Department of Environmental and Occupational Health, School of Public Health, Indiana University, Bloomington, Indiana, United States of America.
Indiana University Simon Cancer Center, Indianapolis, Indiana, United States of America.
PLoS One. 2022 Sep 12;17(9):e0274519. doi: 10.1371/journal.pone.0274519. eCollection 2022.
Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a relatively new class of antidiabetic drugs. Emerging findings from laboratory studies indicate that SGLT2 inhibitors can improve liver function and suppress the proliferation of hepatocellular carcinoma (HCC) cells. The aim of this study was to test the hypothesis that initiation of SGLT2 inhibitors improves HCC prognosis in a human population.
We used National Surveillance, Epidemiology and End Results (SEER)-Medicare linked data in the United States to evaluate the role of SGLT2 inhibitor initiation on the survival of HCC patients. 3,185 HCC patients newly diagnosed between 2014 and 2017 aged 66 years or older with pre-existing type 2 diabetes were included and followed to the end of 2019. Information on SGLT2 inhibitor initiation was extracted from the Medicare Part D file.
SGLT2 inhibitor initiation was associated with significantly lower mortality risk after adjusting for potential confounders (HR = 0.68, 95% CI = 0.54-0.86) with stronger association for longer duration of use (HR = 0.60, 95% CI = 0.41-0.88). Further, we found that SGLT2 inhibitor initiation was associated with a lower risk mortality risk ranging from 14% to 60% regardless of patient demographic variables, tumor characteristics, and cancer treatments.
Our large SEER-Medicare linked data study indicates that SGLT2 inhibitor initiation was associated with improved overall survival of HCC patients with pre-existing type 2 diabetes compared with no SGLT2 inhibitor use. Further studies are needed to confirm our findings and elucidate the possible mechanisms behind the association.
钠-葡萄糖共转运蛋白 2（SGLT2）抑制剂是一类新型的抗糖尿病药物。实验室研究的新发现表明，SGLT2 抑制剂可以改善肝功能并抑制肝细胞癌（HCC）细胞的增殖。本研究旨在检验这样一个假设，即 SGLT2 抑制剂的启动可以改善人群中 HCC 的预后。
我们使用美国国家监测、流行病学和结果（SEER）-医疗保险链接数据来评估 SGLT2 抑制剂启动对 HCC 患者生存的作用。纳入了 2014 年至 2017 年间新诊断为年龄在 66 岁或以上且患有 2 型糖尿病的 HCC 患者 3185 例，并随访至 2019 年底。SGLT2 抑制剂启动的信息从医疗保险部分 D 文件中提取。
在调整了潜在混杂因素后，SGLT2 抑制剂的启动与死亡率风险显著降低相关（HR=0.68，95%CI=0.54-0.86），且与使用时间较长的关联更强（HR=0.60，95%CI=0.41-0.88）。此外，我们发现，无论患者的人口统计学变量、肿瘤特征和癌症治疗如何，SGLT2 抑制剂的启动与死亡率风险降低 14%至 60%相关。
我们的大型 SEER-医疗保险链接数据研究表明，与不使用 SGLT2 抑制剂相比，SGLT2 抑制剂的启动与患有 2 型糖尿病的 HCC 患者的总体生存率提高相关。需要进一步的研究来证实我们的发现并阐明关联背后的可能机制。
