OBJECTIVE To assess the association between use of sodium-glucose co-transporter 2 (SGLT2) inhibitors and risk of serious renal events in data from routine clinical practice. DESIGN Cohort study using an active comparator, new user design and nationwide register data. SETTING Sweden, Denmark, and Norway, 2013-18. PARTICIPANTS Cohort of 29 887 new users of SGLT2 inhibitors (follow-up time: dapagliflozin 66.1%; empagliflozin 32.6%; canagliflozin 1.3%) and 29 887 new users of an active comparator, dipeptidyl peptidase-4 inhibitors, matched 1:1 on the basis of a propensity score with 57 variables. Mean follow-up time was 1.7 (SD 1.0) years. EXPOSURES SGLT2 inhibitors versus dipeptidyl peptidase-4 inhibitors, defined by filled prescriptions and analysed according to intention to treat. MAIN OUTCOME MEASURES The main outcome was serious renal events, a composite including renal replacement therapy, death from renal causes, and hospital admission for renal events. Secondary outcomes were the individual components of the main outcome. RESULTS The mean age of the study population was 61.3 (SD 10.5) years; 11 108 (19%) had cardiovascular disease, and 1974 (3%) had chronic kidney disease. Use of SGLT2 inhibitors, compared with dipeptidyl peptidase-4 inhibitors, was associated with a reduced risk of serious renal events (2.6 events per 1000 person years versus 6.2 events per 1000 person years; hazard ratio 0.42 (95% confidence interval 0.34 to 0.53); absolute difference -3.6 (-4.4 to -2.8) events per 1000 person years). In secondary outcome analyses, the hazard ratio for use of SGLT2 inhibitors versus dipeptidyl peptidase-4 inhibitors was 0.32 (0.22 to 0.47) for renal replacement therapy, 0.41 (0.32 to 0.52) for hospital admission for renal events, and 0.77 (0.26 to 2.23) for death from renal causes. In sensitivity analyses in each of the Swedish and Danish parts of the cohort, the model was further adjusted for glycated haemoglobin and estimated glomerular filtration rate (Sweden and Denmark) and for blood pressure, body mass index, and smoking (Sweden only); in these analyses, the hazard ratio moved from 0.41 (0.26 to 0.66) to 0.50 (0.31 to 0.81) in Sweden and from 0.42 (0.32 to 0.56) to 0.55 (0.41 to 0.74) in Denmark. CONCLUSIONS In this analysis using nationwide data from three countries, use of SGLT2 inhibitors, compared with dipeptidyl peptidase-4 inhibitors, was associated with a significantly reduced risk of serious renal events.

中文翻译：

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钠-葡萄糖共转运蛋白2抑制剂的使用和发生严重肾脏事件的风险：斯堪的纳维亚队列研究。

目的评估常规临床实践数据中钠-葡萄糖共转运蛋白2（SGLT2）抑制剂的使用与严重肾脏事件风险之间的关系。设计队列研究使用主动比较器，新用户设计和全国范围的注册数据。背景瑞典，丹麦和挪威，2013-18年。参与者共有29887名SGLT2抑制剂的新使用者（随访时间：达格列净66.1％；依帕列净32.6％；卡格列净1.3％）和29887名活性比较剂二肽基肽酶-4抑制剂的新使用者，在1：1上匹配具有57个变量的倾向得分的基础。平均随访时间为1.7（SD 1.0）年。暴露SGLT2抑制剂对二肽基肽酶-4抑制剂的定义已通过处方明确，并根据治疗意图进行了分析。主要观察指标主要结果是严重的肾脏事件，包括肾脏替代治疗，因肾脏原因死亡和因肾脏事件入院的综合症状。次要结果是主要结果的各个组成部分。结果研究人群的平均年龄为61.3（SD 10.5）岁。11 108（19％）人患有心血管疾病，1974年（3％）患者患有慢性肾脏疾病。与二肽基肽酶-4抑制剂相比，SGLT2抑制剂的使用与降低严重肾脏事件的风险相关（每1000人年2.6事件比每1000人年6.2事件；危险比0.42（95％置信区间0.34至0.53） ；每1000人年的绝对差异-3.6（-4.4至-2.8）事件）。在次要结果分析中，对于肾脏替代治疗，使用SGLT2抑制剂和二肽基肽酶-4抑制剂的风险比为0.32（0.22至0.47），对于因肾脏事件住院的患者，其风险比为0.41（0.32至0.52），对于因肾病死亡的患者为0.77（0.26至2.23）原因。在队列的瑞典和丹麦各部分的敏感性分析中，进一步针对糖化血红蛋白和估计的肾小球滤过率（瑞典和丹麦）以及血压，体重指数和吸烟（仅瑞典）对模型进行了调整；在这些分析中，危险比在瑞典从0.41（0.26至0.66）降至0.50（0.31至0.81），在丹麦从0.42（0.32至0.56）降至0.55（0.41至0.74）。结论在此分析中，我们使用了来自三个国家的全国性数据，将SGLT2抑制剂与二肽基肽酶4抑制剂的使用进行了比较，