UMEM Educational Pearls

Title: Metformin associated lactic acidosis (MALA): myth or reality?

Keywords: Metformin, lactic acidosis (PubMed Search)

Posted: 7/17/2014 by Hong Kim, MD, MPH
Click here to contact Hong Kim, MD, MPH

Metformin is the first line medication for the treatment of type II diabetes. A rare complication of chronic metformin use is MALA.

Incidence: 2-9 cases per 100,000 patients
Mortality: 30-50%

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).

Greater than 90% of metformin (unchanged) is eliminated by the kidney.

Metformin accumulation (from renal failure) leads to inhibition of complex I of the electron transport chain.^1,2

A case series of 66 patients MALA experienced severe lactic acidosis (pH: 6.91+ 0.18; lactate 14.36+ 4.9 mmol/L) and renal failure (Cr 7.24 + 3.29 mg/dL)³

Prodromal GI symptoms in 77%
Clinical findings at time of admission/presentation:
AMS/coma: 57%
Dyspnea/hyperventilation: 42%
Hemodynamic shock: 39%
Hypotension (SBP < 100 mmHg): 23%

No correlation between lactate and metformin level.

Risk factors
- Renal failure (metformin accumulation)
- Elderly population (higher mortality)
- Cardiac or respiratory insufficiency causing central hypoxia
- Sepsis/septic shock
- Liver disease
- IV contrast use (resulting in renal insufficiency)

Treatment: emergent hemodialysis

References

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.
Protti A et al. Metformin overdose, but not lactic acidosis per se, inhibits oxygen consumptions in pigs. Crit Care 2012;16:R75.
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.