Abstract：
OBJECTIVE: Sodium-glucose cotransporter 2 inhibitors (SGLT-2is) have been demonstrated to be associated with cancer cell mechanisms. However, whether they increase the risk of cancer remains unclear. Thus, this study aimed to determine the association between SGLT-2i use and the incidence of cancer in patients with diabetes mellitus (DM) in Taiwan.
METHODS: This retrospective cohort study was based on the Taiwan National Health Insurance database. The study population comprised patients with DM, and those who first used SGLT-2is during 2016-2018 were assigned to the study group. Greedy propensity score matching was performed to select patients who first used dipeptidyl peptidase 4 inhibitors (DPP-4is), and these patients were assigned to the control group. A Cox proportional hazards model was used to estimate the adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for cancer risk in the study and control groups; this model was adjusted for demographic characteristics, DM severity, comorbidities and concomitant medication use.
RESULTS: After controlling for relevant variables, the SGLT-2i cohort (aHR = 0.90, 95% CI = 0.87-0.93) had a significantly lower risk of developing cancer than the DPP-4i cohort, particularly when the SGLT-2i was dapagliflozin (aHR = 0.91, 95% CI = 0.87-0.95) or empagliflozin (aHR = 0.90, 95% CI = 0.86-0.94). Regarding cancer type, the SGLT-2i cohort\'s risk of cancer was significantly lower than that of the DPP-4i cohort for leukaemia, oesophageal, colorectal, liver, pancreatic, lung, skin and bladder cancer.
CONCLUSIONS: SGLT-2i use was associated with a significantly lower risk of cancer than DPP-4i use.
METHODS: This retrospective cohort study was based on the Taiwan National Health Insurance database. The study population comprised patients with DM, and those who first used SGLT-2is during 2016-2018 were assigned to the study group. Greedy propensity score matching was performed to select patients who first used dipeptidyl peptidase 4 inhibitors (DPP-4is), and these patients were assigned to the control group. A Cox proportional hazards model was used to estimate the adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for cancer risk in the study and control groups; this model was adjusted for demographic characteristics, DM severity, comorbidities and concomitant medication use.
RESULTS: After controlling for relevant variables, the SGLT-2i cohort (aHR = 0.90, 95% CI = 0.87-0.93) had a significantly lower risk of developing cancer than the DPP-4i cohort, particularly when the SGLT-2i was dapagliflozin (aHR = 0.91, 95% CI = 0.87-0.95) or empagliflozin (aHR = 0.90, 95% CI = 0.86-0.94). Regarding cancer type, the SGLT-2i cohort\'s risk of cancer was significantly lower than that of the DPP-4i cohort for leukaemia, oesophageal, colorectal, liver, pancreatic, lung, skin and bladder cancer.
CONCLUSIONS: SGLT-2i use was associated with a significantly lower risk of cancer than DPP-4i use.
摘要：
目的：钠-葡萄糖协同转运蛋白2抑制剂（SGLT-2is）已被证明与癌细胞机制有关。然而,它们是否会增加患癌症的风险尚不清楚。因此，本研究旨在确定台湾糖尿病(DM)患者使用SGLT-2i与癌症发病率之间的关系.
方法：本回顾性队列研究基于台湾国民健康保险数据库。研究人群包括DM患者，在2016-2018年首次使用SGLT-2is的患者被分配到研究组.进行贪婪倾向评分匹配以选择首次使用二肽基肽酶4抑制剂（DPP-4is）的患者，这些患者被分配到对照组。Cox比例风险模型用于估计研究组和对照组癌症风险的调整风险比（aHRs）和95％置信区间（CIs）；该模型针对人口统计特征进行了调整，DM严重程度,合并症和合并用药。
结果：控制相关变量后，SGLT-2i队列(aHR=0.90,95%CI=0.87-0.93)患癌症的风险显著低于DPP-4i队列,特别是当SGLT-2i为达格列净(aHR=0.91,95%CI=0.87-0.95)或依格列净(aHR=0.90,95%CI=0.86-0.94)时.关于癌症类型，SGLT-2i队列的癌症风险显著低于DPP-4i队列的白血病风险，食道,结直肠,肝脏,胰腺,肺，皮肤癌和膀胱癌.
结论：与使用DPP-4i相比，使用SGLT-2i与癌症风险显著降低相关。
方法：本回顾性队列研究基于台湾国民健康保险数据库。研究人群包括DM患者，在2016-2018年首次使用SGLT-2is的患者被分配到研究组.进行贪婪倾向评分匹配以选择首次使用二肽基肽酶4抑制剂（DPP-4is）的患者，这些患者被分配到对照组。Cox比例风险模型用于估计研究组和对照组癌症风险的调整风险比（aHRs）和95％置信区间（CIs）；该模型针对人口统计特征进行了调整，DM严重程度,合并症和合并用药。
结果：控制相关变量后，SGLT-2i队列(aHR=0.90,95%CI=0.87-0.93)患癌症的风险显著低于DPP-4i队列,特别是当SGLT-2i为达格列净(aHR=0.91,95%CI=0.87-0.95)或依格列净(aHR=0.90,95%CI=0.86-0.94)时.关于癌症类型，SGLT-2i队列的癌症风险显著低于DPP-4i队列的白血病风险，食道,结直肠,肝脏,胰腺,肺，皮肤癌和膀胱癌.
结论：与使用DPP-4i相比，使用SGLT-2i与癌症风险显著降低相关。
