Semaglutide Improves Heart Structure in Obesity-Related Heart Failure | Research

The takeaway

In patients with obesity-related heart failure with preserved ejection fraction, semaglutide 2.4 mg weekly reduced left atrial enlargement and improved diastolic filling compared to placebo over 52 weeks.

-6.13 mL left atrial volume
Semaglutide significantly attenuated left atrial enlargement compared to placebo over 52 weeks (p=0.0013), a key marker of disease progression in HFpEF

What the researchers found

Semaglutide 2.4 mg weekly significantly reduced left atrial volume progression (-6.13 mL vs placebo, p=0.0013), right ventricular enlargement (RV end-diastolic area -1.99 cm², p=0.016), and improved diastolic filling parameters (E-wave velocity -5.63 cm/s, p=0.0037; E/A ratio -0.14, p=0.0075) over 52 weeks.

Why it matters

HFpEF is the most common form of heart failure and has had very few effective treatments. This study provides the first evidence that semaglutide may be genuinely disease-modifying in obesity-related HFpEF — not just improving symptoms through weight loss, but actually reversing harmful structural changes in the heart.

The numbers in context

Semaglutide dose: 2.4 mg once weekly. Study population: patients with obesity-related HFpEF.

How the study worked

Prespecified echocardiography substudy of pooled STEP-HFpEF and STEP-HFpEF DM randomized controlled trials. 491 of 1,145 participants had echocardiograms at baseline and 52 weeks. Treatment effects assessed using analysis of covariance stratified by trial and BMI, adjusted for baseline values.

Who was studied

Patients with obesity-related heart failure with preserved ejection fraction

What this study cannot tell us

Only 43% of trial participants had echocardiographic data at both timepoints, raising questions about selection bias. The study was not independently powered for the echocardiographic endpoints. Effects on LV dimensions, mass, and systolic function were not significant. Longer follow-up needed to determine if structural improvements translate to reduced cardiovascular events.

How to read the evidence

Strong evidence from a prespecified substudy of two large, well-conducted randomized controlled trials (STEP-HFpEF Program) published in the Journal of the American College of Cardiology.

When this study was published

Published in 2024, representing the latest evidence on semaglutide's cardiac structural effects from the landmark STEP-HFpEF trial program.

The bigger picture

Heart failure with preserved ejection fraction affects millions and has been notoriously difficult to treat because the heart's pumping function appears normal but filling is impaired. The finding that semaglutide can reverse adverse cardiac remodeling positions GLP-1 receptor agonists as potentially transformative for cardiovascular medicine, not just diabetes and obesity treatment.

Questions still open

Do the cardiac structural improvements persist after semaglutide is discontinued, or do they reverse with weight regain?
Would semaglutide show similar cardiac benefits in HFpEF patients who are not obese?
Do these echocardiographic improvements translate into fewer hospitalizations and better long-term survival?

Common questions

What is HFpEF and why is it so hard to treat?

HFpEF (heart failure with preserved ejection fraction) means the heart squeezes normally but doesn't relax and fill properly. It's the most common type of heart failure, especially in older adults with obesity, but unlike other heart failure types, very few medications have been proven to help. That's why semaglutide's benefits here are particularly significant.

Is semaglutide helping the heart directly or just through weight loss?

Both, likely. Greater weight loss was associated with greater reduction in left atrial volume, suggesting weight loss plays a role. However, improvements in diastolic filling (E-wave velocity, E/A ratio) and right ventricular size were not linked to the degree of weight loss, suggesting semaglutide may also have direct cardiac benefits independent of weight reduction.

Read the original research

Effect of Semaglutide on Cardiac Structure and Function in Patients With Obesity-Related Heart Failure.

Journal of the American College of Cardiology, 84(17), 1587-1602

View on PubMed ↗Publisher’s paper ↗

Citation

Solomon, Scott D; Ostrominski, John W; Wang, Xiaowen; Shah, Sanjiv J; Borlaug, Barry A; Butler, Javed; Davies, Melanie J; Kitzman, Dalane W; Verma, Subodh; Abildstrøm, Steen Z; Nygaard Einfeldt, Mette; Rasmussen, Søren; Abhayaratna, Walter P; Ahmed, Fozia Z; Ben-Gal, Tuvia; Chopra, Vijay; Ito, Hiroshi; Merkely, Bela; Núñez, Julio; Senni, Michele; van der Meer, Peter; Wolf, Dennis; Petrie, Mark C; Kosiborod, Mikhail N. (2024). Effect of Semaglutide on Cardiac Structure and Function in Patients With Obesity-Related Heart Failure.. Journal of the American College of Cardiology, 84(17), 1587-1602. https://doi.org/10.1016/j.jacc.2024.08.021