Title: Metformin associated lactic acidosis (MALA): myth or reality?<br/>Author: Hong Kim<br/><a href='http://umem.org/profiles/faculty/526/'>[Click to email author]</a><hr/><p>
Metformin is the first line medication for the treatment of type II diabetes. A rare complication of chronic metformin use is MALA.</p>
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Incidence: 2-9 cases per 100,000 patients</li>
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Mortality: 30-50%</li>
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The association between metformin accumulation and development of lactic acidosis is controversial as patients with suspected MALA experience concurrent illnesses such as sepsis/septic shock, tissue hypoxia, and/or organ dysfunction (especially renal failure).</p>
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Greater than 90% of metformin (unchanged) is eliminated by the kidney.</li>
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Metformin accumulation (from renal failure) leads to inhibition of complex I of the electron transport chain.<sup>1,2</sup></li>
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A case series of 66 patients MALA experienced severe lactic acidosis (pH: 6.91<u>+</u> 0.18; lactate 14.36<u>+</u> 4.9 mmol/L) and renal failure (Cr 7.24 <u>+</u> 3.29 mg/dL)<sup>3</sup></li>
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Prodromal GI symptoms in 77%</li>
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Clinical findings at time of admission/presentation:</li>
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AMS/coma: 57%</li>
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Dyspnea/hyperventilation: 42%</li>
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Hemodynamic shock: 39%</li>
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Hypotension (SBP <u><</u> 100 mmHg): 23%</li>
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No correlation between lactate and metformin level.</li>
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Risk factors
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Renal failure (metformin accumulation)</li>
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Elderly population (higher mortality)</li>
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Cardiac or respiratory insufficiency causing central hypoxia</li>
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Sepsis/septic shock</li>
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Liver disease</li>
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IV contrast use (resulting in renal insufficiency)</li>
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Treatment: emergent hemodialysis</li>
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<fieldset><legend>References</legend>
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Owens MR et al. Evidence that metformin exerts its anti-diabetic effects through inhibition of complex 1 of the mitochondrial respiratory chain. Biochem J. 2000;348;607-614.</li>
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Protti A et al. Metformin overdose, but not lactic acidosis per se, inhibits oxygen consumptions in pigs. Crit Care 2012;16:R75.</li>
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Vecchio S et al. Metformin accumulation: lactic acidosis and high plasmatic metformin levels in a retrospective case series of 66 patients on chronic therapy. Clin Toxicol 2014;52:129-135.</li>
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