Metformin-related fatalities − The importance of combining forensic toxicology and postmortem biochemistry analyses in death involving antidiabetics

Abstract

Metformin is the most commonly used drug in the treatment of type 2 diabetes mellitus and appears as a promising drug for several other conditions. While generally well-tolerated and relatively safe, metformin can cause serious side effects, and intoxication cases have been reported. Classically, the severity of metformin intoxications is better assessed by measuring lactate blood concentration and/or blood pH than by directly determining blood drug concentration. However, such an approach is more complicated in postmortem investigation. Indeed, biochemistry changes occur after death, affecting both lactate concentration and pH. In this context, the authors report a case of a metformin-related fatality for which toxicological and biochemical analyses have been integrated in order to better understand pathophysiological mechanisms and/or circumstances surrounding such fatalities. Metformin was quantified in femoral blood (FB) (45 mg/L), heart blood (HB) (39 mg/L), urine (464 mg/L), vitreous (18 mg/L) and gastric content (202 mg/L) using liquid chromatography-tandem mass spectrometry (LC-MS/MS). β-hydroxybutyrate (BHB) was also quantified in FB (491 mg/L) and vitreous (473 mg/L) using LC-MS/MS. Vitreous sodium (122 mmol/L), chloride (102 mmol/L), glucose (<0.10 mmol/L), creatinine (277 µmol/L) and lactate (13 mmol/L) concentrations were determined in vitreous on an Atellica® CH 930 analyzer. Glycated hemoglobin (HbA1C) was assessed in FB (7.7 %) using a Tosoh® G8 HPLC analyser. Overall, only few cases of metformin-related fatalities have been described. Here, the metformin FB concentration appeared particularly high, in agreement with other reported cases. Similarly, the results of the postmortem biochemistry analysis were also consistent with those reported in other metformin-related fatalities. Interestingly, BHB concentrations were notably elevated in both FB and vitreous humor. Furthermore, creatinine was determined in vitreous humor at a particularly high concentration. This case highlights the importance of combining postmortem toxicological and biochemical analyses in deaths involving antidiabetics. Indeed, such fatalities are quite complex and both drug toxicity and metabolic disorders may overlap with regard to mechanisms of death.