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Network and Pairwise Meta-Analysis of the Association Between Novel Hypoglycemic Agents and Atrial Fibrillation Risk

Xuejiao Ye1, Qian Wu1, Linye Hou2

  • 1China Academy of Chinese Medical Sciences Guang'Anmen Hospital, Beijing, China.

Diabetes/Metabolism Research and Reviews
|July 15, 2026
PubMed
Abstract

Insights

Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) significantly lower atrial fibrillation (AF) risk in type 2 diabetes patients compared to GLP-1 receptor agonists (GLP-1RA) and DPP-4 inhibitors (DPP-4i). SGLT-2i also reduce AF recurrence, suggesting their preference for high-risk individuals.

Area of Science:

  • Cardiology
  • Endocrinology
  • Pharmacology

Background:

  • Type 2 Diabetes Mellitus (T2DM) management requires preventing cardiovascular complications.
  • Atrial fibrillation (AF) is a common complication in T2DM patients.
  • Comparative risk assessments of novel antidiabetic agents for AF are crucial.

Purpose of the Study:

  • To evaluate and compare the risk of atrial fibrillation (AF) associated with sodium-glucose cotransporter-2 inhibitors (SGLT-2i), glucagon-like peptide-1 receptor agonists (GLP-1RA), and dipeptidyl peptidase-4 inhibitors (DPP-4i) in patients with T2DM.
  • To conduct a network meta-analysis for indirect comparison of these drug classes regarding AF risk.

Main Methods:

  • Systematic literature searches of major databases (MEDLINE, CENTRAL, Embase, Clinical Trials.gov) up to January 31, 2026.
  • Inclusion of randomized controlled trials (RCTs) and cohort studies comparing SGLT-2i, GLP-1RA, and DPP-4i in diabetes patients.
  • Network meta-analysis to derive risk ratios (RR) and 95% confidence intervals (CI) for AF risk and recurrence.

Main Results:

  • Analysis included 4 RCTs and 21 cohort studies with 2,171,267 patients.
  • SGLT-2i significantly reduced the risk of AF and new-onset AF compared to GLP-1RA (RR 0.86 [0.79, 0.95]) and DPP-4i (RR 0.80 [0.74, 0.87]).
  • No significant differences in AF recurrence risk were found among the three drug classes.

Conclusions:

  • SGLT-2i demonstrate a lower risk of AF in T2DM patients compared to GLP-1RA and DPP-4i.
  • Sensitivity analysis confirmed SGLT-2i's significant reduction in AF recurrence risk.
  • SGLT-2i should be considered a preferred antidiabetic regimen for T2DM patients at high risk of AF.
Keywords:
DPP‐4 inhibitorsGLP‐1 receptor agonistSGLT‐2 inhibitorsatrial fibrillationnetwork meta‐analysistype 2 diabetes mellitus

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