• Felicia Clara J H Tan, Seng Bin Ang, and Yong Mong Bee.
• Family Medicine Service, KK Women's and Children's Hospital, Singapore.
• Ann Acad Med Singap. 2021 Feb 1; 50 (2): 159-170.

IntroductionPractice 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.MethodsThe 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.ResultsA 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.ConclusionExisting 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.

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