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.
背景：神经内分泌肿瘤（NENs）是一组异质性恶性肿瘤，主要包括神经内分泌瘤（NETs）和神经内分泌癌（NECs）两大亚型。胰高血糖素样肽-1受体激动剂（GLP-1Ra）在临床前研究中显示出良好效果，但其对NEN患者预后的影响尚未明确。 方法：通过TriNetX美国研究网络，我们筛选出同时患有NEN及糖尿病或肥胖症的成年患者。基于人口统计学特征、合并症、手术史及用药情况，进行1:1倾向评分匹配后，比较NEN诊断后接受GLP-1Ra治疗与未接受治疗患者的生存结局。 结果：在32,464例符合条件患者中，3,139例接受GLP-1Ra治疗，29,325例未接受治疗。倾向匹配后，两组各纳入3,043例基线特征均衡的患者。在长达15年的随访期间，GLP-1Ra使用组全因死亡356例（11.7%），非使用组753例（24.7%），绝对风险降低13.0%（p<0.001）。GLP-1Ra使用与显著改善的生存率相关（HR=0.56，95%CI=0.49–0.63，p<0.001）。无论是高分化肿瘤（HR=0.52）还是低分化肿瘤（HR=0.56）均显示出显著改善。在原发部位分析中，肺神经内分泌肿瘤获益最为显著（HR=0.42）。替尔泊肽与死亡率降低的关联性最强（HR=0.16），其次为司美格鲁肽（HR=0.27）和度拉糖肽（HR=0.52）。 结论：在这项大规模倾向匹配研究中，GLP-1Ra的使用与糖尿病或肥胖症NEN患者死亡率风险降低44.3%相关。观察到的显著获益提示GLP-1Ra可能在该患者群体中具有辅助治疗潜力。需要开展前瞻性临床试验以验证这些发现并探索其潜在机制。
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