Departments of Epidemiology and Biostatistics (Iskander, Clemens, Dixon, Jeyakumar, Muanda, Garg), and Medicine (Clemens, Garg), Western University, London, Ont.; Department of Medicine, Division of Nephrology (Cherney), Toronto General Hospital, University of Toronto; Department of Physiology, and Banting and Best Diabetes Centre (Cherney), University of Toronto; Division of Nephrology (Harel, Wald), St. Michael's Hospital; Faculty of Medicine (Udell), University of Toronto; Cardiovascular Division (Udell), Department of Medicine and Women's College Research Institute, Women's College Hospital, Toronto, Ont.; Toronto, Ont.; ICES (Clemens, Dixon, Jeyakumar, McArthur, Muanda, Paterson, Garg), London, Ont.; Division of Nephrology (Parikh), School of Medicine, Johns Hopkins University, Baltimore, Md.; Department of Internal Medicine (Tangri), Max Rady College of Medicine, University of Manitoba; Seven Oaks General Hospital (Tangri), Chronic Disease Innovation Centre, Winnipeg, Man.
CMAJ. 2020 Apr 6;192(14):E351-E360. doi: 10.1503/cmaj.191283. Epub 2020 Apr 5.
Regulatory agencies warn about the risk of acute kidney injury (AKI) after the initiation of sodium-glucose cotransporter-2 (SGLT2) inhibitors. Our objective was to quantify the 90-day risk of AKI in older adults after initiation of SGLT2 inhibitors in routine clinical practice.
We conducted a population-based retrospective cohort study in Ontario, Canada, involving adults with diabetes who were aged 66 years or older and who were newly dispensed either an SGLT2 inhibitor or a dipeptidyl peptidase-4 (DPP4) inhibitor in an outpatient setting between 2015 and 2017. We used inverse probability of treatment weighting based on a propensity score to balance the 2 groups on measured baseline characteristics. The primary outcome was 90-day risk of a hospital encounter (i.e., visit to the emergency department or admission to hospital) with AKI, which we defined by a 50% or greater increase in the concentration of serum creatinine from the baseline value or an absolute increase of at least 27 μmol/L after an SGLT2 or DDP4 inhibitor was dispensed. We obtained weighted risk ratios using modified Poisson regression and weighted risk differences using binomial regression.
We included 39 094 patients with a median age of 70 (interquartile range 68-74) years in the study. Relative to new use of a DPP4 inhibitor, initiation of a SGLT2 inhibitor was associated with a lower 90-day risk of a hospital encounter with AKI: 216 events in 19 611 patients (1.10%) versus 388 events in 19 483 patients (1.99%); weighted risk ratio 0.79 (95% confidence interval 0.64-0.98).
In routine care of older adults, new use of SGLT2 inhibitors compared with use of DPP4 inhibitors was associated with a lower risk of AKI. Together with previous evidence, our findings suggest that regulatory warnings about AKI risk with SGLT2 inhibitors are unwarranted.
监管机构警告称，钠-葡萄糖共转运蛋白 2（SGLT2）抑制剂起始后会有急性肾损伤（AKI）的风险。我们的目的是在常规临床实践中，量化 SGLT2 抑制剂起始后老年患者 90 天 AKI 的风险。
我们在加拿大安大略省进行了一项基于人群的回顾性队列研究，纳入了在 2015 年至 2017 年期间，在门诊环境中新处方 SGLT2 抑制剂或二肽基肽酶-4（DPP4）抑制剂的年龄在 66 岁或以上的糖尿病患者。我们使用倾向评分逆概率治疗加权法，对两组患者的基线特征进行平衡。主要结局是 90 天内因 AKI 而发生的医院就诊（即急诊就诊或住院）的风险，AKI 通过血清肌酐浓度较基线值升高 50%或以上或在处方 SGLT2 或 DPP4 抑制剂后至少升高 27 μmol/L 来定义。我们使用校正泊松回归计算加权风险比，使用二项回归计算加权风险差。
本研究纳入了 39094 例患者，中位年龄为 70 岁（四分位距 68-74 岁）。与新使用 DPP4 抑制剂相比，起始 SGLT2 抑制剂与较低的 90 天 AKI 医院就诊风险相关：19611 例患者中有 216 例（1.10%），19483 例患者中有 388 例（1.99%）；加权风险比 0.79（95%置信区间 0.64-0.98）。
在老年患者的常规治疗中，与使用 DPP4 抑制剂相比，新使用 SGLT2 抑制剂与 AKI 风险降低相关。结合以往的证据，我们的研究结果表明，SGLT2 抑制剂 AKI 风险的监管警告是没有依据的。
