二甲双胍与磺脲类药物治疗糖尿病和肾功能下降患者与主要不良心血管事件（MACE）的相关性，这一成果由美国退伍军人健康管理局-田纳西谷医疗系统老年病学研究教育临床中心Christianne L. Roumie团队取得。 2019年9月19日，《美国医学会杂志》在线发表了这一成果。

在这项回顾性队列研究中，研究组分析了2001-2016年间在美国退伍军人健康管理局接受治疗的退伍军人的临床资料。MACE包括急性心肌梗死、脑卒中、短暂性缺血发作或心血管死亡。

共有67749名二甲双胍和28976名磺酰脲持续单药治疗的患者。加权队列包括24679名二甲双胍治疗者和24799名磺脲类药物治疗者，中位年龄为70岁，其中98%为男性，82%为白人，平均肾小球滤过率为55.8/mL/min/1.73 m²，平均糖化血红蛋白水平为6.6%。

随访一年后，二甲双胍组中有1048例发生MACE事件，每1000人年23.0例，磺脲类药物组有1394例，每1000人年29.2例，特异性校正风险比为0.80，差异具有统计学意义。

总之，二甲双胍治疗糖尿病与肾功能下降的患者，与磺脲类药物相比，可显著降低发生MACE的风险。

Title: Association of Treatment With Metformin vs Sulfonylurea With Major Adverse Cardiovascular Events Among Patients With Diabetes and Reduced Kidney Function

Author: Christianne L. Roumie, Jonathan Chipman, Jea Young Min, Amber J. Hackstadt, Adriana M. Hung, Robert A. Greevy, Carlos G. Grijalva, Tom Elasy, Marie R. Griffin

Issue&Volume: 19 September 2019

Abstract: 

Importance  Before 2016, safety concerns limited metformin use in patients with kidney disease; however, the effectiveness of metformin on clinical outcomes in patients with reduced kidney function remains unknown.

Objective  To compare major adverse cardiovascular events (MACE) among patients with diabetes and reduced kidney function who continued treatment with metformin or a sulfonylurea.

Design, Setting, and Participants  Retrospective cohort study of US veterans receiving care within the national Veterans Health Administration, with data supplemented by linkage to Medicare, Medicaid, and National Death Index data from 2001 through 2016. There were 174?882 persistent new users of metformin and sulfonylureas who reached a reduced kidney function threshold (estimated glomerular filtration rate <60 mL/min/1.73 m2 or creatinine ≥1.4 mg/dL for women or ≥1.5 mg/dL for men). Patients were followed up from reduced kidney function threshold until MACE, treatment change, loss to follow-up, death, or study end (December 2016).

Exposures  New users of metformin or sulfonylurea monotherapy who continued treatment with their glucose-lowering medication after reaching reduced kidney function.

Main Outcomes and Measures  MACE included hospitalization for acute myocardial infarction, stroke, transient ischemic attack, or cardiovascular death. The analyses used propensity score weighting to compare the cause-specific hazard of MACE between treatments and estimate cumulative risk accounting for the competing risks of changing therapy or noncardiovascular death.

Results  There were 67?749 metformin and 28?976 sulfonylurea persistent monotherapy users; the weighted cohort included 24?679 metformin and 24?799 sulfonylurea users (median age, 70 years [interquartile range {IQR}, 62.8-77.8]; 48?497 men [98%]; and 40?476 white individuals [82%], with median estimated glomerular filtration rate of 55.8 mL/min/1.73 m2 [IQR, 51.6-58.2] and hemoglobin A1c level of 6.6% [IQR, 6.1%-7.2%] at cohort entry). During follow-up (median, 1.0 year for metformin vs 1.2 years for sulfonylurea), there were 1048 MACE outcomes (23.0 per 1000 person-years) among metformin users and 1394 events (29.2 per 1000 person-years) among sulfonylurea users. The cause-specific adjusted hazard ratio of MACE for metformin was 0.80 (95% CI, 0.75-0.86) compared with sulfonylureas, yielding an adjusted rate difference of 5.8 (95% CI, 4.1-7.3) fewer events per 1000 person-years of metformin use compared with sulfonylurea use.

Conclusions and Relevance  Among patients with diabetes and reduced kidney function persisting with monotherapy, treatment with metformin, compared with a sulfonylurea, was associated with a lower risk of MACE.

DOI: 10.1001/jama.2019.13206

Source: https://jamanetwork.com/journals/jama/fullarticle/2751397