The phantom of lactic acidosis due to metformin in patients with diabetes

Metformin rarely, if ever, causes lactic acidosis when it is used as labeled. Metformin is associated with lactic acidosis in patients with conditions that can themselves cause lactic acidosis (heart failure, hypoxia, sepsis, etc.). But it is impossible to determine to what extent, if any, metformin may contribute to the development of lactic acidosis in any individual case. When metformin is used as labeled, the increased risk of lactic acidosis is either zero or so close to zero that it cannot be factored into ordinary clinical decision making. That metformin can itself cause lactic acidosis is supported by the finding of lactic acidosis in people who took overdoses. Thus, the accumulation of metformin in the setting of renal insufficiency might be expected to precipitate lactic acidosis in some patients who are at risk. If one excludes overdoses, most cases of metformin-associated lactic acidosis, particularly the fatal ones, were probably not caused by metformin.