Divergent Risks of Endocrine and Nonendocrine Malignancies in GLP-1 Receptor Agonist Users: A Propensity-Matched Real-World Analysis of Over 140 000 Patients

IF 4.4 3区医学 Q2 ENDOCRINOLOGY & METABOLISM

Endocrine Practice Pub Date : 2026-10-01 Epub Date: 2026-05-15 DOI:10.1016/j.eprac.2026.05.010

Cheng-Hsien Hung BSc, Fu-Shun Yen MD, Jing-Yang Huang PhD, James Cheng-Chung Wei MD, PhD

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引用次数: 0

Abstract

Objective

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely used for type 2 diabetes mellitus (T2DM). The long-term impact on cancer risk remains uncertain. This study aimed to evaluate the association between GLP-1 RA and the risk of cancer, including site-specific malignancies.

Methods

This retrospective cohort study utilized the TriNetX database. Adults with T2DM between 2015 and 2023 were identified. After 1:1 propensity score matching, 144 410 GLP-1 RA users were compared with nonusers. Primary outcomes were all-cause mortality and incident malignant neoplasms. Secondary outcomes included site-specific cancers.

Results

GLP-1 RA use was associated with lower all-cause mortality (hazard ratio [HR] 0.693) and a reduced overall incidence of cancer (HR 0.905). Regarding nonendocrine malignancies, significant risk reductions were observed for digestive cancers (HR 0.710) and respiratory cancers (HR 0.691), as well as for other sites including oral, female genital, and central nervous system cancers. In contrast, GLP-1 RA was linked to an increased risk of thyroid gland cancer (HR 1.411). Active-comparator analyses against dipeptidyl peptidase-4 inhibitor and sodium-glucose co-transporter 2 inhibitor yielded broadly consistent findings. Landmark analyses at 3 years showed attenuation of the thyroid cancer signal to nonsignificance, suggesting surveillance bias rather than a true carcinogenic effect.

Conclusion

This real-world analysis demonstrates divergent oncologic risks associated with GLP-1 RA use, while the therapy offers potential protective effects against nonendocrine malignancies (particularly digestive and respiratory). The initially elevated thyroid cancer risk was no longer significant at 3 years, suggesting surveillance bias. These findings support the overall oncologic safety of GLP-1 RA in T2DM management, while warranting further long-term studies to confirm these associations.

查看原文本刊更多论文

GLP-1受体激动剂使用者的内分泌和非内分泌恶性肿瘤的不同风险：超过140,000例患者的倾向匹配的现实世界分析

目的：胰高血糖素样肽-1受体激动剂（GLP-1 RA）广泛用于2型糖尿病（T2DM）。对癌症风险的长期影响仍不确定。本研究旨在评估GLP-1RA与癌症（包括部位特异性恶性肿瘤）风险之间的关系。方法：采用TriNetX数据库进行回顾性队列研究。确定2015年至2023年间患有2型糖尿病的成年人。在1:1的倾向评分匹配后，将144,410名GLP-1RA使用者与非使用者进行比较。主要结局为全因死亡率和恶性肿瘤发生率。次要结局包括部位特异性癌症。结果：GLP-1RA的使用与较低的全因死亡率（HR 0.693）和降低的总体癌症发病率（HR 0.905）相关。对于非内分泌恶性肿瘤，消化道癌症（HR 0.710）和呼吸系统癌症（HR 0.691）以及其他部位包括口腔、女性生殖器和中枢神经系统癌症的风险显著降低。相反，GLP-1RA与甲状腺癌风险增加有关（HR 1.411）。针对DPP-4i和SGLT2i的活性比较分析得出了大致一致的结果。3年的里程碑分析显示甲状腺癌信号衰减到不显著，提示监测偏差而不是真正的致癌作用。结论：这一现实世界的分析表明，GLP-1RA的使用与不同的肿瘤风险相关，而该疗法对非内分泌恶性肿瘤（特别是消化和呼吸系统肿瘤）具有潜在的保护作用。最初升高的甲状腺癌风险在3年后不再显著，提示监测偏差。这些发现支持GLP-1 RA在T2DM治疗中的总体肿瘤学安全性，同时需要进一步的长期研究来证实这些关联。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Endocrine Practice ENDOCRINOLOGY & METABOLISM-

CiteScore

7.60

自引率

2.40%

发文量

546

审稿时长

41 days

期刊介绍： Endocrine Practice (ISSN: 1530-891X), a peer-reviewed journal published twelve times a year, is the official journal of the American Association of Clinical Endocrinologists (AACE). The primary mission of Endocrine Practice is to enhance the health care of patients with endocrine diseases through continuing education of practicing endocrinologists.