Metformin toxicity

The drug metformin is useful in the treatment of patients with type 2 diabetes mellitus who are obese and whose hyperglycemia cannot be controlled by other agents. There are reports that some patients are predisposed to the toxic side effects of this drug, which include potentially fatal lactic acidosis. 

The most common toxic effects of metformin are gastrointestinal (anorexia, nausea, vomiting, abdominal discomfort, and diarrhea), which occur in up to 20% of patients. They are dose-related, tend to occur at the onset of therapy, and are often transient. However, metformin may have to be discontinued in 3-5% of patients because of persistent diarrhea. Absorption of vitamin B12 appears to be reduced during long-term metformin therapy, and annual screening of serum vitamin B12 levels and red blood cell parameters has been encouraged by the manufacturer to determine the need for vitamin B12 injections. In the absence of hypoxia or renal or hepatic insufficiency, lactic acidosis is less common with metformin therapy than with phenformin therapy. 

Metformin Obscure Reduced hepatic and renal gluconeogenesis Decreased endogenous glucose production Type 2 diabetes Oral maximal plasma concentration in 2-3 h Toxicity Gastrointestinal symptoms, lactic acidosis (rare) cannot use if impaired renal/hepatic function congestive heart failure (CHF), hypoxic/acidotic states, alcoholism... 

One week after starting to take metformin 850 mg in divided dose a 74-year-old man became confused and disoriented and had speech abnormalities and bilateral horizontal gaze-evoked nystagmus. Electroencephalography suggested a toxic-metabolic... 

A 48-year-old man successfully committed suicide with metformin and alcohol (133). The authors used a simplified, rapid, and sensitive HPLC assay, with no interference from other drugs or toxic substances,... 

Thiazolidinediones Pioglitazone (Actos) Rosiglitazone (Avandia) Similar to the biguanides (metformin) Headache dizziness fatigue/weakness back pain rare but potentially severe cases of hepatic toxicity... 

Avoid use of contrast dye while on metformin avoid renally toxic medications while on metformin Avoid use of cimetidine while taking metformin consider using ranitidine or famotidine... 

OCT Lamivudine Procainamide Meformin Trimethoprim Cimetidine Cimetidine f plasma exposure of lamivudine f procainamide toxicity f plasma exposure of metformin... 

The study [44] was initiated with two pharmacological treatment arms (metformin and trogUtazone) however, the hepatic toxicity of troglitazone resulted in a premature closure of that portion of the study. As discussed above, although metformin is unlikely to act by increasing insulin-stimulated glucose disposal, it is ofteu considered to be an insulin sensitizer, Be that as it may, the report of... 

Parenteral administration of iodinated contrast media to patients taking metformin may result in lactic acidosis. However, the problem is reported to occur only if the contrast media causes renal failure and metformin use is continued. This is because metformin is mainly excreted by the kidneys and in renal failure toxic levels may accumulate, which may result in lactic acidosis. A literature search identified 18 cases of lactic acidosis after the use of contrast media in patients taking metformin. Of these 18 cases, 14 or 15 were associated with pre-existing renal impairment and 2 cases with other contraindications to metformin (sepsis and cirrhosis). The remaining case was in an elderly woman with neurological disease. 

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