Fawzy Manal S, Alenezy Awwad, Jishu Jessan A, Khan Issa, Dessouky Ahmad, Abdelmaksoud Ahmed, Limbach Kristen E, Toraih Eman A
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.
Cancers (Basel). 2025 May 7;17(9):1593. doi: 10.3390/cancers17091593.
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. 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. 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 ( < 0.001). GLP-1Ra use was associated with significantly improved survival (HR = 0.56, 95%CI = 0.49-0.63, < 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). 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.
神经内分泌肿瘤（NENs）是一组异质性恶性肿瘤，主要由两个主要亚型组成：神经内分泌瘤（NETs）和神经内分泌癌（NECs）。胰高血糖素样肽-1受体激动剂（GLP-1Ra）在临床前研究中已显示出良好的效果，但其对NENs预后的影响仍未得到探索。利用TriNetX美国研究网络，我们确定了患有NENs且患有糖尿病或肥胖症的成年患者。在根据人口统计学、合并症、手术和药物使用情况进行1:1倾向评分匹配后，我们比较了NENs诊断后接受GLP-1Ra治疗的患者与未接受该治疗的患者的生存结果。在32464名符合条件的患者中，3139名接受了GLP-1Ra治疗，29325名未接受。倾向匹配后，每个队列包括3043名基线特征均衡的患者。在长达15年的随访期内，356名（11.7%）使用GLP-1Ra的患者发生全因死亡，而未使用者为753名（24.7%），绝对风险降低了13.0%（<0.001）。使用GLP-1Ra与生存率显著提高相关（HR = 0.56，95%CI = 0.49 - 0.63，<0.001）。高分化肿瘤（HR = 0.52）和低分化肿瘤（HR = 0.56）均显示出显著改善。在原发部位中，肺NENs显示出最显著的益处（HR = 0.42）。替尔泊肽与死亡率降低的关联最强（HR = 0.16），其次是司美格鲁肽（HR = 0.27）和度拉鲁肽（HR = 0.52）。在这项大型倾向匹配研究中，对于患有糖尿病或肥胖症的NEN患者，使用GLP-1Ra与死亡风险降低44.3%相关。观察到的益处程度表明GLP-1Ra在该患者群体中作为辅助治疗具有潜在作用。有必要进行前瞻性临床试验以证实这些发现并探索潜在机制。
