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GLP-1 Receptor Agonists or Dual GLP-1/GIP Receptor Agonists vs. SGLT2 Inhibitors in Patients with Atrial Fibrillation

Faizan Ahmed1, Najam Gohar2, Madeeha Shafqat3

  • 1Department of Internal Medicine, Hackensack Meridian Health, Jersey Shore University Medical Center, Neptune, NJ 07753, USA.

Journal of Clinical Medicine
|July 15, 2026
PubMed

Insights

Incretin-based therapies, including GLP-1 receptor agonists, significantly reduced mortality and hospitalizations in patients with atrial fibrillation and heart failure with preserved ejection fraction compared to SGLT2 inhibitors.

Area of Science:

  • Cardiology
  • Pharmacology
  • Metabolic Diseases

Background:

  • Atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF) commonly coexist, increasing patient morbidity and mortality.
  • Cardiovascular benefits of sodium-glucose cotransporter-2 inhibitors (SGLT2i) and incretin-based therapies (GLP-1 receptor agonists, dual GIP/GLP-1 agonists) are known, but their comparative effectiveness in AF/HFpEF is unclear.

Purpose of the Study:

  • To compare the effectiveness of incretin-based therapies versus SGLT2 inhibitors in patients with concomitant atrial fibrillation and HFpEF.
  • To evaluate outcomes including all-cause mortality, hospitalizations, and major adverse cardiovascular events.

Main Methods:

  • Retrospective, propensity score-matched cohort study using the TriNetX Global Collaborative Network.
  • Included adults with AF/atrial flutter and HFpEF initiating incretin-based therapy or SGLT2i.
  • 1:1 matching based on demographics, comorbidities, and baseline medications; co-primary outcomes assessed at 1 year.

Main Results:

  • Incretin-based therapy was associated with lower 1-year all-cause mortality (5.3% vs. 7.3%) and fewer inpatient visits (30.0% vs. 37.4%) compared to SGLT2i.
  • Reduced risk of major adverse cardiovascular events (MACE), acute kidney injury, myocardial infarction, catheter ablation, and electrical cardioversion observed with incretin-based therapy.
  • No significant difference in emergency department visits, ischemic stroke, or transient ischemic attack between groups.

Conclusions:

  • Incretin-based therapies demonstrated superior outcomes in reducing mortality and hospitalizations compared to SGLT2i in patients with AF and HFpEF.
  • Findings suggest potential benefits of incretin-based therapy in this high-risk population.
  • Prospective comparative trials are warranted to confirm these observational findings.

Keywords:
GLP-1 receptor agonistsGLP-1/GIP receptor agonistsHFpEFSGLT2 inhibitorsatrial fibrillationcardiovascular outcomesincretin-based therapy

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