Diabetes, metformin and lactic acidosis.

Objective: Metformin has long been thought to cause lactic acidosis (LA) but evidence from various sources has led researchers to question a direct causative relationship. We assessed the relationship of metformin prescription and other factors to the incidence of LA.

Methods: All cases of LA at a single hospital were identified from laboratory lactate measurements. We compared patients classified as Cohen and Woods class A and B, patients with and without diabetes, and those taking metformin or not.

Results: LA was more common than in published analyses based on hospital coding of diagnoses. The incidence of LA was greater in diabetes than in the nondiabetic population but with no further increase in patients taking metformin. Lactate levels were no greater in patients on metformin than in patients with type 2 diabetes not on metformin even if patients with acute cardiorespiratory disturbance (Cohen and Woods class A) were excluded. Acidosis was greater in diabetes (hydrogen ion 94·9 ± 4·6 vs 83·2 ± 2·3 10(-9) m, P = 0·027) but factors besides lactate contributed. Acute cardiorespiratory illness, acute renal impairment and sepsis were the most common of the recognized precipitating factors. Age (P = 0·01), acute renal failure (P = 0·015) and sepsis (P = 0·005) were associated with mortality.

Conclusions: Diabetes rather than metformin therapy is the major risk factor for the development of LA. Lactic acidosis occurs in association with acute illness particularly in diabetes. Current guidance for the prevention of lactic acidosis may overemphasize the role of metformin.