{
  "abstract": "Background Recurrence after curative-intent resection remains common in hepatocellular carcinoma (HCC), and whether postoperative incretin-based treatment choice influences outcomes in patients with type 2 diabetes (T2D) is unclear.Objective To determine whether postoperative initiation of glucagon-like peptide-1 receptor agonists (GLP-1RAs), compared with dipeptidyl peptidase-4 inhibitors (DPP-4is), is associated with improved recurrence-free and overall survival after curative-intent resection for HCC.Design Active-comparator, new-user target trial emulation using electronic medical records from 36 hospitals across China from 2014 to 2023, with follow-up through 1 October 2025. Eligible adults had histologically confirmed HCC and T2D, underwent R0 resection and initiated a GLP-1RA or DPP-4i within postoperative days 0 to 90. Time zero was the first qualifying prescription or order date. The primary estimand was intention-to-treat; a prespecified per-protocol analysis assessed sustained adherence. The primary outcome was recurrence-free survival (RFS), treating death without recurrence as a competing event; overall survival (OS) was secondary. The study was registered with the Chinese Clinical Trial Registry (ChiCTR2600118495).Results Among 42 855 patients with HCC and T2D who underwent liver resection, 1249 were included in the final analytical cohort, including 723 DPP-4i initiators and 526 GLP-1RA initiators; median follow-up was 50.8 months. In weighted intention-to-treat analyses, GLP-1RA versus DPP-4i initiation was associated with longer RFS (cause-specific HR 0.80, 95% CI 0.67 to 0.96; p=0.016) and OS (HR 0.58, 95% CI 0.47 to 0.71; p<0.001). Per-protocol analyses were directionally consistent.Conclusion Postoperative GLP-1RA initiation, compared with DPP-4i initiation, was associated with delayed recurrence and longer OS; prospective confirmation is warranted.Trial registration number ChiCTR2600118495.",
  "authors": [
    {
      "affiliations": [
        "Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China",
        "Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China"
      ],
      "name": "Yan-Jun Xiang"
    },
    {
      "affiliations": [
        "Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China"
      ],
      "name": "Zong-Han Liu"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary Surgery, No. 971 Hospital of the People’s Liberation Army Navy, Qingdao, Shandong, China"
      ],
      "name": "Jin-Kai Feng"
    },
    {
      "affiliations": [
        "Department of Health Statistics, Naval Medical University, Shanghai, China"
      ],
      "name": "Ying-Yi Qin"
    },
    {
      "affiliations": [
        "Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China"
      ],
      "name": "Hong-Ming Yu"
    },
    {
      "affiliations": [
        "Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China"
      ],
      "name": "Yu-Qiang Cheng"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China"
      ],
      "name": "Gang Chen"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary and Pancreatic Surgery, Fujian Provincial Hospital, Fuzhou, Fujian, China"
      ],
      "name": "Jia-Yi Wu"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary and Pancreatic Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian, China"
      ],
      "name": "Yong-Yi Zeng"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary Surgery, General Hospital of Northern Theater Command, Shenyang, Liaoning, China"
      ],
      "name": "Yu-Fu Tang"
    },
    {
      "affiliations": [
        "Hepatobiliary Center, the First Affiliated Hospital of Nanjing Medical University, Research Unit of Liver Transplantation and Transplant Immunology, Chinese Academy of Medical Sciences, Nanjing, Jiangsu, China"
      ],
      "name": "Jian-Hua Rao"
    },
    {
      "affiliations": [
        "Department of General Surgery, Shanghai Tenth People’s Hospital, Shanghai, China"
      ],
      "name": "Feng-Min Zhang"
    },
    {
      "affiliations": [
        "Department of Comprehensive Surgery, Nantong First People’s Hospital, Nantong, Jiangsu, China"
      ],
      "name": "Shi-Ye Yang"
    },
    {
      "affiliations": [
        "Department of Pathology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China"
      ],
      "name": "Gui-Ran Wang"
    },
    {
      "affiliations": [
        "Department of Hepatic Surgery, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China"
      ],
      "name": "Lin-Sen Ye"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary and Pancreaticosplenic Surgery, Beijing Chaoyang Hospital, Beijing, China"
      ],
      "name": "Ren Lang"
    },
    {
      "affiliations": [
        "Department of General Surgery, the Second Affiliated Hospitals of Wenzhou Medical University, Wenzhou, Zhejiang, China"
      ],
      "name": "Jian-Hua Lin"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary and Pancreatic Surgery, Ningbo No.2 Hospital, Ningbo, Zhejiang, China"
      ],
      "name": "Yi-Tao Zheng"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary and Pancreatic Surgery, Ningbo Medical Treatment Center Lihuili Hospital, Ningbo University, Ningbo, Zhejiang, China"
      ],
      "name": "Ye-Fan Mao"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary and Pancreatic Surgery, the First Hospital of Jiaxing, Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, China"
      ],
      "name": "Hong-Kun Zhou"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary and Pancreatic Surgery, Fujian Provincial Hospital, Fuzhou, Fujian, China"
      ],
      "name": "Mao-Lin Yan"
    },
    {
      "affiliations": [
