In 122 obese heart failure patients, one year of semaglutide treatment significantly reduced BMI, improved heart failure symptoms, and decreased both anxiety and depression scores.
Depression scores halved (6→3)HADS depression scores dropped 50% over one year of semaglutide in obese heart failure patients, alongside significant improvements in anxiety, cardiac symptoms, and weight
What the researchers found
Over one year, semaglutide treatment in 122 obese heart failure patients produced: BMI decrease of -2.23 kg/m² (95% CI: -2.71 to -1.75; p significant). HADS anxiety scores dropped from 5 to 3 points (p=0.037). HADS depression scores dropped from 6 to 3 points (p significant). KCCQ overall summary scores improved significantly. NYHA functional class and NT-proBNP levels also improved. Benefits were consistent across subgroups: HFrEF vs. HFpEF, BMI 30-35 vs. ≥35, ischemic vs. non-ischemic cardiomyopathy, and diabetic vs. non-diabetic patients.
Why it matters
Heart failure patients with obesity face a compounded burden: the physical limitations of heart failure worsen with excess weight, and both conditions are associated with depression and anxiety. Semaglutide's ability to simultaneously improve weight, cardiac function, and mental health in these patients is remarkable — it addresses the physical and psychological dimensions of a disease that profoundly impacts quality of life. This is especially important because depression in heart failure is associated with worse outcomes and is often undertreated.
How the study worked
This was a retrospective analysis of 122 consecutive obese heart failure patients treated with semaglutide between January 2019 and August 2023. Primary endpoints were changes in BMI, Hospital Anxiety and Depression Scale (HADS) scores, and Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OSS) from baseline to one year. Secondary endpoints included NYHA functional class changes and NT-proBNP levels. Subgroup analyses were performed by ejection fraction, BMI category, cardiomyopathy etiology, and diabetes status.
What this study cannot tell us
This is a retrospective observational study without a control group, so improvements cannot be definitively attributed to semaglutide versus other factors (regression to mean, concurrent treatments, lifestyle changes). The sample size of 122 is moderate. Self-reported mood scales (HADS) are subjective. The specific semaglutide dose and titration protocols are not detailed. Some data appears truncated in the abstract (incomplete confidence intervals), limiting precise interpretation of certain results.
How to read the evidence
This is a retrospective observational study of 122 patients without a control group. While it provides real-world evidence with a meaningful sample size and one-year follow-up, the lack of randomization and control means the observed improvements cannot be causally attributed to semaglutide alone.
When this study was published
Published in 2025, this study uses patient data from 2019-2023 and represents current real-world experience with semaglutide in heart failure patients.
The bigger picture
The SELECT and STEP-HFpEF trials established semaglutide's cardiovascular benefits, but mood outcomes have received less attention. This study adds evidence that GLP-1 agonist peptides may have meaningful neuropsychiatric benefits in cardiometabolic patients. Whether this reflects direct brain effects of GLP-1 receptor activation, indirect benefits of weight loss and improved physical function, or both, the clinical impact is significant. As depression is increasingly recognized as a cardiovascular risk factor, treatments that address both simultaneously are especially valuable.
Questions still open
- Are semaglutide's mood improvements driven primarily by weight loss and improved physical function, or does GLP-1 receptor activation in the brain contribute directly to antidepressant effects?
- Would a randomized controlled trial confirm these mood benefits in heart failure patients, and how would they compare to standard antidepressant therapy?
Common questions
Can a weight loss drug really help with depression in heart failure patients?
Does semaglutide work equally well for different types of heart failure?
Read the original research
Impact of semaglutide on health outcomes and mood in obese heart failure patients: a retrospective analysis.
Clinical research in cardiology : official journal of the German Cardiac Society
Citation
Balata, Mahmoud; Sugiura, Atsushi; Hassan, Marwa; Rady, Mohamed; Christoph, Marian; Ibrahim, Karim; Becher, Marc Ulrich; Youssef, Akram. (2025). Impact of semaglutide on health outcomes and mood in obese heart failure patients: a retrospective analysis.. Clinical research in cardiology : official journal of the German Cardiac Society. https://doi.org/10.1007/s00392-025-02694-5