Authors: Julie A. Gordon, Jon E. Folstad, Charley A. Hepfinger, Camille P. Robinette, Allison E. Strain, Anita A. Kelkar
Background: Heart failure with preserved ejection fraction (HFpEF) and heart failure with mildly reduced ejection fraction (HFmrEF) are highly prevalent among the aging population and contribute to significant morbidity and reduced quality of life. Unlike heart failure with reduced ejection fraction, guideline-directed medical therapy (GDMT) has not demonstrated clear mortality benefits in this population, and treatment primarily focuses on symptom management and comorbidity control. Obesity is a major modifiable risk factor in HFpEF and HFmrEF that contributes to worsening symptoms and increased hospitalizations. Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonists, including semaglutide and tirzepatide, have demonstrated effective weight loss and clinical benefits in this population. However, their impact on heart failure related outcomes has not yet been evaluated at the Salisbury VA Health Care System (SVAHCS). This project aims to evaluate if semaglutide and tirzepatide lead to clinical improvement in Veterans with HFpEF or HFmrEF and how prescribing patterns influence outcomes at the SVAHCS.
Methods: This quality improvement project was a retrospective chart review of Veterans with HFpEF or HFmrEF prescribed semaglutide or tirzepatide for at least six months between January 2022 and July 2025 at the SVAHCS. Collected variables included demographics, duration and dose of therapy, medication titration schedule (standard vs. slow), prescribing discipline (Pharmacy, Endocrinology, Primary Care), and number of titration-related clinic visits attended during therapy. The primary outcome was percentage change in body weight. Secondary outcomes included changes in B-type natriuretic peptide (BNP), ejection fraction (EF), HgbA1C, LDL, blood pressure medication and loop diuretic requirements, and symptoms of heart failure. Prescribing discipline, titration method, and follow-‑up frequency were evaluated.
Results: A total of 266 patients were identified using the Weight Management Patient Report Dashboard. After chart review was performed to confirm eligibility, 52 patients were included, most of whom had HFpEF (90%) and obesity (96%). Patients who remained on the agent for at least 12 months experienced an average weight loss of 6.26% (p-value <0.001). Improvements were observed in weight, LDL, HgbA1C, BNP, and EF, although sample sizes varied. Compared to other disciplines, pharmacist-managed patients attended the highest number of clinic visits during therapy titration and exhibited the greatest percentage of weight loss (p-value=0.24) as well as the largest reduction in BNP (p-value=0.93). However, these differences were not statistically significant. Although most patients (81%) underwent slow titration, those receiving standard titration reached maximum dose more rapidly and achieved greater weight loss (p-value=0.15). Across the cohort, 29% had an antihypertensive medication reduced or discontinued, and patients achieving ≥5% weight loss were more likely to require loop diuretic dose reduction, suggesting improved volume status and symptom control.
Conclusion: Semaglutide and tirzepatide were associated with meaningful weight loss and favorable cardiometabolic trends in Veterans with HFpEF or HFmrEF. Differences in outcomes across prescribing disciplines highlight the importance of follow‑up frequency, access to care, and titration intensity, with pharmacist‑managed care demonstrating the strongest improvements.
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