• Vol. 50 No. 2, 159–170
  • 01 February 2021

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

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ABSTRACT

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.


Diabetes is a chronic disease characterised by elevated levels of blood glucose. The most common type of diabetes is type 2 diabetes mellitus (T2DM). This usually occurs in adults and arises through insulin resistance or an insufficiency of insulin production. Diabetes is one of the priority non-communicable diseases targeted for action by world leaders. Its prevalence has been steadily increasing over the last few decades; the global prevalence of diabetes in the adult population has risen from 4.7% in 1980 to 8.5% in 2014. Chronic kidney disease (CKD) describes abnormal kidney function, abnormal kidney structure, or both. The severity of CKD can be determined by glomerular filtration rate and the presence of markers of kidney damage, such as albuminuria, urine sediment abnormalities, electrolyte abnormalities, abnormalities caused by tubular disease, structural abnormalities and abnormalities detected by histology.

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