Meta-Analysis Evaluating the Risk of Atrial Fibrillation With Newer Antidiabetics Across the Cardiovascular and Renal Outcome Trials

Abstract

Objective: Patients with type 2 diabetes mellitus (T2DM) experience a significantly increased risk for atrial fibrillation (AF) compared to unaffected subjects. The latter confers to increased risk for heart failure, all-cause and cardiovascular mortality. Notably, even patients with sufficient glycemic control feature an increased risk for AF. Thus, it seems to be of interest whether antidiabetic treatment can affect the risk for AF among patients with T2DM. Design and method: We searched PubMed from its inception to 2 October 2020. We sought to determine the risk of AF with the use of newer antidiabetics, namely dipeptidyl-peptidase 4 (DPP-4) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose co-transporter-2 (SGLT-2) inhibitors, extracting corresponding data from the published cardiovascular and renal outcome trials. We assessed the risk for AF with each drug class separately. Results: We pooled data from 4 trials with DPP-4 inhibitors versus placebo or active comparator in a total of 34,884 patients, from 7 trials with GLP-1RAs versus placebo in a total of 55,943 patients and from 7 trials with SGLT-2 inhibitors versus placebo in a total of 55,966 patients. Risk of bias is considered as low across all selected studies. DPP-4 inhibitor treatment resulted in a non-significant decrease in the risk for AF, equal to 7% (RR = 0.93, 95% CI; 0.75 to 1.16, I2 = 1%). Similarly, GLP-1RA treatment produced a non-significant decrease in the risk for AF, equal to 12% (RR = 0.88, 95% CI; 0.76 to 1.03, I2 = 29%). Notably, SGLT-2 inhibitor treatment significantly decreased the risk for AF 19% (RR = 0.81, 95% CI; 0.69 to 0.95, I2 = 0%). Conclusions: Collectively, newer antidiabetics do not confer an increased risk for AF among patients with T2DM, while, SGLT-2 inhibitors seem to be protective, providing an additional cardiovascular benefit, besides the well-established ones.

Can glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors help in mitigating the risk of atrial fibrillation in patients with diabetes?

“…metformin) and sodium-glucose cotransporter-2 inhibitors (SGLT-2i) have shown promise in the mitigation of this heightened risk of AF in patients with diabetes [3]. However, limited existing evidence suggests that other antidiabetic agents such as glucagon-like peptide-1 receptor agonists (GLP-1 RA) and dipeptidyl peptidase-4 inhibitors (DPP-4i) may not offer similar benefits in overall risk reduction of AF in diabetes [4]. Therefore, we sought to study the association between AF-related adverse events (AEs) and GLP-1 RA, DPP-4i using the Food and Drug Administration's Adverse Event Reporting System (FAERS) database.…”