Semaglutide provides cardio-protection in anthracycline-treated non-hodgkin lymphoma: a propensity-matched real-world study
A Briasoulis, C Filippatos, P Kostakou, N Tepetes, I Boutsikos, D Fotiou, M Gavriatopoulou, M A Dimopoulos, E TerposAbstract
Introduction
Anthracycline-induced cardiotoxicity remains a primary driver of morbidity and mortality in Non-Hodgkin Lymphoma (NHL) survivors. While semaglutide has demonstrated cardioprotective effects in non-cancer populations, its impact on patients undergoing high-risk chemotherapy is unknown.
Methods
We identified adults with NHL receiving anthracycline-based regimens within the TriNetX database. Patients were stratified into two cohorts: those with concurrent semaglutide exposure and a control group without exposure. Propensity score matching (PSM) was utilized to balance baseline demographics, disease characteristics, medications and cardiovascular/metabolic risk factors.
Results
After matching, two well-balanced cohorts of 994 patients were formed. The median follow-up was 584 days for the semaglutide cohort and 730 days for the control group. Semaglutide was associated with significant benefits in overall survival (HR=0.20, 95%CI: 0.15-0.26; p<0.001). For cardiovascular outcomes, semaglutide demonstrated significant protection across: 3P-MACE: HR=0.47 (95%CI: 0.33-0.67, p<0.001), Acute Myocardial Infarction: HR=0.41 (95% CI: 0.26-0.64, p<0.001), Heart Failure: HR-0.60 (95%CI: 0.44-0.82, p=0.001) and Atrial Fibrillation/Flutter: HR=0.42 (95%CI: 0.28-0.62, p<0.001). Furthermore, a significant reduction in Acute Kidney Injury was observed (HR 0.29; 95% CI: 0.21–0.4, p<0.001) and a trend for reduced rates of all-cause hospitalizations (HR=0.74, 95%CI: 0.49-1.12, p=0.156). No significant differences were observed in the risk of stroke (HR=0.77, p = 0.344).
Conclusion
In this large-scale, real-world analysis, semaglutide was associated with a significant primary prevention of major cardiac and renal complications in NHL patients receiving anthracyclines. These findings suggest that GLP-1RAs may possess potent cardioprotective and potentially pleiotropic oncological benefits that warrant prospective validation in cardio-oncology trials.