        "Department of Oncology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China"
      ],
      "name": "Chao Liang"
    },
    {
      "affiliations": [
        "Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China",
        "Department of Oncology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China"
      ],
      "name": "Si-Si Ren"
    },
    {
      "affiliations": [
        "Department of Hepatic Surgery, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China"
      ],
      "name": "Kang Wang"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary Surgery, No. 971 Hospital of the People’s Liberation Army Navy, Qingdao, Shandong, China"
      ],
      "name": "Lin Gong"
    },
    {
      "affiliations": [
        "Department of Liver Transplantation and Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China"
      ],
      "name": "Shuai Xu"
    },
    {
      "affiliations": [
        "Department of General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China"
      ],
      "name": "Yun-Fei Xu"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China"
      ],
      "name": "Qing-Qiang Ni"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary Surgery, the Second Hospital Affiliated to NanChang University, Nanchang, Jiangxi, China"
      ],
      "name": "Kai Wang"
    },
    {
      "affiliations": [
        "Department of General Surgery, the 940Th Hospital of Joint Logistics Support Force of Chinese People's Liberation Army, Lanzhou, Gansu, China"
      ],
      "name": "Rui-Fang Fan"
    },
    {
      "affiliations": [
        "Department of General Surgery, General Hospital of Central Theater Command, Wuhan, Hubei, China"
      ],
      "name": "Yi-Lin Hu"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary and Pancreatic Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China"
      ],
      "name": "Tao Jiang"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary and Pancreatic Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China"
      ],
      "name": "Chao Lin"
    },
    {
      "affiliations": [
        "Department of General Surgery, Shandong Provincial Third Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China"
      ],
      "name": "Qing-Lun Gao"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary Surgery, the Fifth People's Hospital of Datong, Datong, Shanxi, China"
      ],
      "name": "Zhi-Qiang Wang"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary Surgery, Xing'an League People's Hospital, Hinggan, Inner Mongolia, China"
      ],
      "name": "Yi-Meng Lu"
    },
    {
      "affiliations": [
        "Department of General Surgery, No. 924 Hospital of Chinese People's Liberation Army Joint Logistic Support Force, Guilin, Guangxi, China"
      ],
      "name": "Wen-Bo Zou"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary Surgery, Chinese People's Liberation Army 970th Hospital, Taiyuan, Shanxi, China"
      ],
      "name": "Xiao Wang"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary Surgery, Chinese People's Liberation Army 920th Hospital, Kunming, Yunnan, China"
      ],
      "name": "Chen Feng"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary Surgery, Hunan Provincial People's Hospital, First Affiliated Hospital of Hunan Normal University, Changsha, Hunan, China"
      ],
      "name": "Zi-Cheng Wang"
    },
    {
      "affiliations": [
        "Department of General Surgery, the 989th Hospital of the Joint Logistics Support Force of Chinese People's Liberation Army, Luoyang, Henan, China"
      ],
      "name": "Peng-Jiong Liu"
    },
    {
      "affiliations": [
        "Department of General Surgery, Taiyuan People's Hospital, Taiyuan, Shanxi, China"
      ],
      "name": "Wen-Jing Wei"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary Surgery, Affiliated Hospital of Binzhou Medical University, Binzhou, Shandong, China"
      ],
      "name": "Fan Zhang"
    },
    {
      "affiliations": [
        "Department of Hepatology, the Sixth People's Hospital of Shenyang, Shenyang, Liaoning, China"
      ],
      "name": "Wei Wu"
    },
    {
      "affiliations": [
        "Department of General Surgery, Shaoxing University Affiliated Hospital, Shaoxing, Zhejiang, China"
      ],
      "name": "Hao-Feng Lu"
    },
    {
      "affiliations": [
        "CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China"
      ],
      "name": "Jing-Yi Huang"
    },
    {
      "affiliations": [
        "CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China"
      ],
      "name": "Xin Liang"
    },
    {
      "affiliations": [
        "CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China"
      ],
      "name": "Jing-Jing Li"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China"
      ],
      "name": "Yun-Feng Shan"
    },
    {
      "affiliations": [
        "Senior Department of Hepato-Pancreato-Biliary Surgery, the First Medical Center of Chinese People's Liberation Army General Hospital, Institute of Hepatobiliary Surgery of Chinese PLA, Chinese PLA Medical School, Beijing, China"
      ],
      "name": "Xiu-Ping Zhang"
    },
    {
      "affiliations": [
        "Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China",
        "Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China"
      ],
      "name": "Shu-Qun Cheng"
    },
    {
      "affiliations": [],
      "name": "Chinese Association of Liver Cancer and Chinese Medical Doctor Association"
    }
  ],
  "title": "Glucagon-like peptide-1 receptor agonists versus dipeptidyl peptidase-4 inhibitors after liver resection for hepatocellular carcinoma in patients with type 2 diabetes: a target trial emulation study",
  "uid": "d9921630-1465-520e-969a-e69f150508ef"
}