Abstract：
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
摘要：
背景：2型糖尿病（T2DM）可能是肝细胞癌（HCC）发展的危险因素。发展为HCC的风险与钠-葡萄糖协同转运蛋白-2抑制剂（SGLT2i）与二肽基肽酶-4抑制剂（DPP4i）治疗之间的关联目前尚不清楚。本研究旨在比较SGLT2i与DPP4i治疗患者新发HCC的风险。
方法：这是一项2015年1月1日至2020年12月31日在香港接受SGLT2i或DPP4i治疗的T2DM患者的回顾性队列研究。同时使用DPP4i和SGLT2i的患者被排除。通过使用最近邻搜索进行倾向得分匹配(1:1比率)。应用多变量Cox回归来识别显著的预测因子。
结果：共纳入62,699例患者（SGLT2i，n=22,154；DPP4i，n=40,545)。匹配后（n=44,308），166名患者（0.37％）发展为HCC：SGLT2i组36名，DPP4i组130名，超过240,269人年。总的来说,SGLT2i的使用与HCC的风险较低相关(风险比[HR]，0.42；95%CI，0.28-0.79）与调整后的DPP4i相比。在肝硬化或晚期纤维化患者中，SGLT2i与HCC发展之间的关联仍然显着（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）。结果在不同的风险模型中是一致的，倾向得分方法，和敏感性分析。
结论：在调整后，与使用DPP4i相比，使用SGLT2i与较低的HCC风险相关，在肝硬化的背景下，晚期纤维化，HBV感染，和HCV感染。
方法：这是一项2015年1月1日至2020年12月31日在香港接受SGLT2i或DPP4i治疗的T2DM患者的回顾性队列研究。同时使用DPP4i和SGLT2i的患者被排除。通过使用最近邻搜索进行倾向得分匹配(1:1比率)。应用多变量Cox回归来识别显著的预测因子。
结果：共纳入62,699例患者（SGLT2i，n=22,154；DPP4i，n=40,545)。匹配后（n=44,308），166名患者（0.37％）发展为HCC：SGLT2i组36名，DPP4i组130名，超过240,269人年。总的来说,SGLT2i的使用与HCC的风险较低相关(风险比[HR]，0.42；95%CI，0.28-0.79）与调整后的DPP4i相比。在肝硬化或晚期纤维化患者中，SGLT2i与HCC发展之间的关联仍然显着（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）。结果在不同的风险模型中是一致的，倾向得分方法，和敏感性分析。
结论：在调整后，与使用DPP4i相比，使用SGLT2i与较低的HCC风险相关，在肝硬化的背景下，晚期纤维化，HBV感染，和HCV感染。
