Journal Article Epublish 2 citations
PubMed: 40361517 DOI: 10.3390/cancers17091593
Survival Benefits of GLP-1 Receptor Agonists in Patients with Neuroendocrine Neoplasms: A Large-Scale Propensity-Matched Cohort Study.
Cancers (Basel) 17(9)
Authors: Manal S Fawzy, Awwad Alenezy, Jessan A Jishu, Issa Khan, Ahmad Dessouky, Ahmed Abdelmaksoud, Kristen E Limbach, Eman A Toraih
Affiliations
- Center for Health Research, Northern Border University, Arar 73213, Saudi Arabia.
- Department of Family and Community Medicine, Faculty of Medicine, Northern Border University, Arar 91431, Saudi Arabia.
- School of Medicine, Tulane University, 1430 Tulane Ave. New Orleans, LA 70112, USA.
- SUNY Upstate Medical University, New York, NY 13210, USA.
- Faculty of Medicine, Suez Canal University, Ismailia 41522, Egypt.
- Department of Internal Medicine, University of California, Riverside, CA 92521, USA.
- Department of Surgery, School of Medicine, Tulane University, 1430 Tulane Ave. New Orleans, LA 70112, USA.
- Department of Cardiovascular Perfusion, Interprofessional Research, College of Health Professions, SUNY Upstate Medical University, New York, NY 13210, USA.
- Genetics Unit, Department of Histology and Cell Biology, Faculty of Medicine, Suez Canal University, Ismailia 41522, Egypt.
Abstract
Background: Neuroendocrine neoplasms (NENs) represent a heterogeneous group of malignancies that consist of two major subtypes: neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs). Glucagon-like peptide-1 receptor agonists (GLP-1Ra) have demonstrated favorable results in preclinical studies, but their impact on NEN outcomes remains unexplored. Methods: Using the TriNetX US Research Network, we identified adult patients with NEN and either diabetes or obesity. After 1:1 propensity score matching based on demographics, comorbidities, procedures, and medication use, we compared survival outcomes between patients who received GLP-1Ra after NEN diagnosis and those who did not. Results: Among 32,464 eligible patients, 3139 received GLP-1Ra and 29,325 did not. After propensity matching, each cohort included 3043 patients with well-balanced baseline characteristics. During follow-up periods extending up to 15 years, all-cause mortality occurred in 356 (11.7%) GLP-1Ra users versus 753 (24.7%) non-users, representing a 13.0% absolute risk reduction (p < 0.001). GLP-1Ra use was associated with significantly improved survival (HR = 0.56, 95%CI = 0.49-0.63, p < 0.001). Both well-differentiated (HR = 0.52) and poorly differentiated tumors (HR = 0.56) showed significant improvement. Among primary sites, lung NENs demonstrated the most pronounced benefit (HR = 0.42). Tirzepatide showed the strongest association with reduced mortality (HR = 0.16), followed by semaglutide (HR = 0.27) and dulaglutide (HR = 0.52). Results: In this large propensity-matched study, GLP-1Ra use was associated with a 44.3% reduction in mortality risk among NEN patients with diabetes or obesity. The magnitude of the observed benefit suggests a potential role for GLP-1Ra as adjunctive therapy in this patient population. Prospective clinical trials are warranted to confirm these findings and explore underlying mechanisms.
MeSH
Diabetes Mellitus, Glucagon-Like Peptide 1, Pancreatic Neoplasms, Mortality, Glucagon-Like Peptide-1 Receptor, Neoplasms, Cohort Studies, Lung Neoplasms, Obesity, Neuroendocrine Tumors, Carcinoma, Neuroendocrine, Semaglutide