Richardson Tadarro L, Hackstadt Amber J, Hung Adriana M, Greevy Robert A, Grijalva Carlos G, Griffin Marie R, Elasy Tom A, Roumie Christianne L
Veteran Administration Tennessee Valley VA Health Care System Geriatric Research Education Clinical Center (GRECC) Nashville TN.
Department of Medicine Vanderbilt University Medical Center Nashville TN.
J Am Heart Assoc. 2021 Apr 6;10(8):e019211. doi: 10.1161/JAHA.120.019211.
Background Metformin and sulfonylurea are commonly prescribed oral medications for type 2 diabetes mellitus. The association of metformin and sulfonylureas on heart failure outcomes in patients with reduced estimated glomerular filtration rate remains poorly understood. Methods and Results This retrospective cohort combined data from National Veterans Health Administration, Medicare, Medicaid, and the National Death Index. New users of metformin or sulfonylurea who reached an estimated glomerular filtration rate of 60 mL/min per 1.73 m or serum creatinine of 1.5 mg/dL and continued metformin or sulfonylurea were included. The primary outcome was hospitalization for heart failure. Echocardiogram reports were obtained to determine each patient's ejection fraction (EF) (reduced EF <40%; midrange EF 40%-49%; ≥50%). The primary analysis estimated the cause-specific hazard ratios for metformin versus sulfonylurea and estimated the cumulative incidence functions for heart failure hospitalization and competing events. The weighted cohort included 24 685 metformin users and 24 805 sulfonylurea users with reduced kidney function (median age 70 years, estimated glomerular filtration rate 55.8 mL/min per 1.73 m). The prevalence of underlying heart failure (12.1%) and cardiovascular disease (31.7%) was similar between groups. There were 16.9 (95% CI, 15.8-18.1) versus 20.7 (95% CI, 19.5-22.0) heart failure hospitalizations per 1000 person-years for metformin and sulfonylurea users, respectively, yielding a cause-specific hazard of 0.85 (95% CI, 0.78-0.93). Among heart failure hospitalizations, 44.5% did not have echocardiogram information available; 29.3% were categorized as reduced EF, 8.9% as midrange EF, and 17.2% as preserved EF. Heart failure hospitalization with reduced EF (hazard ratio, 0.79; 95% CI, 0.67-0.93) and unknown EF (hazard ratio, 0.84; 95% CI 0.74-96) were significantly lower in metformin versus sulfonylurea users. Conclusions Among patients with type 2 diabetes mellitus who developed worsening kidney function, persistent metformin compared with sulfonylurea use was associated with reduced heart failure hospitalization.
背景 二甲双胍和磺脲类药物是常用于治疗2型糖尿病的口服药物。对于估算肾小球滤过率降低的患者，二甲双胍和磺脲类药物与心力衰竭结局之间的关联仍了解甚少。
方法与结果 这项回顾性队列研究合并了来自美国退伍军人健康管理局、医疗保险、医疗补助和美国国家死亡索引的数据。纳入估算肾小球滤过率达到60 mL/（min·1.73 m²）或血清肌酐达到1.5 mg/dL并持续使用二甲双胍或磺脲类药物的新使用者。主要结局是因心力衰竭住院。获取超声心动图报告以确定每位患者的射血分数（EF）（射血分数降低<40%；中等射血分数40% - 49%；≥50%）。初步分析估算了二甲双胍与磺脲类药物的病因特异性风险比，并估算了心力衰竭住院和竞争性事件的累积发病率函数。加权队列包括24685名肾功能降低的二甲双胍使用者和24805名磺脲类药物使用者（中位年龄70岁，估算肾小球滤过率55.8 mL/（min·1.73 m²））。两组间潜在心力衰竭（12.1%）和心血管疾病（31.7%）的患病率相似。二甲双胍使用者和磺脲类药物使用者每1000人年的心力衰竭住院率分别为16.9（95%CI，15.8 - 18.1）和20.7（95%CI，19.5 - 22.0），病因特异性风险为0.85（95%CI，0.78 - 0.93）。在心力衰竭住院患者中，44.5%没有可用的超声心动图信息；29.3%被归类为射血分数降低，8.9%为中等射血分数，17.2%为射血分数保留。与磺脲类药物使用者相比，二甲双胍使用者中射血分数降低的心力衰竭住院（风险比，0.79；95%CI，0.67 - 0.93）和射血分数未知的心力衰竭住院（风险比，0.84；95%CI 0.74 - 0.96）显著更低。
结论 在肾功能恶化的2型糖尿病患者中，与使用磺脲类药物相比，持续使用二甲双胍与心力衰竭住院率降低相关。
