Metformin Use and Risk of All-Cause Mortality and Cardiovascular Events in Patients With Chronic Kidney Disease-A Systematic Review and Meta-Analysis

Background To evaluate whether metformin use assuredly alters overall all-cause death in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). Methods Pubmed, 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 chi(2)and I(2)statistics. Results Totally 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; I(2 =)79.0%) and cardiovascular events (Pooled RRs 0.76, 95%CI 0.60 to 0.97; I(2 =)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. Conclusions Metformin 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.