Nephrology Division, Department of Medicine, NYU Langone Medical Center, New York, New York.
Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
Diabetes Obes Metab. 2019 May;21(5):1199-1208. doi: 10.1111/dom.13642. Epub 2019 Mar 4.
Metformin could have benefits on cardiovascular disease and kidney disease progression but is often withheld from individuals with diabetes and chronic kidney disease (CKD) because of a concern that it may increase the risk of lactic acidosis.
All-cause mortality, cardiovascular death, cardiovascular events (death, hospitalization for heart failure, myocardial infarction, stroke or myocardial ischemia), end stage renal disease (ESRD) and the kidney disease composite (ESRD or death) were compared in metformin users and non-users with diabetes and CKD enrolled in the Trial to Reduce Cardiovascular Events with Aranesp (darbepoeitin-alfa) Therapy (TREAT) (NCT00093015). Outcomes were compared after propensity matching of users and non-users and in multivariable proportional hazards models.
There were 591 individuals who used metformin at baseline and 3447 non-users. Among propensity-matched users, the crude incidence rate for mortality, cardiovascular mortality, cardiovascular events and the combined endpoint was lower in metformin users than in non-users, but ESRD was marginally higher (4.0% vs 3.6%). Metformin use was independently associated with a reduced risk of all-cause mortality (HR, 0.49; 95% CI, 0.36-0.69), cardiovascular death (HR, 0.49; 95% CI, 0.32-0.74), the cardiovascular composite (HR, 0.67, 95% CI, 0.51-0.88) and the kidney disease composite (HR, 0.77; 95% CI, 0.61-0.98). Associations with ESRD (HR, 1.01; 95% CI, 0.65-1.55) were not significant. Results were qualitatively similar in adjusted analyses of the full population. Two cases of lactic acidosis were observed.
Metformin may be safer for use in CKD than previously considered and may lower the risk of death and cardiovascular events in individuals with stage 3 CKD.
二甲双胍可能对心血管疾病和肾脏疾病的进展有益，但由于担心它可能会增加乳酸酸中毒的风险，因此经常不用于患有糖尿病和慢性肾脏病 (CKD) 的患者。
在接受阿那曲唑（darbepoeitin-alfa）治疗减少心血管事件试验（TREAT）（NCT00093015）的患有糖尿病和 CKD 的患者中，比较了使用二甲双胍和未使用二甲双胍的患者的全因死亡率、心血管死亡、心血管事件（死亡、心力衰竭住院、心肌梗死、中风或心肌缺血）、终末期肾病（ESRD）和肾脏疾病复合终点（ESRD 或死亡）。在对使用者和非使用者进行倾向匹配后，以及在多变量比例风险模型中比较了结果。
有 591 名患者在基线时使用了二甲双胍，3447 名患者未使用。在倾向匹配的使用者中，与非使用者相比，使用者的死亡率、心血管死亡率、心血管事件和联合终点的粗发生率较低，但 ESRD 略高（4.0%比 3.6%）。二甲双胍的使用与全因死亡率降低相关（HR，0.49；95%CI，0.36-0.69）、心血管死亡（HR，0.49；95%CI，0.32-0.74）、心血管复合终点（HR，0.67，95%CI，0.51-0.88）和肾脏疾病复合终点（HR，0.77；95%CI，0.61-0.98）。与 ESRD（HR，1.01；95%CI，0.65-1.55）的相关性不显著。在对全人群进行调整分析时，结果也是定性相似的。观察到两例乳酸酸中毒病例。
与之前的观点相比，二甲双胍在 CKD 中的使用可能更安全，并且可能降低 3 期 CKD 患者的死亡和心血管事件风险。
