Semaglutide Improves Health, Reduces Depression and Anxiety in Obese Heart Failure Patients Over One Year

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.

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.

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.

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.

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.