Low-Dose Semaglutide Shows Promise in Improving Heart Failure Symptoms Independent of Weight Loss

Recent research presented at the American Heart Association's Basic Cardiovascular Sciences Scientific Sessions (BCVS 2025) highlights the potential for low doses of the injectable weight-loss drug semaglutide to enhance symptoms of a challenging type of heart failure, known as heart failure with preserved ejection fraction (HFpEF). Notably, these benefits occurred without significant weight reduction, suggesting a direct positive effect of semaglutide on the heart and blood vessels.

HFpEF is characterized by the heart's inability to relax properly, leading to impaired filling of the left ventricle and insufficient blood flow. This condition is increasingly common, especially among older adults and individuals with high blood pressure, diabetes, or obesity, and it accounts for roughly half of all heart failure cases.

Current treatments for HFpEF are limited, and while previous studies, such as the STEP-HFpEF trial in 2023, indicated that semaglutide could reduce symptoms and improve quality of life in obese patients, it remained unclear whether these benefits stemmed primarily from weight loss. The new animal studies aimed to explore this question further.

In the study, researchers used genetically obese rats and pigs subjected to high blood pressure-inducing diets to closely mimic human HFpEF. They administered low doses of semaglutide twice weekly over a period of 12 to 16 weeks. This dosing was carefully selected to minimize weight loss, allowing scientists to examine the drug's direct effects on cardiac and vascular function.

Results showed significant improvements despite no notable weight loss. Key findings included a 58% increase in exercise capacity, a 61% enhancement in ventricular relaxation and filling, a 37% decrease in cardiac scarring, and reductions in fat accumulation within the heart and liver by 65% and 42%, respectively. Additionally, blood vessel flexibility improved by 52%. This suggests that semaglutide can positively influence heart structure and function through mechanisms other than weight reduction.

Elbatreek, the study's lead researcher, expressed excitement about these findings, emphasizing that the multiple direct effects on cardiovascular health are promising for developing new treatments targeting HFpEF, especially for patients unable or unwilling to undergo significant weight loss.

Furthermore, since lower doses of semaglutide tend to cause fewer side effects such as gastrointestinal discomfort, this approach may broaden the therapeutic options for a wider patient population. However, it is important to note that animal study results do not always translate directly to humans, and further clinical research is needed to confirm these benefits.

Cardiologists and researchers highlight that these insights could eventually lead to more effective, targeted therapies for HFpEF, a condition that currently lacks specific and highly effective treatment options. The ongoing investigation into semaglutide’s cardiovascular effects continues to shed light on its potential beyond weight management.