Metformin use in chronic kidney disease: new evidence to guide dosing

Abstract

Metformin controls blood glucose, does not cause hypoglycaemia or weight gain and has been shown to reduce the long-term complications of diabetes, including macrovascular disease.1 Since metformin is renally cleared, there is a genuine risk of metformin accumulation and associated lactic acidosis in chronic kidney disease (CKD). We have previously argued that there is disproportionate fear surrounding the safety of metformin in CKD, with important side effects from alternative agents ignored. Both the risk of hypoglycaemia with sulphonylureas or insulin and risk of heart failure with thiazoladinediones are expected to increase as CKD progresses, and are at least as large as the risk of lactic acidosis.2 Moreover, the mortality from metformin-induced (i.e. pure type B) lactic acidosis appears substantially smaller than the 50% observed with other more common causes of lactic acidosis.3 Nevertheless, the current UK’s National Institute for Clinical Excellence guidelines advise that metformin should be reviewed if the serum creatinine exceeds 130 µmol/l [or estimated GFR (eGFR) is below 45 ml/min/1.73 m2], and stopped when creatinine rises above 150 µmol/l (or eGFR falls below 30 ml/min/1.73 m2).4 Dosing recommendations from other bodies also advise a renal function threshold after which metformin becomes unsafe, but agreement is rare,5 with most not providing …