Metformin-associated lactic acidosis


  • Acute and chronic use of metformin can lead to rare complication of Metformin-associated lactic acidosis (MALA)
  • Excreted (unmetabolized) in proximal tubules
  • Stimulates anaerobic glucose metabolism in splanchnic bed → increased lactate production
  • Inhibits mitochondrial respiratory chain → decreased gluconeogenesis from lactate → lactate accumulation
  • Associated with overdose, renal failure, liver disease, and septicemia[1]
  • Acidosis onset several hours after acute ingestion
  • Mortality rate 45%[2]
    • Lactate only predictive of mortality in overdose patients, not in incidental metformin accumulation
    • Elevated PT associated with increased mortality
    • pH >6.9, lactate >25 portends a poor prognosis[3]

Clinical Features

Differential Diagnosis

Lactic acidosis

By Type

  • Type A (tissue hypoperfusion)
  • Type B (decreased utilization)
  • Type D
    • episodes of encephalopathy and metabolic acidosis typically following high carbohydrate meals in patients with short bowel syndrome
    • metabolic acidosis and high serum anion gap, normal lactate level, short bowel syn or other forms of malabsorption, and characteristic neurologic findings
      • Type D lactate is not detected with standard lactate levels

Complete List



  • If intubated, maintain minute ventilation so as to not remove respiratory compensation for acidosis
  • Activated charcoal if peri-ingestion/mental status appropriate
  • Metformin should not cause hypoglycemia and, if present, should lead to work up of cause
  • Sodium Bicarbonate
    • No evidence to support its use in MALA patients[6]
  • Hemodialysis
    • Metformin can be cleared with hemodialysis and CVVH (continuous venovenous hemofiltration)[7]
      • Former preferred
      • CVVH should be used in unstable patient
    • Reduction in metformin levels following acute ingestion reported to require prolonged HD[8]
    • Consider if:
      • pH <7.1
      • Renal insufficiency
    • Mortality benefits mainly from improving acidosis than from removing Metformin

See Also


  1. Goldfrank, Lewis R. Goldfrank's Toxicologic Emergencies. 9th Ed. New York: McGraw-Hill, 2011
  2. Seidowsky, A., Nseir, S., Houdret, N., & Fourrier, F. (2009). Metformin-associated lactic acidosis: a prognostic and therapeutic study. Critical care medicine, 7, 2191–2196.
  3. Dell'Aglio, D. M., Perino, L. J., Kazzi, Z., Abramson, J., Schwartz, M. D., & Morgan, B. W. (2009). Acute metformin overdose: examining serum pH, lactate level, and metformin concentrations in survivors versus nonsurvivors: a systematic review of the literature. Annals of emergency medicine, 6, 818–823.
  4. Dodda V and Spiro P. Albuterol, an Uncommonly Recognized Culprit in Lactic Acidosis. Chest. 2011;140.
  5. . Zitek T, Cleveland N, Rahbar A, et al. Effect of nebulized albuterol on serum lactate and potassium in healthy subjects. Acad Emerg Med 2016;23:718–21.
  6. Kruse, J. A. (2001). Metformin-associated lactic acidosis. The Journal of emergency medicine, 3, 267–272.
  7. Barrueto, F., Meggs, W. J., & Barchman, M. J. (2002). Clearance of metformin by hemofiltration in overdose. Journal of toxicology. Clinical toxicology, 2, 177–180.
  8. Rifkin, S. I., McFarren, C., Juvvadi, R., & Weinstein, S. S. (2011). Prolonged hemodialysis for severe metformin intoxication. Renal failure, 4, 459–461.