Safety and effectiveness of metformin in patients with reduced renal function: a systematic review

Abstract

Aim To examine clinical and safety outcomes associated with metformin use in patients with impaired renal function. Materials and methods We searched PubMed and Embase databases from inception to August 2020, supplementing our search with a review of investigator files and reference lists of included studies. Any study reporting original data on metformin and patient-centred outcomes in patients with impaired renal function, defined as an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73m 2 , was included. Post hoc meta-analysis was performed for the outcomes of mortality, cardiovascular events and acidosis. Results Nine small prospective studies enrolling patients with significantly impaired renal function identified only one case of clinically apparent lactic acidosis. Among 13 larger retrospective studies, seven examined the risk of mortality across patient subgroups; meta-analysis showed reductions in overall mortality at an eGFR of 45 mL/min/1.73m 2 or higher but not at an eGFR of less than 45 mL/min/1.73m 2 . Eight retrospective studies evaluated acidosis as an outcome; meta-analysis showed no increase in risk of acidosis except at an eGFR of less than 30 mL/min/1.73m 2 , in which group the HR was 1.97 (95% CI 1.03-3.77). Conclusions The literature shows metformin to be associated with reduced mortality and no increased risk of acidosis at an eGFR of 45 mL/min/1.73m 2 or higher. Metformin appears to be associated with fewer benefits and possible in…