1Division of Clinical Pharmacology and Therapeutics, Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China.
2Diabetes Research Unit, Cardiovascular Analytics Group, PowerHealth Research Institute, Hong Kong, China.
J Natl Compr Canc Netw. 2024 Jun;22(2 D). doi: 10.6004/jnccn.2023.7118.
Type 2 diabetes mellitus (T2DM) may be a risk factor for development of hepatocellular carcinoma (HCC). The association between risk of developing HCC and treatment with sodium-glucose cotransporter-2 inhibitors (SGLT2i) versus dipeptidyl peptidase-4 inhibitors (DPP4i) is currently unknown. This study aimed to compare the risk of new-onset HCC in patients treated with SGLT2i versus DPP4i.
This was a retrospective cohort study of patients with T2DM in Hong Kong receiving either SGLT2i or DPP4i between January 1, 2015, and December 31, 2020. Patients with concurrent DPP4i and SGLT2i use were excluded. Propensity score matching (1:1 ratio) was performed by using the nearest neighbor search. Multivariable Cox regression was applied to identify significant predictors.
A total of 62,699 patients were included (SGLT2i, n=22,154; DPP4i, n=40,545). After matching (n=44,308), 166 patients (0.37%) developed HCC: 36 in the SGLT2i group and 130 in the DPP4i group over 240,269 person-years. Overall, SGLT2i use was associated with lower risks of HCC (hazard ratio [HR], 0.42; 95% CI, 0.28-0.79) compared with DPP4i after adjustments. The association between SGLT2i and HCC development remained significant in patients with cirrhosis or advanced fibrosis (HR, 0.12; 95% CI, 0.04-0.41), hepatitis B virus (HBV) infection (HR, 0.32; 95% CI, 0.17-0.59), or hepatitis C virus (HCV) infection (HR, 0.41; 95% CI, 0.22-0.80). The results were consistent in different risk models, propensity score approaches, and sensitivity analyses.
SGLT2i use was associated with a lower risk of HCC compared with DPP4i use after adjustments, and in the context of cirrhosis, advanced fibrosis, HBV infection, and HCV infection.
2 型糖尿病（T2DM）可能是肝细胞癌（HCC）发展的一个风险因素。目前尚不清楚使用钠-葡萄糖共转运蛋白 2 抑制剂（SGLT2i）与二肽基肽酶-4 抑制剂（DPP4i）治疗与 HCC 发病风险之间的关系。本研究旨在比较 SGLT2i 与 DPP4i 治疗的患者新发 HCC 的风险。
这是一项回顾性队列研究，纳入了 2015 年 1 月 1 日至 2020 年 12 月 31 日期间在香港接受 SGLT2i 或 DPP4i 治疗的 T2DM 患者。排除同时使用 DPP4i 和 SGLT2i 的患者。采用最近邻搜索法进行倾向评分匹配（1:1 比例）。采用多变量 Cox 回归识别显著预测因素。
共纳入 62699 例患者（SGLT2i 组 22154 例，DPP4i 组 40545 例）。匹配后（n=44308），166 例患者（0.37%）发生 HCC：SGLT2i 组 36 例，DPP4i 组 130 例，随访 240269 人年。总体而言，与 DPP4i 相比，SGLT2i 治疗 HCC 风险较低（风险比[HR]，0.42；95%CI，0.28-0.79），经调整后差异仍有统计学意义。在肝硬化或晚期纤维化（HR，0.12；95%CI，0.04-0.41）、乙型肝炎病毒（HBV）感染（HR，0.32；95%CI，0.17-0.59）或丙型肝炎病毒（HCV）感染（HR，0.41；95%CI，0.22-0.80）患者中，SGLT2i 与 HCC 发生的相关性仍有统计学意义。在不同风险模型、倾向评分方法和敏感性分析中，结果均一致。
经调整后，与 DPP4i 相比，SGLT2i 治疗 HCC 的风险较低，且在肝硬化、晚期纤维化、HBV 感染和 HCV 感染情况下也是如此。
