OBJECTIVE Sodium-glucose cotransporter-2 (SGLT2) inhibitors are new medications that improve cardiovascular and renal outcomes in patients with type 2 diabetes (T2D). However, the Food and Drug Administration has issued alerts regarding increased acute kidney injury (AKI) risk with canagliflozin and dapagliflozin. We aimed to assess the real-world risk of AKI in new SGLT2 inhibitor users in two large health care utilization cohorts of patients with T2D.

RESEARCH DESIGN AND METHODS We used longitudinal data from the Mount Sinai chronic kidney disease registry and the Geisinger Health System cohort. We selected SGLT inhibitor users and nonusers (patients with T2D without SGLT2 inhibitor prescription). We determined AKI by the KDIGO (Kidney Disease: Improving Global Outcomes) definition (AKI_KDIGO). We performed 1:1 nearest-neighbor propensity matching and calculated unadjusted hazard ratios (HRs) and adjusted HRs (aHRs; accounting for covariates poorly balanced) for AKI in primary and sensitivity analyses.

RESULTS We identified 377 SGLT2 inhibitor users and 377 nonusers in the Mount Sinai cohort, of whom 3.8 and 9.7%, respectively, had an AKI_KDIGO event over a median follow-up time of 14 months. The unadjusted hazards of AKI_KDIGO were 60% lower in users (HR 0.4 [95% CI 0.2–0.7]; P = 0.01), which was unchanged (aHR 0.4 [95% CI 0.2–0.7]; P = 0.004) postadjustment. Similarly, we identified 1,207 SGLT2 inhibitor users and 1,207 nonusers in the Geisinger cohort, of whom 2.2 and 4.6% had an AKI_KDIGO event. AKI_KDIGO unadjusted hazards were lower in users (HR 0.5 [95% CI 0.3–0.8]; P < 0.01) with modest attenuation postadjustment for covariates (aHR 0.6 [95% CI 0.4–1.1]; P = 0.09). These estimates did not qualitatively change across several sensitivity analyses.

CONCLUSIONS Our findings do not suggest an increased risk of AKI associated with SGLT2 inhibitor use in patients with T2D in two large health systems.

目的葡萄糖钠转运蛋白2（SGLT2）抑制剂是改善2型糖尿病（T2D）患者心血管和肾脏结局的新药。但是，美国食品药品监督管理局（FDA）已发布有关canagliflozin和dapagliflozin导致急性肾损伤（AKI）风险增加的警告。我们旨在评估在两个大型的T2D患者医疗保健利用队列中，新的SGLT2抑制剂使用者中AKI的现实风险。

研究设计和方法我们使用了西奈山慢性肾脏病登记处和Geisinger卫生系统研究组的纵向数据。我们选择了SGLT抑制剂的使用者和非使用者（患有T2D且未使用SGLT2抑制剂处方的患者）。我们通过KDIGO（肾脏疾病：改善全球结局）定义（AKI _KDIGO）确定了AKI 。在主要和敏感性分析中，我们对AKI进行了1：1最近邻倾向匹配，并计算了AKI的未调整风险比（HR）和调整后的HR（aHR；考虑协变量平衡性差）。

结果我们在西奈山队列中确定了377名SGLT2抑制剂使用者和377名非使用者，其中中位随访时间为14个月，分别有3.8％和9.7％发生了AKI _KDIGO事件。使用AKI _KDIGO的未经调整的危险在使用者中降低了60％（HR 0.4 [95％CI 0.2-0.7]；P = 0.01），而在调整后未发生变化（aHR 0.4 [95％CI 0.2-0.7]；P = 0.004）。同样，我们在Geisinger队列中确定了1,207名SGLT2抑制剂使用者和1,207名非使用者，其中2.2％和4.6％发生了AKI _KDIGO事件。用户的AKI _KDIGO未经调整的危险性较低（HR 0.5 [95％CI 0.3-0.8]；P<0.01），并对协变量进行了适度的衰减后调整（aHR 0.6 [95％CI 0.4–1.1]；P = 0.09）。这些估计在几个敏感性分析中没有定性变化。

结论我们的发现并不表明在两个大型卫生系统中的T2D患者中使用SGLT2抑制剂会增加AKI的风险。