Hyperlactataemia and clinical severity of acute metformin overdose

Although metformin-associated lactic acidosis is well described, there is less information on metformin overdose and whether it is of similar severity.

This study aims to describe the clinical features, laboratory investigations and outcome of acute metformin overdoses.

Retrospective case series of acute metformin overdoses (> 3 g) admitted to a toxicology unit over 20 years. Cases were identified from a prospective database and data extracted included demographics, dose, coingestants, clinical effects, investigations, treatment and outcomes.

There were 36 acute metformin overdose cases. Median age 41 years old (15-68 years old); 25 were female. Median ingested dose was 10 g (interquartile range (IQR): 5-16.1 g; range: 3.5-50 g), with coingestants taken in 34 presentations. Gastrointestinal symptoms were present in 12/36, tachycardia in 10, bradycardia in three, hypotension in four and hypoglycaemia in eight. Hypotension and bradycardia were consistent with coingestants taken. Blood pH and lactate levels were available in 25/36. Median lowest pH was 7.35 (IQR: 7.28-7.38) and acidosis (pH < 7.35) occurred in 11/25. Median peak lactate was 3.9 mmol/L (IQR: 2.6-5.2 mmol/L). There was a statistical association between dose and lactate (r = 0.51; P = 0.01) and dose and pH (r = -0.70; P = 0.0001). Hyperlactataemia (lactate > 2 mmol/L) without acidosis occurred in 10/25, and hyperlactataemia with acidosis in 11/25; five had lactic acidosis. The median time to peak lactate in 10 presentations with peak lactate > 2 was 6 h (2-19 h). There were six intensive care unit admissions, one for lactic acidosis, and five related to coingestants. There were no deaths.

Metformin overdose is characterised by hyperlactataemia and minor gastrointestinal effects, with a few large ingestions progressing to lactic acidosis. Coingestants are common and may dominate toxicity.