Semaglutide Benefits Obesity-Related Heart Failure Equally in Patients With and Without Atrial Fibrillation | Research

The takeaway

In the STEP-HFpEF program (1,145 patients), semaglutide improved heart failure symptoms, weight, CRP, and NT-proBNP regardless of atrial fibrillation status — with even greater symptom improvements in those who had AF.

+11.5 vs +4.3 point KCCQ improvement
Semaglutide produced greater HF symptom improvements in patients with AF vs without AF

What the researchers found

Semaglutide 2.4 mg improved HFpEF outcomes regardless of AF status, with greater symptom improvements in AF patients (KCCQ-CSS +11.5 vs +4.3 points; P interaction=0.001).

Why it matters

AF and HFpEF often coexist, and clinicians need to know if treatments work across both conditions. This analysis confirms semaglutide benefits are not diminished by AF — and may actually be amplified in this higher-risk subgroup.

The numbers in context

Semaglutide 2.4 mg once weekly; STEP-HFpEF and STEP-HFpEF DM trials pooled; stratified by AF status.

How the study worked

Pre-specified secondary analysis of pooled data from STEP-HFpEF and STEP-HFpEF DM randomized trials. 1,145 patients with HFpEF and BMI ≥30, randomized 1:1 to semaglutide 2.4 mg vs placebo for 52 weeks, stratified by AF history.

Who was studied

Patients with obesity-related HFpEF with and without atrial fibrillation

What this study cannot tell us

Secondary/subgroup analysis — not powered for the AF subgroup comparison as a primary endpoint. AF history was investigator-reported, not adjudicated. AF types (paroxysmal, persistent, permanent) had varying sample sizes. 52-week follow-up may not capture long-term outcomes.

How to read the evidence

Strong evidence — secondary analysis of two well-designed, large randomized trials. Consistent results across endpoints increase confidence despite subgroup design.

When this study was published

Published in 2024. Part of the landmark STEP-HFpEF program establishing semaglutide's role in obesity-related heart failure.

The bigger picture

This analysis addresses a critical clinical question: should AF patients with obesity-related HFpEF receive semaglutide? The answer is a clear yes — and these patients may actually derive the most benefit, potentially changing how cardiologists approach this common comorbidity combination.

Questions still open

Does semaglutide reduce new-onset AF in obesity-related HFpEF patients?
Why does AF amplify semaglutide's symptom benefits — is it the weight loss, inflammation reduction, or hemodynamic effects?
Should semaglutide be considered as part of AF management in obese HFpEF patients?

Common questions

Can I take semaglutide if I have both heart failure and an irregular heartbeat?

Yes — this analysis of over 1,100 patients showed that semaglutide worked well regardless of whether patients had atrial fibrillation. In fact, patients with AF who took semaglutide had even greater improvements in heart failure symptoms than those without AF.

Why might semaglutide help more in patients with atrial fibrillation?

Patients with AF tend to have more advanced heart failure, more inflammation, and higher BMI. Semaglutide's multi-pronged benefits — weight loss, inflammation reduction, and improved cardiac function — may provide more room for improvement in these sicker patients.

Read the original research

Atrial Fibrillation and Semaglutide Effects in Obesity-Related Heart Failure With Preserved Ejection Fraction: STEP-HFpEF Program.

Journal of the American College of Cardiology, 84(17), 1603-1614

View on PubMed ↗Publisher’s paper ↗

Citation

Verma, Subodh; Butler, Javed; Borlaug, Barry A; Davies, Melanie J; Kitzman, Dalane W; Petrie, Mark C; Shah, Sanjiv J; Jensen, Thomas Jon; Rasmussen, Søren; Rönnbäck, Cecilia; Merkely, Bela; O'Keefe, Evan; Kosiborod, Mikhail N. (2024). Atrial Fibrillation and Semaglutide Effects in Obesity-Related Heart Failure With Preserved Ejection Fraction: STEP-HFpEF Program.. Journal of the American College of Cardiology, 84(17), 1603-1614. https://doi.org/10.1016/j.jacc.2024.08.023