SGLT2 inhibitors and dual SGLT1/2 inhibitors for the prevention of atrial fibrillation: A systematic review and network meta-analysis of randomized controlled trials

A BSTRACT Objectives: This study aimed to compare the relative efficacy of individual SGLT2 inhibitors and dual SGLT1/2 inhibitors in preventing atrial fibrillation (AF). Materials and Methods: This network meta-analysis adhered to the Preferred Reporting Items for Systematic reviews and Meta-analyses 2020 guidelines. A comprehensive literature search was conducted in PubMed, the Cochrane Library, and ClinicalTrials.gov up to September 1, 2025. Data analyses were performed using MetaInsight v6.4.2. Odds ratios (ORs) with 95% credible intervals were estimated using Bayesian models, and surface under the cumulative ranking curve (SUCRA) values were calculated to rank treatment effects. Sensitivity, subgroup analyses, and network meta-regression analyses were also conducted. Results: Sixty-two randomized controlled trials, including 117,623 participants, were analyzed. Among six SGLT inhibitors evaluated, dapagliflozin significantly reduced the risk of AF compared with placebo (OR 0.706, 95% CrI: 0.511–0.965; SUCRA: 85.10), ranking highest among all interventions. Sensitivity analysis, subgroup, and meta-regression showed consistent results, with no significant modifying effects of diabetes, heart failure, chronic kidney disease, baseline AF status, risk of bias, follow-up duration, age, sample size, and gender on the outcome. Conclusion: Among SGLT2 and dual SGLT1/2 inhibitors, dapagliflozin demonstrated the most consistent association with reduced odds of AF, independent of baseline comorbidities. These findings suggest a potential class effect favoring dapagliflozin for AF prevention.