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Is the use of metformin in patients undergoing dialysis hazardous for life? A systematic review of the safety of metformin in patients undergoing dialysis

Abstract

AIM: Metformin may have clinical benefits in dialysis patients, however its safety in this population is unknown. This systematic review evaluated the safety of metformin in dialysis patients. METHODS: MEDLINE, Embase, CENTRAL, PsycINFO and the Cochrane Library were searched for randomised controlled trials (RCTs) and observational studies evaluating metformin use in dialysis patients. Three authors reviewed the studies and extracted data. The primary outcomes were mortality, occurrence of lactic acidosis and myocardial infarction (MI) in patients taking metformin during dialysis treatment for >/=12 months ('long term'). Risk of bias was assessed using Risk Of Bias In Non-randomised Studies of Interventions (ROBINS-1). Overall quality of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS: Fifteen observational studies were eligible; seven were prospective observational studies and eight were case reports/case series. No randomised controlled trials were identified. The seven prospective observational studies [n=194] reported on cautious metformin use in patients undergoing maintenance dialysis. Only three provided long-term follow-up data. In two long-term studies of metformin therapy (</=1000 mg/day) in patients undergoing peritoneal dialysis (PD), one reported six deaths (6/83; 7%) due to major cardiovascular events (CVE) (three MI) and the other reported no deaths (0/35). One long-term study of metformin therapy (250 mg to 500 mg thrice weekly) in patients undergoing haemodialysis (HD) reported four deaths (4/61; 7%) due to major CVE (two MI). These findings provide very low quality evidence as they come from small observational studies. CONCLUSION: The evidence regarding the safety of metformin in people undergoing dialysis is inconclusive. Appropriately designed RCTs are needed to resolve this uncertainty.

Type Journal
ISBN 1365-2125 (Electronic) 0306-5251 (Linking)
Authors Abdel Shaheed, C.; Carland, J. E.; Graham, G. G.; Stocker, S. L.; Smith, G.; Hicks, M.; Williams, K. M.; Furlong, T.; MacDonald, P.; Greenfield, J. R.; Smith, F. C.; Chowdhury, G.; Day, R. O.
Responsible Garvan Author Prof Jerry Greenfield
Publisher Name Br J Clin Pharmacol
Published Date 2019-08-31
Status Published in-print
DOI 10.1111/bcp.14107
URL link to publisher's version https://www.ncbi.nlm.nih.gov/pubmed/31471973