Lactic Acidosis Associated With Glucophage Use in a Man With Normal Renal and Hepatic Function

. Objective. Metformin has been associated with the serious side‐effect lactic acidosis. However, it remains unclear whether the use of metformin was a cause or a coincidence in lactic acidosis. Design. A literature search of the Index Medicus (1959–66) and of the databases Embase, Medline, Medline Express (1966–99) was performed using the keywords metformin, biguanides and lactic acidosis. All articles of cases with metformin‐induced lactic acidosis (MILA) were cross‐referenced. Subjects. Cases were included for analysis if they met the following criteria: serum pH ≤7.35, lactate concentration ≥5 mmol L−1. Intervention. A forum of six experts in intensive care medicine independently categorized the cases in MILA unlikely (score 0), possible MILA (score 1) or probable MILA (score 2). Main outcome measures. Statistical analysis included the paired interobserver agreement (κ) and multivariate regression analysis. Results. Of 80 reported cases, 33 were excluded because of insufficient quality. The forum scores of the remaining 47 cases were distributed normally with a mean score of 7 (range 2–10). The κ‐value was 0.041 (SD = 0.24, range −0.514, 0.427). Neither lactate concentration nor mortality correlated with serum metformin concentrations. Conclusions. Given the low interobserver agreement and the lack of any relationship between metformin levels and outcome parameters, the concept that there is a simple, causal relationship between metformin use and lactic acidosis in diabetic patients has to be reconsidered.

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“…A total of 37 articles were found, reporting 80 cases of lactic acidosis during metformin therapy[8, 9, 15–49].…”

Section: Resultsmentioning

confidence: 99%

Metformin and lactic acidosis: cause or coincidence? A review of case reports

Stades

Heikens

Erkelens

et al. 2004

Journal of Internal Medicine

168

115

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“…Lactic acidosis was defined according to the criteria of Luft[4]: arterial lactate > 5 mmol/l and blood pH ≤ 7.35. Metformin accumulation was defined on the grounds of plasma metformin concentration above normal (0.6 ± 0.5 mg/l)[2]. When these data were not available, the likelihood of metformin accumulation was estimated on the grounds of renal function.…”

Section: Methodsmentioning

confidence: 99%

Lactic acidosis in metformin therapy: searching for a link with metformin in reports of ‘metformin‐associated lactic acidosis’

Lalau

Race

2001

Diabetes Obesity Metabolism

116

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While the term 'metformin-associated lactic acidosis' is commonly used to depict all situations of lactic acidosis in metformin therapy, true metformin-associated lactic acidosis, i.e. one which refers to metformin and concurrent pathologies as co-precipitating factors, was never observed in the studied reports. As there was no mortality due to metformin alone, it is important that physicians are familiar with the range of other risk factors that contribute to lactic acidosis in patients treated with metformin.

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“…The second case involved a 58-year insulin-treated diabetic male with poorly controlled diabetes [121]. He was obese with a body mass index of 31.6 kg/m 2 .…”

Section: Casementioning

confidence: 99%