Glucagon-like peptide-1 receptor agonists and risk of pancreaticobiliary cancers in patients with type 2 diabetes: a nationwide cohort study

IF 5.8 2区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetes & metabolism Pub Date : 2026-07-01 Epub Date: 2026-06-25 DOI:10.1016/j.diabet.2026.101776

Byeong Geun Song, Tae-Se Kim, Bong Seong Kim, Kyungdo Han, Byung-Hoon Min

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引用次数: 0

Abstract

Aim

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have demonstrated substantial metabolic benefits, but their association with pancreaticobiliary cancer risk remains unclear. We investigated the association between GLP-1RA use and pancreaticobiliary cancer incidence in patients with type 2 diabetes (T2D).

Methods

This population-based cohort study used Korean National Health Insurance Service data from 2011 to 2023. We identified 51,780 patients with T2D receiving metformin plus sulfonylurea who initiated either GLP-1RA (n=24,052) or dipeptidyl peptidase-4 inhibitor (DPP-4i, n=27,728). The primary outcomes were incident pancreatic cancer, bile duct cancer, gallbladder cancer, and composite pancreaticobiliary cancer. Hazard ratios (HRs) were estimated using Cox proportional hazards models adjusted for demographics, comorbidities, and previous diabetes medications.

Results

During 208,992 person-years of follow-up (mean 4.0 years), 321 pancreaticobiliary cancers occurred. GLP-1RA use was associated with a significantly lower risk of pancreatic cancer (adjusted HR 0.668, 95% CI 0.476-0.939). Similar trends were observed for bile duct cancer (adjusted HR 0.649, 95% CI 0.375-1.124), gallbladder cancer (adjusted HR 0.418, 95% CI 0.171-1.019), and composite pancreaticobiliary cancer (adjusted HR 0.681, 95% CI 0.515-0.901). These associations remained consistent in a propensity score–matched analysis and after excluding patients with baseline pancreaticobiliary disease.

Conclusion

In this large cohort study, GLP-1RA use was associated with reduced pancreatic cancer risk compared with DPP-4i use among patients with T2D. Similar trends were observed for other pancreaticobiliary cancers. These findings suggest potential protective effects that warrant confirmation in longer-term studies.

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胰高血糖素样肽-1受体激动剂与2型糖尿病患者胰胆癌的风险：一项全国性队列研究

目的:。胰高血糖素样肽-1受体激动剂（GLP-1RAs）已显示出实质性的代谢益处，但其与胰胆癌风险的关系尚不清楚。我们研究了GLP-1RA的使用与2型糖尿病（T2D）患者胰胆癌发病率之间的关系。方法:。-这项基于人群的队列研究使用了2011年至2023年的韩国国民健康保险服务数据。我们确定了51780例接受二甲双胍加磺脲治疗的t2dm患者，他们开始GLP-1RA （n=24,052）或二肽基肽酶-4抑制剂（DPP-4i, n=27,728）。主要结局为胰腺癌、胆管癌、胆囊癌和复合胰胆管癌。使用Cox比例风险模型对人口统计学、合并症和既往糖尿病药物进行调整，估计风险比（hr）。结果:。在208,992人年的随访期间（平均4.0年），发生了321例胰胆管癌。GLP-1RA的使用与胰腺癌风险显著降低相关（调整后HR 0.668, 95% CI 0.476-0.939）。胆管癌（调整HR 0.649, 95% CI 0.375-1.124）、胆囊癌（调整HR 0.418, 95% CI 0.171-1.019）和复合胰胆管癌（调整HR 0.681, 95% CI 0.515-0.901）也有类似的趋势。在倾向评分匹配分析和排除基线胰胆管疾病患者后，这些关联保持一致。结论:。在这项大型队列研究中，与使用DPP-4i相比，在T2D患者中使用GLP-1RA与降低胰腺癌风险相关。其他胰胆管癌也有类似的趋势。这些发现表明潜在的保护作用值得长期研究证实。

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

Diabetes & metabolism 医学-内分泌学与代谢

CiteScore

12.00

自引率

4.20%

发文量

审稿时长

13 days

期刊介绍： A high quality scientific journal with an international readership Official publication of the SFD, Diabetes & Metabolism, publishes high-quality papers by leading teams, forming a close link between hospital and research units. Diabetes & Metabolism is published in English language and is indexed in all major databases with its impact factor constantly progressing. Diabetes & Metabolism contains original articles, short reports and comprehensive reviews.