Fatal Metformin Intoxication with Markedly Elevated Blood and Liver Concentrations

Cantrell, F. Lee; Nelson, Craig; Gary, Ray D.; McIntyre, Iain M.

doi:10.1093/jat/bks076

Cited by 8 publications

(8 citation statements)

References 10 publications

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“…In Table 2, we have summarized the main clinical and postmortem findings (where available) in fatal cases related to therapeutic use or suicidal ingestion that we have collected upon literature review and the annual reports of the AAPCC from 2009 to 2011. Other fatal cases following therapeutic administration or suicidal use are mentioned in case series reports, but with limited available clinical and postmortem information [3,9,14,[17][18][19][20][21][22][23][24][25][26][27][28][29][30][31].…”

Section: Discussionmentioning

confidence: 99%

“…Based on the available data, metformin appears to be minimally susceptible to postmortem redistribution [17]. Blood levels ranging from 0.5 to 2.5 μg/ml are considered within the therapeutic range, whereas concentrations over 5 μg/ml are generally considered toxic [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31]. Lethal concentrations cannot be precisely defined.…”

Section: Discussionmentioning

confidence: 99%

“…Lethal concentrations cannot be precisely defined. Cantrell et al [17] described the case of a 57-year-old-woman with an antemortem blood metformin concentration of 210 mg/l and emphasized that the highest reported antemortem metformin concentration in which the patient survived was 165 mg/l, though other authors described antemortem metformin concentrations of up to 380 mg/l. Dell'Aglio et al [3] analyzed 22 cases of acute metformin overdose and observed that the mortality rate in patients with a peak serum metformin concentration of greater than 50 μg/ml was 38 %, with a median peak metformin level of 110 μg/ml in nonsurvivors.…”

Section: Discussionmentioning

confidence: 99%

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Fatal metformin overdose: case report and postmortem biochemistry contribution

et al. 2013

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Metformin is an oral antihyperglycemic agent used in the management of type 2 diabetes mellitus. Lactic acidosis from metformin overdose is a rare complication of metformin therapy and occurs infrequently with therapeutic use. Fatal cases, both accidental and intentional, are extremely rare in clinical practice. Metformin is eliminated by the kidneys, and impaired renal function can result in an increased plasma concentration of the drug. In this report, we describe an autopsy case involving a 70-year-old woman suffering from diabetes mellitus and impaired renal function who received metformin treatment. Metformin concentrations in the peripheral blood collected during hospitalization and femoral blood collected during autopsy were 42 and 47.3 µg/ml, respectively. Lactic acidosis (29.10 mmol/l) was objectified during hospitalization. Furthermore, postmortem biochemistry allowed ketoacidosis to be diagnosed (blood β-hydroxybutyrate, 10,500 µmol/l). Death was attributed to lactic acidosis due to metformin intoxication. Increased plasma concentrations of the drug were attributed to severely impaired renal function. The case emphasizes the usefulness of performing exhaustive toxicology and postmortem biochemistry towards the more complete understanding of the pathophysiological mechanisms that may be involved in the death process.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Fatal metformin overdose: case report and postmortem biochemistry contribution

et al. 2013

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“…Other studies have shown that metformin does not accumulate in the plasma nor in any tissues other than the intestine, even with repeated administration (35). However, these results are from animal studies, and there are little data available on metformin levels in human organs (36).…”

Section: Discussionmentioning

confidence: 96%

Metformin potentiates the anticancer effects of cisplatin under normoxic conditions in vitro

et al. 2014

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Metformin is a diabetes drug with anticancer properties. Several studies have investigated the effects of metformin combined with chemotherapeutic agents, with controversial results. This study evaluated the efficacy of combined metformin/cisplatin treatment in an endometrial cancer cell line. Ishikawa cells were treated with metformin, cisplatin or both types of treatment. Cell proliferation was evaluated by quantification and colorimetric and thymidine incorporation assays, cell cycle progression was assessed by flow cytometry, and apoptosis by the caspase-3 activity assay. The effects of metformin and cisplatin used in combination were assessed under normoxic (21% O2) and hypoxic (1% O2) conditions. Mitochondrial morphology was examined using the MitoTracker dye, while function was assayed by lactate production. Discrepant results were obtained from the different assays of cell proliferation, with the value obtained from the colorimetric assay being higher than that from cell counts after drug treatment. Combined treatment with metformin (≥2 mM) and cisplatin (1 µM) had additive anti-proliferative effects on cells under normoxic conditions. However, the additive effect of metformin was attenuated under hypoxia. Metformin caused morphological and functional changes in mitochondria, which appeared shortened after exposure to metformin, while the connections between individual mitochondria appeared weaker. Additionally, decreased MitoTracker staining was observed after an 8-h exposure to metformin. The colorimetric assay did not accurately determine the effects of metformin and cisplatin on cell proliferation. The additive effects of metformin on cisplatin-induced inhibition of cell proliferation were attenuated under hypoxic conditions, while metformin compromised mitochondrial structure and function. Additional studies are needed to determine the efficacy of this drug combination in vivo.

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“…Blood levels ranging from 0.5 to 2.5 μg/ml are considered within the therapeutic range, whereas concentrations over 5 μg/ml are generally considered toxic [15].…”

Section: Discussionmentioning

confidence: 99%

A Pediatric Suicide Attempt by Ingestion of Metformin, Glimepiride and Sulpiride: A Case Report and Literature Review

Gharsalli¹,

Kais²

2016

J Clinic Toxicol

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A case of a pediatric patient poisoning after ingestion of metformin, glimepiride and sulpiride, he was presented to the emergency service with symptoms and signs of hypoglycemia. Using a risk assessment based approach, the management of glimepiride and metformin overdose is discussed. Glimepiride overdose invariably results in profound hypoglycemia that requires resuscitation with IV dextrose and the use of octreotide as an antidote. Metformin overdose rarely causes problems. The acute sulpiride poisoning is poorly reported in the medical literature.Sulpiride toxicokinetic parameters such as t max = about 3 h, t 1/2=24.02 h, k(el)=0.029 h (-1) were also estimated. They have pointed

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Fatal Metformin Intoxication with Markedly Elevated Blood and Liver Concentrations

Cited by 8 publications

References 10 publications

Fatal metformin overdose: case report and postmortem biochemistry contribution

Fatal metformin overdose: case report and postmortem biochemistry contribution

Metformin potentiates the anticancer effects of cisplatin under normoxic conditions in vitro

A Pediatric Suicide Attempt by Ingestion of Metformin, Glimepiride and Sulpiride: A Case Report and Literature Review

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