SUBMITTED TO EVIDENCE-BASED MEDICINE

with type 2 diabetes and kidney disease: a systematic review. JAMA. 2014;312(24):2668-75. Commentary (799 words starting from context including references) Context Metformin is considered as the best initial pharmacological option to lower glucose concentrations in patients with type 2 diabetes mellitus (T2DM).1 As metformin may be combined with any other glucose-lowering therapy, a large majority of patients may receive metformin.1 However, because the drug is cleared by the kidneys, it may accumulate when renal function decreases, with the potential for exposure-dependent toxicity that could precipitate lactate accumulation. Chronic kidney disease (CKD) is a frequent scenario in T2DM, a condition that may challenge the use of many glucose-lowering agents.2 There is increasing evidence that the current cut-off points for renal safety of metformin in the U.S. may be overly restrictive.3 Consequently, a substantial number of patients may be deprived of using metformin although the drug might be beneficial to them.4 This systematic review examines the risk of metformin-associated lactic acidosis (MALA) i