(1) Background: Recently, sodium–glucose cotransporter-2 inhibitors (SGLT2Is) have been reported to significantly reduce renal cell carcinoma (RCC) risk. However, the effect between individual SGLT2Is on RCC incidence in patients with type 2 diabetes (T2D) or heart failure is unclear. We conducted an observational analysis to explore type disparity in the prescription of SGLT2Is on RCC risk. (2) Methods: A nationwide retrospective cohort study using the Health and Welfare Data Science Center database (2016–2021) was conducted. Patients aged ≥40 years who took SGLT2Is were designated as the SGLT2I group, whereas propensity score 1:1-matched randomly selected patients without SGLT2Is were assigned to the non-SGLT2I group. The primary outcome was the risk of incident RCC between individual SGLT2Is. Multiple Cox regression modeling was conducted to analyze the association between individual SGLT2I use and RCC risk. (3) Results: After a 5.5-year follow-up, SGLT2I use was associated with a significantly lower risk of incident RCC (hazard: 0.62; 95% confidence interval [CI]: 0.44–0.89). Compared with non-users and after adjusting for the index year, sex, age, comorbidities, concurrent medication, and the risk of developing RCC, the hazard ratios of dapagliflozin, canagliflozin, and empagliflozin were 0.66 (95% CI: 0.53–0.83), 0.84 (95% CI: 0.46–1.30), and 0.71 (95% CI: 0.56–0.90), respectively. (4) Conclusions: Our data show a type-based effect of SGLT2Is on RCC risk. The type-based effect of SGLT2Is should be further studied for better clinical management information and for reducing RCC incidence in patients with T2D.
（1）背景：近期研究表明，钠-葡萄糖协同转运蛋白2抑制剂（SGLT2Is）可显著降低肾细胞癌（RCC）风险。然而，在2型糖尿病（T2D）或心力衰竭患者中，不同SGLT2I药物对RCC发病率的影响尚不明确。本研究通过观察性分析探讨不同SGLT2I药物处方对RCC风险的差异性影响。（2）方法：基于卫生福利数据科学中心数据库（2016-2021年）开展全国性回顾性队列研究。将年龄≥40岁且服用SGLT2Is的患者设为SGLT2I组，通过倾向评分1:1匹配随机选取未使用SGLT2Is的患者作为非SGLT2I组。主要结局指标为不同SGLT2I药物间的RCC发病风险。采用多变量Cox回归模型分析特定SGLT2I药物使用与RCC风险的相关性。（3）结果：经过5.5年随访，SGLT2Is使用与RCC发病风险显著降低相关（风险比：0.62；95%置信区间[CI]：0.44-0.89）。相较于未用药组，在调整索引年份、性别、年龄、合并症、联合用药及RCC发病风险后，达格列净、卡格列净和恩格列净的风险比分别为0.66（95% CI：0.53-0.83）、0.84（95% CI：0.46-1.30）和0.71（95% CI：0.56-0.90）。（4）结论：本研究数据显示SGLT2Is对RCC风险的影响存在药物类型差异。需进一步探究SGLT2Is的类型特异性效应，以优化临床管理策略并降低T2D患者的RCC发病率。
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