Impact of glucagon-like peptide-1 receptor agonists on the incidence of atrial fibrillation

Table 1 Presenting detailed results

Title	Clinical trials	Observational studies	Controlled trials	Network meta-analyses
Antidiabetic agents and risk of atrial fibrillation/flutter: A comparative critical analysis with a focus on differences between SGLT2 inhibitors and GLP-1 receptor agonists		GLP-1RA therapy was not associated with a lower risk of incident AF in patients with T2DM (HR = 1.01, 95%CI: 0.86-1.1). GLP-1 RAs were associated with a surprising higher risk of new-onset AF (adjusted HR = 2.27, 95%CI: 1.49-3.47)	A total of 31 RCTs with a duration ≥ 12 weeks (enrolling 17966 patients and 15305 patients in GLP-1 RAs and comparator arms, respectively), treatment with GLP-1 RAs had no significant impact on the incidence of AF (OR = 0.87, 95%CI: 0.71-1.05, P = 0.15). In a further meta-analysis by the same research group that comprised 43 RCTs (63134 patients) with a duration ≥ 52 weeks, again GLP-1 RAs did not influence the risk of AF (OR = 0.94, 95%CI: 0.84-1.04) when compared to placebo or any other non-GLP-1 RA drug. Treatment with dula-glutide compared with placebo was not associated with a reduced incidence of atrial arrhythmias (combined AF and AFL: 5.6% vs 5%). GLP-1RA agonist tirzepatide compared with a placebo or active comparator did not have a signifi- cant effect on the risk for AF. Once-weekly injectable semaglutide compared to placebo reduced the risk of stroke (HR = 0.61, 95%CI: 0.38-0.99) while it also diminished the risk of new-onset AF by 29%	GLP-1 RAs were associated with a significant reduction in AF/AFL events compared with metformin (OR = 0.17, 95%CI: 0.04-0.61), SU (OR = 0.23, 95%CI: 0.07-0.73), insulin (OR = 0.20, 95%CI: 0.07-0.86), and non-SU compounds (OR = 0.18, 95%CI: 0.04-0.66). Thus, compared with other glucose-lowering agents, GLP-1 RAs could reduce the risk of AF/AFL in patients with diabetes. Compared with placebo, a significant lower AF/AFL risk was reported with both GLP-1 RAs (RR = 0.86, 95%CI: 0.76-0.97) and SGLT2 is (RR = 0.82, 95%CI: 0.68-0.99)
Association of glucagon-like peptide-1 receptor agonists with cardiac arrhythmias in patients with type 2 diabetes or obesity: A systematic review and meta-analysis of randomized controlled trials	Pooled data from all these trials indicated that GLP-1 RAs therapy had no significant association with the risk of incident AF (RR = 0.97, 95%CI: 0.83–1.12, P = 0.65). Dulaglutide displayed an increasing trend toward incident AF (RR = 1.40, 95%CI: 1.03–1.90, P = 0.03), while oral semaglutide displayed an inverse trend (RR = 0.43, 95%CI: 0.21–0.87, P = 0.02). Other GLP-1 RAs agents including albiglutide, exenatide, liraglutide, lixisenatide, and semaglutide had no significant effect on the risk of AF. GLP-1 RAs use did not significantly increase the incidence of AFL (RR = 0.83, 95%CI: 0.59–1.17, P = 0.96) compared to controls
Glucagon-like peptide-1 receptor agonist semaglutide reduces atrial fibrillation incidence: A systematic review and meta-analysis				Meta-analysis revealed that semaglutide reduces the risk of incident AF episodes by 42% (RR = 0.58, 95%CI: 0.40–0.85), with low heterogeneity across the included studies (I2 = 0%)
GLP-1 receptor agonists and myocardial metabolism in atrial fibrillation	Liraglutide, exenatide, dulaglutide, albiglutide, and semaglutide have all been shown to reduce major adverse cardiovascular events. Accordingly, recent guidelines have recommended the use of GLP-1 RAs for patients with T2DM at high risk of cardiovascular disease, especially heart failure and chronic kidney disease. However, treatment with GLP-1 RAs only has minimal benefit in reducing the risk of AF
Glucagon-like peptide-1 receptor agonists in the context of pathophysiology of diverse heart failure with preserved ejection fraction phenotypes: Potential benefits and mechanisms of action	GLP-1 RA therapy in diabetic mice reduced susceptibility to AF and duration of arrhythmia episodes. Meta-analysis, GLP-1 RAs significantly reduced AF events compared to metformin, sulfonylurea, insulin and non-sulfonylurea inpatients with T2DM and were associated with better outcomes compared toother medications. Two large meta-analyses of RCTs concerning T2DM did not show any significant risk for atrial and ventricular arrhythmias or sudden cardiac death associated with GLP-1 RAs
Role of Liraglutide Use in Patients With Heart Failure	Established a statistically significant risk of adverse outcomes in patients under the liraglutide group against the placebo group with [HR = 1.41, (95%CI: 1.01, 1.97), P = 0.043]

AF: Atrial fibrillation; AFL: Atrial flutter; GLP-1 Ras: Glucagon-like peptide-1 receptor agonists; HR: Hazard ratio; OR: Odds ratio; RCTs: Randomized clinical trials; RR: Relative risk; SGLT2: sodium-glucose co-transporter 2; SU: Sulfonylurea; T2DM: Type 2 diabetes mellitus.