Abstract
BackgroundTo evaluate whether metformin use assuredly alters overall all-cause death in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD).MethodsPubmed, Web of Science, Embase, and Cochrane Central Register of Controlled Trials were systematically searched from inception to Feb. 29, 2020 with no language restriction. All related articles comparing all-cause death of T2DM and CKD patients after metformin use (monotherapy or combination) versus non-metformin treatment were identified. Pooled risk ratios (RR) and 95% confidence intervals (CI) were computed using random-effects models regardless of the heterogeneity quantified by Cochrane χ2 and I2 statistics.ResultsTotally 13 studies (9 cohort studies [CSs], 3 subanalyses or post-hoc analyses of randomized controlled trials [RCTs], and 1 nested case-control article) involving 303,540 patients were included. Metformin-based treatments relative to any other measure displayed significantly lower risks of all-cause mortality (Pooled RRs 0.71, 95%CI 0.61 to 0.84; I2 = 79.0%) and cardiovascular events (Pooled RRs 0.76, 95%CI 0.60 to 0.97; I2 = 87.0%) in CKD patients at stage G1-3, with substantial heterogeneity. Metformin use was not significantly related with these end points in advanced CKD patients.ConclusionsMetformin use is connected with significantly less risks of all-cause mortality and cardiovascular events in patients with T2DM and mild/moderate CKD. However, RCTs with large sample sizes are warranted in the future to assess whether these key benefits extend to later stages of CKD by dose adjustment.
Highlights
Chronic kidney disease (CKD) is a global public health issue and gradually becomes more prevalent, mainly due to an increment in the diagnosis of type 2 diabetes mellitus (T2DM) [1, 2]
The search scheme was elaborated in Additional file 1 and the consistency with PRISMA Statement for reporting Systematic Review and Meta-analysis was illustrated in Additional file 2
Study Selection, Characteristics, and Quality Assessment initial search found 7,439 potentially feasible articles, and after title and abstract screening, 51 articles were retrieved for full-text assessment
Summary
Chronic kidney disease (CKD) is a global public health issue and gradually becomes more prevalent, mainly due to an increment in the diagnosis of type 2 diabetes mellitus (T2DM) [1, 2]. Two recent systematic reviews reported a lack of evidence that metformin relative to other antidiabetic drugs can raise the occurrence of lactic acidosis [8, 9]. Metformin intake decreased the all-cause deaths of moderate CKD patients [10], but this review had many limitations, including the lack of subgroup analysis, and ignorance of heterogeneity and publication bias. To evaluate whether metformin use assuredly alters overall all-cause death in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD)
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