Network and Pairwise Meta-Analysis of the Association Between Novel Hypoglycemic Agents and Atrial Fibrillation Risk in Patients With Type 2 Diabetes Mellitus.

OBJECTIVE

To evaluate the atrial fibrillation (AF) risk of sodium-glucose cotransporter-2 inhibitors (SGLT-2i), glucagonlike peptide-1 receptor agonists (GLP-1RA) and dipeptidyl peptidase-4 inhibitors (DPP-4i) in patients with Type 2 Diabetes Mellitus (T2DM) with network meta-analysis.

METHODS

Systematic literature searches were conducted of MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), Embase, and Clinical Trials.gov covering inception till January 31, 2026. Randomized control trials (RCTs) and cohort studies comparing SGLT-2i, GLP-1RA and DPP-4i in diabetes were selected. We performed a network meta-analysis to compare the three drugs indirectly. Results were reported as risk ration (RR) with corresponding 95% confidence interval (CI).

RESULTS

4 RCTs and 21 cohort studies involving 2,171,267 patients were included. Compared with GLP-1RA [RR with 95% CI: 0.86(0.79, 0.95), RR with 95% CI: 0.87(0.78, 0.97)] and DPP-4i[RR with 95% CI: 0.80(0.74, 0.87), RR with 95% CI: 0.81(0.74, 0.88)], SGLT-2i significantly reduced the risk of AF and new-onset AF. While there were no significant difference in the risk of AF recurrence among SGLT-2i, GLP-1RA, and DPP-4i[RR with 95% CI: 0.87(0.68, 1.12), RR with 95% CI: 0.80(0.61, 1.05), RR with 95% CI: 0.92(0.63, 1.33)]. There were also no significant difference in the risk of AF and new-onset AF between GLP-1RA and DPP-4i[RR with 95% CI: 0.93(0.84, 1.03), RR with 95% CI: 0.93(0.83, 1.04)].

CONCLUSIONS

The management of T2DM involves the prevention of subsequent cardiovascular complications. The results of this network meta-analysis indicate that SGLT2i is associated with a lower risk of AF in T2DM patients compared to GLP-1RA and DPP-4i. Sensitivity analysis further confirms that SGLT-2i significantly reduces the risk of AF recurrence statistically. These finding suggests that SGLT-2i should be considered as a preferred antidiabetic regimen for patients with T2DM at high risk of AF.