Department of Medicine, Division of Nephrology and Hypertension (Hung), Vanderbilt University Medical Center; Precision Nephrology Program (Hung), Vanderbilt University Medical Center; Geriatric Research Education Clinical Center (Hung, Hackstadt, Grijalva, Greevy Jr., Roumie), Veteran Administration Tennessee Valley Healthcare System; Department of Medicine (Roumie), Vanderbilt University Medical Center; Department of Biostatistics (Hackstadt, Greevy Jr.), Vanderbilt University School of Medicine; Department of Health Policy (Griffin, Grijalva, Roumie), Vanderbilt University Medical Center, Nashville, Tenn.
CMAJ Open. 2023 Jan 31;11(1):E77-E89. doi: 10.9778/cmajo.20210207. Print 2023 Jan-Feb.
Diabetes often causes kidney disease. In this study, we sought to evaluate if metformin use was associated with death or kidney events in patients with diabetes and concurrent reduced kidney function.
We used data from the Veterans Health Administration, Medicare and National Death Index databases to assemble a national retrospective cohort of veterans who were using metformin or sulfonylureas from 2001 through 2016 and who began follow-up at an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73 m. The primary composite outcome was a kidney event (i.e., 40% decline in eGFR or end-stage renal disease) or death. The secondary outcome was a kidney event (eGFR decline or end-stage renal disease). We weighted the cohort using propensity scores and used Cox proportional models to estimate the cause-specific hazard of outcomes and of treatment nonpersistence as a competing risk. We stratified follow-up into 2 periods, namely the first 360 days from the start of follow-up, and 361 days and beyond.
In the first 360 days, the propensity score-weighted cohort included 24 883 patients who used metformin and 24 998 who used sulfonylureas. There were 33.5 (95% confidence interval [CI] 30.9-36.3) and 43.0 (95% CI 40.1-46.0) deaths or kidney events per 1000 person-years for patients who used metformin or sulfonylureas, respectively (hazard ratio [HR] 0.78, 95% CI 0.71-0.85). For the secondary outcome of kidney events, the HR was 0.94 (95% CI 0.67-1.33). In the second period from 361 days onward, the primary outcome event rate was 26.5 (95% CI 24.7-28.5) per 1000 person-years for those who used metformin, compared with 36.3 (95% CI 34.2-38.6) per 1000 person-years for those who used sulfonylureas (HR 0.73, 95% CI 0.67-0.79). Results were consistent for kidney events alone (HR 0.73, 95% CI 0.59-0.91).
Metformin use for 361 days or longer after reaching an eGFR of less than 60 mL/min/1.73 m was associated with decreased likelihood of kidney events or death in patients with diabetes, compared with use of sulfonylureas. Metformin provided end-organ protection, in addition to glucose control.
糖尿病常导致肾脏疾病。本研究旨在评估在肾小球滤过率（eGFR）<60 mL/min/1.73 m 的同时伴有肾功能下降的糖尿病患者中，使用二甲双胍是否与死亡或肾脏事件相关。
我们利用退伍军人健康管理局、医疗保险和国家死亡指数数据库的数据，组建了一个全国性的回顾性队列，纳入 2001 年至 2016 年间使用二甲双胍或磺酰脲类药物的退伍军人，起始时 eGFR<60 mL/min/1.73 m。主要复合结局为肾脏事件（即 eGFR 下降 40%或终末期肾病）或死亡。次要结局为肾脏事件（eGFR 下降或终末期肾病）。我们使用倾向评分对队列进行加权，并使用 Cox 比例模型来估计结局和治疗中断的特定原因风险，治疗中断为竞争风险。我们将随访时间分为两个阶段，即随访开始后 360 天内和 361 天及以后。
在随访的前 360 天内，经倾向评分加权的队列包括 24883 例使用二甲双胍和 24998 例使用磺酰脲类药物的患者。使用二甲双胍或磺酰脲类药物的患者每 1000 人年的死亡或肾脏事件分别为 33.5（95%置信区间[CI]30.9-36.3）和 43.0（95% CI 40.1-46.0）（风险比[HR]0.78，95% CI 0.71-0.85）。对于肾脏事件的次要结局，HR 为 0.94（95% CI 0.67-1.33）。在 361 天以后的第二个时期，使用二甲双胍的患者主要结局事件发生率为每 1000 人年 26.5（95% CI 24.7-28.5），而使用磺酰脲类药物的患者为每 1000 人年 36.3（95% CI 34.2-38.6）（HR 0.73，95% CI 0.67-0.79）。对于肾脏事件单独发生的情况，结果也是一致的（HR 0.73，95% CI 0.59-0.91）。
在 eGFR<60 mL/min/1.73 m 的情况下，使用二甲双胍 361 天或更长时间与糖尿病患者的肾脏事件或死亡风险降低相关，与使用磺酰脲类药物相比。二甲双胍除了控制血糖外，还提供了器官保护作用。
