The Usefulness of Measuring the Anion Gap in Diagnosing Metformin-associated Lactic Acidosis

A Case Series

Jesus Ruiz-Ramos; Laura Lozano-Polo; Ana Juanes-Borrego; Iván Agra-Montava; Mireia Puig-Campmany; María Antonia Mangues-Bafalluy


J Med Case Reports. 2021;15(17) 

In This Article

Abstract and Introduction


Background: Metformin-associated lactic acidosis (MALA) is a widely documented adverse event of metformin. Despite being considered one of the main causes of metabolic acidosis, the association between an anion gap and MALA diagnosis is still uncertain.

Case Presentation: Cases involving six Caucasian patients with suspected MALA who were admitted to the emergency department were analysed. All these patients presented with pH values < 7.35, lactate levels > 2 mmol/L, and estimated glomerular filtration < 30 mL/min. Metformin plasma concentrations were > 2.5 mg/L in all the patients. The highest metformin concentrations were not found in the patients with the highest lactate levels. The anion gap values ranged from 12.3 to 39.3, with only two patients exhibiting values > 14.

Conclusions: In patients with MALA, there is a significant variability in the anion gap values, which is not related to the level of metformin accumulation, and therefore, it is doubtful whether measuring anion gaps is useful as an approach for MALA diagnosis.