Metformin use in patients with type 2 diabetes mellitus and chronic kidney disease: An evidence-based review.

INTRODUCTION: Practice guidelines advise caution on the use of metformin in patients with type 2 diabetes mellitus with chronic kidney disease (CKD). This review aims to examine the evidence for the benefits and risks of metformin use in patients with T2DM and CKD. METHODS: The Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials and PubMed were searched; the references of selected papers were hand searched. Systematic reviews, randomised controlled trials, cohort studies, case series and case-control studies were included. The full text of selected articles was reviewed. The outcomes studied were all-cause mortality, cardiovascular complications, lactic acidosis and worsening of renal function. Recommendations were graded according to the Scottish Intercollegiate Guidelines Network system. RESULTS: A total of 139 unique articles were identified, 14 of which met the inclusion criteria and were selected for full-text review. Four cohort studies reported an association between metformin use and improved all-cause mortality in CKD stage 4 and better. Two cohort studies reported improved cardiovascular outcomes with metformin use. Four cohort studies, 1 case series and 1 case-control study reported no significant association between metformin use and an increased risk of lactic acidosis in CKD. There is a moderate level of evidence to support reduced mortality, improved cardiovascular outcomes and a low risk of lactic acidosis with metformin use in patients with T2DM and with CKD stage 4 and above. CONCLUSION: Existing recommendations to restrict metformin use in diabetes patients with CKD need to be reviewed in light of emerging evidence supporting its overall benefits in these patients.