n=40,694) showed an 18% relative reduction in incident AF with GLP-1RAs/co-agonists vs placebo (RR 0.82; 95% CI 0.70–0.96).
• The cardioprotective effect appears at least partly independent of weight-loss magnitude.
• Results support antiarrhythmic and cardiometabolic benefits of GLP-1–based therapies in overweight/obese populations.

Clinical Implications

In patients with overweight/obesity at elevated AF risk (e.g., prior ablation, high atrial ectopy, structural heart disease), consider GLP-1–based therapies for both weight management and potential AF risk reduction alongside standard preventive strategies.

Limitations

• Heterogeneity in AF ascertainment and follow-up across trials; AF often a secondary outcome
• Limited data to fully disentangle weight-loss–independent mechanisms

Future Directions

Prospective RCTs with AF incidence as a primary endpoint and mechanistic biomarker substudies (electrophysiology, atrial remodeling, inflammation) to determine causal pathways and responder phenotypes.