{"title":"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","authors":"Wan-Ming Chen , Hui-Ji Ng , An-Tzu Jao , Szu-Yuan Wu , Ruey-Shyang Soong","doi":"10.1016/j.diabres.2025.112407","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusions</h3><div>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.</div></div>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":"227 ","pages":"Article 112407"},"PeriodicalIF":7.4000,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"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\",\"authors\":\"Wan-Ming Chen , Hui-Ji Ng , An-Tzu Jao , Szu-Yuan Wu , Ruey-Shyang Soong\",\"doi\":\"10.1016/j.diabres.2025.112407\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusions</h3><div>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.</div></div>\",\"PeriodicalId\":11249,\"journal\":{\"name\":\"Diabetes research and clinical practice\",\"volume\":\"227 \",\"pages\":\"Article 112407\"},\"PeriodicalIF\":7.4000,\"publicationDate\":\"2025-08-11\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Diabetes research and clinical practice\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0168822725004218\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Diabetes research and clinical practice","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0168822725004218","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
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
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.
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.