School of Pharmacy, University of Waterloo, Kitchener, Ontario, Canada.
Faculté de pharmacie, Université Laval, Laval, Quebec, Canada.
BMJ Open Diabetes Res Care. 2021 Dec;9(2). doi: 10.1136/bmjdrc-2021-002496.
To assess the comparative effectiveness and safety of renal-related outcomes associated with sodium-glucose cotransporter-2 inhibitors (SGLT2-i) initiation among patients with type 2 diabetes using real-world data.
We conducted a population-based cohort study using administrative healthcare data from Alberta (AB), Canada and primary care data from the Clinical Practice Research Datalink (CPRD), UK. From a cohort of new metformin users, we identified initiators of a SGLT2-i or dipeptidyl peptidase-4 inhibitor (DPP4-i) between January 1, 2014 and March 30, 2018 (AB) or between January 1, 2013 and November 29, 2018 (CPRD). Initiators of an SGLT2-i or DPP4-i were followed until death, disenrolment, therapy discontinuation, or study end date. The effectiveness outcome was renal disease progression, defined as a composite of new-onset macroalbuminuria, serum creatinine doubling with estimated glomerular filtration rate of ≤45 mL/min/1.73 m, renal replacement therapy, hospital admission or death from renal causes. The safety outcome was hospitalization due to acute kidney injury (AKI). We adjusted for confounding using high-dimensional propensity score matching and estimated HRs using Cox proportional hazards regression. Aggregate data from each database were combined by random-effects meta-analysis.
Among the 29 465 included patients (20 564 AB, 8901 CPRD), 37.5% were new SGLT2-i users in AB and 21.3% in CPRD. Compared with DPP4 initiators, SGLT2-i initiators were associated with a reduced risk of renal disease progression (pooled HR 0.79, 95% CI 0.62 to 1.00); however, there was no significant difference in the risk of AKI (pooled HR 0.89, 95% CI 0.58 to 1.36). These findings were consistent with other exposure definitions and antidiabetic comparators.
Our findings support a renoprotective effect of SGLT2-i without an increased risk of AKI, compared with clinically relevant active comparators.
使用来自加拿大阿尔伯塔省（AB）的医疗保健管理数据和英国临床实践研究数据链（CPRD）的初级保健数据，评估 2 型糖尿病患者中使用钠-葡萄糖共转运蛋白-2 抑制剂（SGLT2-i）与肾相关结局的比较有效性和安全性。
我们进行了一项基于人群的队列研究，纳入了新开始使用二甲双胍的患者队列，在 2014 年 1 月 1 日至 2018 年 3 月 30 日（AB）或 2013 年 1 月 1 日至 2018 年 11 月 29 日（CPRD）期间，识别出 SGLT2-i 或二肽基肽酶-4 抑制剂（DPP4-i）的起始使用者。SGLT2-i 或 DPP4-i 的起始使用者随访至死亡、退出、停药或研究结束日期。有效性结局为肾脏疾病进展，定义为新发大量白蛋白尿、估算肾小球滤过率≤45 mL/min/1.73 m 时血清肌酐倍增、肾脏替代治疗、住院或肾脏原因导致的死亡的复合结局。安全性结局为急性肾损伤（AKI）住院。我们通过高维倾向评分匹配调整混杂因素，并使用 Cox 比例风险回归估计 HR。通过随机效应荟萃分析对每个数据库的汇总数据进行合并。
在纳入的 29465 例患者（AB 20564 例，CPRD 8901 例）中，37.5%为 AB 新 SGLT2-i 使用者，21.3%为 CPRD 新 SGLT2-i 使用者。与 DPP4 起始使用者相比，SGLT2-i 起始使用者的肾脏疾病进展风险降低（汇总 HR 0.79，95%CI 0.62 至 1.00）；然而，AKI 风险无显著差异（汇总 HR 0.89，95%CI 0.58 至 1.36）。这些发现与其他暴露定义和抗糖尿病对照物一致。
与临床相关的活性对照物相比，我们的研究结果支持 SGLT2-i 具有肾脏保护作用，且不会增加 AKI 风险。
