Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Korea.
Diabetes Care. 2020 May;43(5):948-955. doi: 10.2337/dc19-0936. Epub 2020 Mar 4.
Metformin is the first pharmacological option for treating type 2 diabetes. However, the use of this drug is not recommended in individuals with impaired kidney function because of the perceived risk of lactic acidosis. We aimed to assess the efficacy and safety of metformin in patients with type 2 diabetic kidney disease (DKD).
We conducted a retrospective observational cohort study of 10,426 patients with type 2 DKD from two tertiary hospitals. The primary outcomes were all-cause mortality and end-stage renal disease (ESRD) progression. The secondary outcome was metformin-associated lactic acidosis. Taking into account the possibility that patients with less severe disease were prescribed metformin, propensity score matching (PSM) was conducted.
All-cause mortality and incident ESRD were lower in the metformin group according to the multivariate Cox analysis. Because the two groups had significantly different baseline characteristics, PSM was performed. After matching, metformin usage was still associated with lower all-cause mortality (adjusted hazard ratio [aHR] 0.65; 95% CI 0.57-0.73; < 0.001) and ESRD progression (aHR 0.67; 95% CI 0.58-0.77; < 0.001). Only one event of metformin-associated lactic acidosis was recorded. In both the original and PSM groups, metformin usage did not increase the risk of lactic acidosis events from all causes (aHR 0.92; 95% CI 0.668-1.276; = 0.629).
In the present retrospective study, metformin usage in advanced chronic kidney disease (CKD) patients, especially those with CKD 3B, decreased the risk of all-cause mortality and incident ESRD. Additionally, metformin did not increase the risk of lactic acidosis. However, considering the remaining biases even after PSM, further randomized controlled trials are needed to change real-world practice.
二甲双胍是治疗 2 型糖尿病的首选药物。然而，由于乳酸酸中毒的风险，肾功能受损的患者不建议使用该药。我们旨在评估二甲双胍在 2 型糖尿病肾病（DKD）患者中的疗效和安全性。
我们对来自两家三级医院的 10426 名 2 型 DKD 患者进行了回顾性观察队列研究。主要结局为全因死亡率和终末期肾脏疾病（ESRD）进展。次要结局为二甲双胍相关乳酸酸中毒。考虑到病情较轻的患者可能会开二甲双胍，因此进行了倾向评分匹配（PSM）。
根据多变量 Cox 分析，二甲双胍组的全因死亡率和 ESRD 发生率较低。由于两组的基线特征存在显著差异，因此进行了 PSM。匹配后，二甲双胍的使用仍与较低的全因死亡率（调整后的危险比[aHR]0.65；95%可信区间[CI]0.57-0.73；<0.001）和 ESRD 进展（aHR 0.67；95%CI 0.58-0.77；<0.001）相关。仅记录到 1 例二甲双胍相关乳酸酸中毒事件。在原始组和 PSM 组中，二甲双胍的使用并未增加所有原因导致的乳酸酸中毒事件的风险（aHR 0.92；95%CI 0.668-1.276；=0.629）。
在本回顾性研究中，在晚期慢性肾脏病（CKD）患者中，特别是 CKD 3B 患者中使用二甲双胍降低了全因死亡率和 ESRD 发生率的风险。此外，二甲双胍并未增加乳酸酸中毒的风险。然而，即使在 PSM 之后，仍然存在残余偏倚，需要进一步的随机对照试验来改变实际的治疗实践。
