ANALYSIS OF 30 CASE REPORTS OF ACUTE POISONING WITH METFORMIN DURING LONG-TERM THERAPY

Metformin is the gold-standard for the treatment of type 2 diabetes mellitus in overweight patients. Metformin displays a narrow therapeutic index and its pharmacokinetic profile may be modified by co-morbidities, possibly leading to intoxication. This study is a retrospective analysis of 30 metformin overdose cases. The main clinical outcomes were quantified according to the Poisoning Severity Score (PSS). Patient inclusion criteria were a metformin serum concentration greater than 2.3 mg/L during the study period of 9 months, and access to patient records. Of the 120 patients initially monitored for metformin levels, 41 had a serum concentration greater than 2.3 mg/L. Clinical and biological data were available for 30 of these patients; each was diabetic and under long-term metformin therapy. Ninety percent (n=27) of this cohort presented acute renal failure, secondary to dehydration, pre-existent heart failure decompensation, iatrogenic drug treatment or acido-ketotic coma. Twenty-nine patients (96.5%) suffered acidosis. All cases were serious (PSS >= 3) and one third of the patients died. No correlation could be established between the seriousness of the illnesses, death, serum metformin or plasma lactic acid levels. Twenty-eight patients (93.4%) presented at least one contraindication for metformin treatment at the time of their management. As a conclusion, we can affirm that lactic acidosis remains a severe complication under long-term metformin treatment. In most of the cases presented, intoxication occurred in diabetic patients who suddenly developed intercurrent illnesses that were responsible for high concentrations of metformin in the serum. This situation reenforces the necessity to respect contraindications and to increase awareness by physicians, pharmacists and patients alike.