Severe metformin intoxication without development of lactic acidosis: clinical case

Abstract

Introduction. Metformin is the most widely used oral antidiabetic agent, belonging to the biguanide pharmacological group. Lactic acidosis associated with metformin is a rare event with an incidence of 19 cases per 100,000 patient-years. The risk of developing lactic acidosis when taking this drug is increased by several factors, such as age > 65 years; concomitant diseases that have the ability to induce hypoxemia (chronic kidney disease, congestive heart failure, cardiogenic shock, acute respiratory distress, sepsis, advanced liver disease, history of lactic acidosis); excessive alcohol consumption; and administration of iodinated contrast media. Case history. A 46-year-old man self-administered 50 metformin tablets at a dose of 500 mg each. Twelve hours after ingestion, he requested emergency medical assistance, presenting with the following symptoms: drowsiness, repeated vomiting, lethargy, and dizziness. The patient’s condition was assessed as serious, so he was admitted to the intensive care unit. The patient’s personal pathological history revealed the presence of comorbidities: type 2 diabetes mellitus, toxic liver cirrhosis, hypertension and chronic kidney disease. Paraclinical investigations revealed the presence of metabolic acidosis, but with lactate <5 mmol/l; progressive renal dysfunction with creatinine values in the first 24 hours up to 1184 µmol/l, urea – 34.5 mmol/l; severe hypoglycemia - 1.68 mmol/l; moderate cytolytic, cholestatic, inflammatory; hepatocellular insufficiency syndrome; coagulation disorders; and pancreatic dysfunction. Results and treatment. Since metformin is easily dialyzable, it was decided to promptly initiate intermittent hemodialysis. Fourteen hemodialysis sessions were performed, with a gradual reduction of creatinine to 112.1 µmol/l. Recurrent episodes of hypoglycemia were corrected with 40% glucose solution. Subsequently, hyperglycemia was resolved with insulin. Conclusions. Metformin should be used with caution in patients with concomitant pathologies. Metformin-induced lactic acidosis is potentially fatal. Early identification of metformin intoxication, with prompt initiation of renal replacement measures and dynamic monitoring of biochemical parameters, is essential.