Glucagon‐Like Peptide‐1 Agonists and the Incidence of Atrial Fibrillation in Obese Patients With Heart Failure With Preserved Ejection Fraction and No Diabetes

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Obese, non-diabetic heart failure with preserved ejection fraction (HFpEF) (n=940). Intervention: GLP-1 receptor agonists (semaglutide, liraglutide, or tirzepatide) vs. No GLP-1 RA therapy. Primary outcome: New onset atrial fibrillation (HR 0.86, 95% CI 0.53-1.39, p=0.543).

Q: What does this research mean for the field?

GLP-1 receptor agonist therapy is not associated with a reduced incidence of atrial fibrillation in obese, non-diabetic patients with heart failure with preserved ejection fraction, but is associated with reduced mortality. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Farah Rassam; Eduardo A. Lopez; Sarah Sass; Thitiphan Srikulmontri; Evan Isaacs; John Malin; Phuuwadith Wattanachayakul; Olayinka Afolabi-Brown

doi:10.1002/joa3.70455

September 22, 2026Journal of ArrhythmiaOpen Access

Glucagon‐Like Peptide‐1 Agonists and the Incidence of Atrial Fibrillation in Obese Patients With Heart Failure With Preserved Ejection Fraction and No Diabetes

View Full Paper

Ask AI

Bookmark

Share

Key result

GLP-1 RA therapy fails to reduce incident atrial fibrillation in obese patients with HFpEF.

HR 0.86
95% CI 0.53-1.39
P=0.543
n=940

Graphical abstract published by Journal of Arrhythmia — Graphical abstract · Published by Journal of Arrhythmia · CC BY-NC-ND

Why the study?

Does GLP-1 RA therapy reduce the incidence of new-onset atrial fibrillation in obese, non-diabetic patients with HFpEF?

Study Design

Type

Cohort (n=940)

Multicenter

Yes

Structured PICO

Does GLP-1 RA therapy reduce the incidence of new-onset atrial fibrillation in obese, non-diabetic patients with HFpEF?

P

Population

940 propensity-matched obese, non-diabetic adults with HFpEF, free of prior atrial fibrillation, followed for up to 5 years.

E

Exposure

Glucagon-like peptide-1 receptor agonist (GLP-1 RA) therapy (semaglutide, liraglutide, or tirzepatide) initiated between January 1, 2020 and December 31, 2024.

C

Comparator

No GLP-1 RA therapy (untreated patients with HFpEF and obesity).

O

Outcome

New onset atrial fibrillation (assessed 90-1825 days after index event).hard clinical

Main Result

Hazard Ratio: 0.86 (95% CI 0.53–1.39)

Absolute Event Rate: 7.8% vs 9%

p-value: p=0.543

In obese, non-diabetic patients with HFpEF, GLP-1 receptor agonists were associated with lower all-cause mortality but did not significantly reduce the incidence of new-onset atrial fibrillation.

Limitations

Retrospective EHR-based analysis
Residual confounding despite matching (e.g., imbalanced BMI)
Diagnosis misclassification, particularly under-detection of paroxysmal AF
Differing index dates introducing survivor and time-related bias
Lack of medication adherence, treatment duration, and detailed echocardiographic data
Residual confounding despite matching (e.g., BMI remained imbalanced)
Limited medication adherence, treatment duration, and detailed echocardiographic and laboratory data
Differing index dates may introduce survivor and time-related bias

Implication

No association with lower AF incidence in this cohort; leaves open whether GLP-1 RAs affect arrhythmia risk in obese HFpEF.

Abstract

Background Glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) reduce cardiovascular risk in obesity, but their effect on atrial fibrillation (AF) in heart failure with preserved ejection fraction (HFpEF) remains unclear. Methods We analyzed TriNetX data comparing obese, non‐diabetic HFpEF patients treated with GLP‐1 RAs ( n = 478) with untreated patients ( n = 6887). Propensity matching yielded 470 patients per cohort. Results GLP‐1 RA therapy was not associated with reduced AF incidence (HR 0.86; 95% CI, 0.53–1.39; p = 0.543) but was associated with lower mortality (HR 0.42; 95% CI, 0.23–0.75; p = 0.003). Conclusions GLP‐1 RAs may not reduce AF incidence in obese, HFpEF patients.

Discussion

No takes yet. Share an insight, caveat, or question.

Cite This Study

Rassam et al. (2026) conducted a cohort in Obese, non-diabetic heart failure with preserved ejection fraction (HFpEF) (n=940). GLP-1 receptor agonists (semaglutide, liraglutide, or tirzepatide) vs. No GLP-1 RA therapy was evaluated on New onset atrial fibrillation (HR 0.86, 95% CI 0.53-1.39, p=0.543). GLP-1 RA therapy was not associated with a reduced incidence of atrial fibrillation (HR 0.86, 95% CI 0.53-1.39, p=0.543) compared to no GLP-1 RA therapy in obese, non-diabetic patients with HFpEF.

synapsesocial.com/papers/6ab3619ee8129fc9b332b47f https://doi.org/10.1002/joa3.70455