Metformin in chronic kidney disease: time for a rethink.

Metformin has traditionally been regarded as contraindicated in chronic kidney disease (CKD), though guidelines in recent years have been relaxed to permit therapy if the glomerular filtration rate (GFR) is > 30 mL/min. The main problem is the perceived risk of lactic acidosis (LA). Epidemiological evidence suggests that this fear is disproportionate. Lactic acidosis is a rare complication to type 2 diabetes mellitus (T2DM), with an incidence of 6/100,000 patient-years. The risk is not increased in metformin-treated patients. Metformin possesses a number of clinical effects independent of glucose reduction, including weight loss, which are beneficial to patients. The risk of death and cardiovascular disease is reduced by about a third in non-CKD patients. Since metformin intoxication undoubtedly causes LA, and metformin is renally excreted, inappropriate dosage of metformin will increase the risk of LA. It is suggested that introduction of metformin therapy to more advanced stages of CKD may bring therapeutic benefits that outweigh the possible risks.