Do Incretin-Based Therapies Influence the Risk of Cholangiocarcinoma in Type 2 Diabetes Patients? Insights from a Systematic Review and Meta-Analysis.

IF 1.6 Q4 ONCOLOGY

Journal of Gastrointestinal Cancer Pub Date : 2025-10-11 DOI:10.1007/s12029-025-01330-9

Eric Ricardo Yonatan, Louis Fabio Jonathan Jusni, Steven Alvianto, Nicolas Daniel Widjanarko, Steven Yulius Usman, Virly Nanda Muzellina

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引用次数: 0

Abstract

Introduction: Incretin-based therapies, including glucagon-like peptide-1 receptor agonists (GLP-1RAs) and dipeptidyl peptidase-4 inhibitors (DPP-4Is), are widely used in the management of type 2 diabetes mellitus (T2DM). However, concerns have emerged regarding their potential association with an increased risk of cholangiocarcinoma (CCA), and current evidence remains inconclusive. This review aims to evaluate and clarify the association between incretin-based therapies and the risk of CCA in patients with T2DM.

Methods: This review followed PRISMA 2020 guidelines and was registered in PROSPERO (CRD42025641616). A comprehensive search was performed across PubMed, ProQuest, EBSCOhost, Wiley, and SAGE databases. Eligible observational studies reporting the association between incretin-based therapies and CCA were included. Study quality was assessed using the Newcastle-Ottawa Scale (NOS). Pooled hazard ratios (HRs) and risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using RevMan with a random-effects model.

Result: Four studies (three cohort and one case-control) were included. The pooled HRs showed no significant association between incretin-based therapies and CCA risk, with estimates of 1.07 (95% CI: 0.70-1.63) for GLP-1RAs and 1.05 (95% CI: 0.83-1.34) for DPP-4Is. Pooled RR analyses yielded similarly non-significant results. All included studies were assessed as having a low risk of bias according to the NOS.

Conclusion: Incretin-based therapies do not significantly increase the risk of CCA in T2DM patients. Within the limitations of the available observational evidence, these findings provide reassurance regarding their safety profile, while highlighting the need for ongoing pharmacovigilance and further large-scale studies to confirm these results.

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肠促胰岛素为基础的治疗是否影响2型糖尿病患者胆管癌的风险？来自系统回顾和元分析的见解。

以肠促胰岛素为基础的治疗，包括胰高血糖素样肽-1受体激动剂（GLP-1RAs）和二肽基肽酶-4抑制剂（DPP-4Is），广泛用于2型糖尿病（T2DM）的治疗。然而，人们担心它们与胆管癌（CCA）风险增加的潜在关联，目前的证据仍不确定。本综述旨在评估和阐明以肠促胰岛素为基础的治疗与T2DM患者CCA风险之间的关系。方法：本综述遵循PRISMA 2020指南，在PROSPERO注册（CRD42025641616）。在PubMed、ProQuest、EBSCOhost、Wiley和SAGE数据库中进行了全面的搜索。纳入了符合条件的观察性研究，报告了以肠促胰岛素为基础的治疗与CCA之间的关联。采用纽卡斯尔-渥太华量表（NOS）评估研究质量。采用RevMan随机效应模型计算合并风险比（hr）和95%置信区间（ci）的风险比（rr）。结果：共纳入4项研究（3项队列研究和1项病例对照研究）。综合hr显示，基于肠促胰岛素的治疗与CCA风险之间没有显著关联，GLP-1RAs的估计为1.07 (95% CI: 0.70-1.63)， DPP-4Is的估计为1.05 （95% CI: 0.83-1.34）。合并RR分析得出了类似的无显著性结果。根据nos，所有纳入的研究均被评估为低偏倚风险。结论：以肠促胰岛素为基础的治疗不会显著增加T2DM患者发生CCA的风险。在现有观察性证据的限制下，这些发现为其安全性提供了保证，同时强调需要持续的药物警戒和进一步的大规模研究来证实这些结果。

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

Journal of Gastrointestinal Cancer ONCOLOGY-

CiteScore

3.80

自引率

0.00%

发文量

121

期刊介绍： The Journal of Gastrointestinal Cancer is a multidisciplinary medium for the publication of novel research pertaining to cancers arising from the gastrointestinal tract.The journal is dedicated to the most rapid publication possible.The journal publishes papers in all relevant fields, emphasizing those studies that are helpful in understanding and treating cancers affecting the esophagus, stomach, liver, gallbladder and biliary tree, pancreas, small bowel, large bowel, rectum, and anus. In addition, the Journal of Gastrointestinal Cancer publishes basic and translational scientific information from studies providing insight into the etiology and progression of cancers affecting these organs. New insights are provided from diverse areas of research such as studies exploring pre-neoplastic states, risk factors, epidemiology, genetics, preclinical therapeutics, surgery, radiation therapy, novel medical therapeutics, clinical trials, and outcome studies.In addition to reports of original clinical and experimental studies, the journal also publishes: case reports, state-of-the-art reviews on topics of immediate interest or importance; invited articles analyzing particular areas of pancreatic research and knowledge; perspectives in which critical evaluation and conflicting opinions about current topics may be expressed; meeting highlights that summarize important points presented at recent meetings; abstracts of symposia and conferences; book reviews; hypotheses; Letters to the Editors; and other items of special interest, including:Complex Cases in GI Oncology: This is a new initiative to provide a forum to review and discuss the history and management of complex and involved gastrointestinal oncology cases. The format will be similar to a teaching case conference where a case vignette is presented and is followed by a series of questions and discussion points. A brief reference list supporting the points made in discussion would be expected.