Metformin-Associated Lactic Acidosis (MALA)

Excerpt

Metformin is a biguanide compound used as first-line therapy for the treatment of diabetes mellitus and prevention of diabetic-related microvascular and macrovascular complications. It is also used to treat several other conditions, including polycystic ovary syndrome (PCOS), hyper-insular obesity, and weight gain from antipsychotic therapy. It is a derivative of Galega officinalis, also known as French lilac or goat’s rue. It was used as an herbal remedy in Medieval Europe and found in the 1920s to contain guanidine, an anti-hyperglycemic compound. Phenformin, metformin’s predecessor, was the first oral biguanide that was withdrawn from the market for a high incidence of fatal lactic acidosis.

Metformin exerts several physiologic actions directed at overall blood glucose reduction through insulin sensitization, antagonization of gluconeogenesis, and increasing intracellular glucose uptake. It has several notable side effects, including gastrointestinal symptoms (nausea, vomiting, and diarrhea), increased lactate production, reduced lactate clearance, and the potential to induce acidosis.

Metformin-associated lactic acidosis (MALA) is a rare complication of altered lactate and hydrogen metabolism defined as pH < 7.35 and lactate > 5.0 mmol/L in the setting of metformin use or overdose. Depending on the setting, it carries a mortality rate of up to 50%, which is correlated with worsening of acidosis and hyperlactatemia.