Comparison of Sodium–Glucose Cotransporter 2 Inhibitors and Glucagon-like Peptide Receptor Agonists for Atrial Fibrillation in Type 2 Diabetes Mellitus: Systematic Review With Network Meta-analysis of Randomized Controlled Trials

ABSTRACT: Atrial fibrillation (AF) is a major public health concern with a rising prevalence. Although sodium-glucose cotransporter 2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) have shown the respective favorable effects on reducing the occurrence of AF/atrial flutter (AFL), comparative protective AF/AFL effects between above 2 novel antidiabetic agents remain unavailable. Thus, we aimed to evaluate the comparative efficacy of SGLT2is and GLP-1RAs in reducing the risk of AF/AFL in patients with type 2 diabetes and estimate relative rankings of interventions. PubMed, Embase, and ClinicalTrials.gov were searched up to December 1, 2020. All available randomized controlled trials comparing SGLT2is and GLP-1RAs with one another or placebo in patients with type 2 diabetes were included. Pooled results were shown as risk ratios (RRs) with 95% confidence intervals (CIs). We used a frequentist network meta-analysis to evaluate the outcomes of interests. Thirty-six randomized controlled trials including 85,701 participants with type 2 diabetes were identified. Compared with placebo, both SGLT2is (RR: 0.82, 95% CI, 0.68-0.99) and GLP-1RAs (RR: 0.86, 95% CI, 0.76-0.97; RR long-acting ones: 0.87, 95% CI, 0.76-0.99; RR short-acting ones: 0.72, 95% CI, 0.45-1.14) significantly reduced AF/AFL risk. No significant difference between SGLT2is and GLP-1RAs was noted (RR: 0.95, 95% CI, 0.76-1.2). Compared with placebo, results from the analysis showed an RR of 0.72 (95% CI, 0.45-1.14) for short-acting GLP-1RAs and 0.87 (95% CI, 0.76-0.99) for long-acting GLP-1RAs in reducing the risk of AF/AFL. Compared with placebo, both SGLT2is and GLP-1RAs possessed favorable effects on reducing the risk of AF/AFL. However, no difference was observed when comparisons were made between them. In addition, long-acting ones may confer a more pronounced AF/AFL reduction benefit compared with placebo.