GLP-1 receptor agonists and risk of hepatocellular carcinoma and all-cause mortality in patients with MASLD and type 2 diabetes: a propensity score–matched population-based cohort study

IF 7.4 3区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetes research and clinical practice Pub Date : 2025-08-11 DOI:10.1016/j.diabres.2025.112407

Wan-Ming Chen , Hui-Ji Ng , An-Tzu Jao , Szu-Yuan Wu , Ruey-Shyang Soong

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引用次数: 0

Abstract

Background

Hepatocellular carcinoma (HCC) is increasingly driven by non-viral causes, particularly metabolic dysfunction–associated steatotic liver disease (MASLD), which commonly coexists with type 2 diabetes mellitus (T2DM). Given the strong link between T2DM and HCC and the lack of approved pharmacologic preventive strategies, agents with dual metabolic and oncologic benefits are urgently needed. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have demonstrated anti-inflammatory, anti-fibrotic, and potential anti-tumor effects.

Methods

We conducted a multinational retrospective cohort study using the TriNetX global network to evaluate associations between GLP-1RA use and incident HCC in patients with MASLD and T2DM. Adults aged 18–90 years with both conditions were identified between 2005 and 2025. Primary outcome was incident HCC; secondary was all-cause mortality. Adjusted hazard ratios (aHRs) were estimated using Cox models.

Results

After matching, 152,329 patients were included in each group. GLP-1RA use was associated with lower risks of HCC (aHR, 0.64; 95% CI, 0.42–0.98) and all-cause mortality (aHR, 0.37; 95% CI, 0.36–0.38). Subgroup, sensitivity, and control analyses supported the robustness of findings.

Conclusions

GLP-1RA use was associated with significantly reduced risks of HCC and death in patients with MASLD and T2DM, supporting its potential for HCC chemoprevention.

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GLP-1受体激动剂与MASLD和2型糖尿病患者肝细胞癌和全因死亡率的风险：一项倾向评分匹配的基于人群的队列研究

背景：肝细胞癌（HCC）越来越多地由非病毒原因引起，特别是代谢功能障碍相关的脂肪变性肝病（MASLD），它通常与2型糖尿病（T2DM）共存。鉴于T2DM和HCC之间的紧密联系以及缺乏经批准的药物预防策略，迫切需要具有代谢和肿瘤双重益处的药物。胰高血糖素样肽-1受体激动剂（GLP-1RAs）已被证明具有抗炎、抗纤维化和潜在的抗肿瘤作用。方法：我们使用TriNetX全球网络进行了一项多国回顾性队列研究，以评估GLP-1RA的使用与MASLD和T2DM患者发生HCC之间的关系。在2005年至2025年期间，年龄在18-90岁之间的成年人被确定患有这两种疾病。主要结局是HCC的发生；其次是全因死亡率。校正风险比（aHRs）采用Cox模型估计。结果配对后，两组共纳入152329例患者。使用GLP-1RA与HCC风险降低相关(aHR, 0.64；95% CI, 0.42-0.98)和全因死亡率(aHR, 0.37；95% ci, 0.36-0.38)。亚组、敏感性和对照分析支持研究结果的稳健性。结论：glp - 1ra的使用与MASLD和T2DM患者HCC和死亡风险的显著降低相关，支持其对HCC化学预防的潜力。

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 research and clinical practice 医学-内分泌学与代谢

CiteScore

10.30

自引率

3.90%

发文量

862

审稿时长

32 days

期刊介绍： Diabetes Research and Clinical Practice is an international journal for health-care providers and clinically oriented researchers that publishes high-quality original research articles and expert reviews in diabetes and related areas. The role of the journal is to provide a venue for dissemination of knowledge and discussion of topics related to diabetes clinical research and patient care. Topics of focus include translational science, genetics, immunology, nutrition, psychosocial research, epidemiology, prevention, socio-economic research, complications, new treatments, technologies and therapy.