在接受检查点抑制剂治疗的患者中，二甲双胍的使用、免疫介导的结肠炎和总生存率之间的关系

IF 7.6 1区医学 Q1 ONCOLOGY

European Journal of Cancer Pub Date : 2025-04-02 DOI:10.1016/j.ejca.2025.115405

Malek Shatila , Carolina Colli Cruz , Linfeng Lu , Kian Abdul-baki , Elliot Baerman , Kei Takigawa , Andres Urias Rivera , Irene Jeong-Ah Lee , Sean Ngo , Gabriel Sperling , Abdullah Sagar Aleem , Raakhi Menon , Andrew Sullivan , Varun Vemulapalli , Cristina Natha , Tanvi Gupta , Ayesha Khan , Nitish Mittal , Garrett Coleman , Hamza Salim , Yinghong Wang

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引用次数: 0

摘要

二甲双胍常用于治疗2型糖尿病。它主要调节肝脏和结肠的葡萄糖代谢，但最近的研究表明它具有抗炎作用，特别是在结肠炎中。有研究表明，二甲双胍可以增强免疫检查点抑制（ICI）治疗癌症的疗效。我们的研究旨在探讨二甲双胍对ICI疗效和结肠炎风险的影响。方法：本研究为单中心回顾性分析，纳入2010年1月至2022年12月在某三级癌症中心连续接受ICI治疗并发展为免疫介导性结肠炎（IMC）的患者。根据粪便测试筛选结肠炎患者，然后根据结肠炎发病前的二甲双胍使用情况分为两组。我们收集了人口统计数据和结肠炎的临床信息，包括治疗和结果。结果共纳入953例患者。二甲双胍服用者的IMC发生率（7.6 %）高于非二甲双胍服用者(4.9 %；p & lt; 0.01)。结肠炎的特征和结局没有显著差异，除了二甲双胍使用者的住院时间更长(8天vs非二甲双胍使用者的6天； = 0.03页)。与未使用二甲双胍的IMC患者相比，二甲双胍的使用与更短的总生存期相关（p = 0.03）。我们的研究是第一个探讨二甲双胍对IMC和总生存率影响的研究。我们发现二甲双胍的使用可能与IMC的高风险相关。我们还发现二甲双胍的使用与IMC患者较短的总生存期之间存在关联。需要更大规模的风险分层分析研究来验证我们的发现。

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The association between metformin use, immune mediated colitis and overall survival in patients treated with checkpoint inhibitor

Introduction

Metformin is frequently prescribed to treat type 2 diabetes. Its primarily regulates hepatic and colonic glucose metabolism, but recent studies have suggested an anti-inflammatory effect, especially in colitis. It has been suggested that metformin may enhance immune checkpoint inhibition (ICI) efficacy for cancer treatment. Our study aims to explore the impact of metformin on ICI efficacy and the risk for colitis.

Methods

This was a single center, retrospective analysis of consecutive patients at a tertiary cancer center who received ICI between 01/2010–12/2022 and developed immune-mediated colitis (IMC). Patients were screened for colitis based on stool tests, then divided into two groups depending on metformin use prior to colitis onset. We collected data on demographic and colitis clinical information including treatments, and outcomes.

Results

A total of 953 patients were included. The incidence of IMC was higher among metformin users (7.6 %) than non-metformin users (4.9 %; p < 0.01). There were no significant differences in colitis features and outcomes, except for longer hospital stay among metformin users (8 days vs 6 for non-metformin users; p = 0.03). Metformin use was associated with shorter overall survival vs non-metformin users among patients with IMC (p = 0.03).

Discussion

Our study is among the first to explore the impact of metformin on IMC and overall survival. We found that metformin use may be associated with higher risk of IMC. We also found an association between metformin use and shorter overall survival among patients who developed IMC. Larger studies with risk-stratified analysis are needed to validate our findings.

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来源期刊

European Journal of Cancer 医学-肿瘤学

CiteScore

11.50

自引率

4.80%

发文量

953

审稿时长

23 days

期刊介绍： The European Journal of Cancer (EJC) serves as a comprehensive platform integrating preclinical, digital, translational, and clinical research across the spectrum of cancer. From epidemiology, carcinogenesis, and biology to groundbreaking innovations in cancer treatment and patient care, the journal covers a wide array of topics. We publish original research, reviews, previews, editorial comments, and correspondence, fostering dialogue and advancement in the fight against cancer. Join us in our mission to drive progress and improve outcomes in cancer research and patient care.