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Metformin is one of the most commonly prescribed oral hypoglycemic agents. Metformin associated lactic acidosis (MALA) is uncommon but potentially life-threatening complication of metformin overdose.
Lactic acidosis occurs due to inhibition of mitochondrial glycerophosphate dehydrogenase, resulting in decreased conversion of lactic acid to pyruvate.
A small retrospective study (using Illinois Poison Center data) attempted to characterize the development of MALA after an acute overdose.
MALA was defined as
- Lactate: > 5 mmol/L
- Acidemia: (HCO3< 20 mmol/L or pH < 7.35)
Results
40 cases of MALA identified between Jan. 2001 to Dec. 2014
- Meadian age: 41 year
- Female: 55%
- Acute on chronic ingestion: 62.5%
- Hypoglycemia: 3 (7.5%)
Time to development of MALA (n=30)
- <=6 hours: 18 (60%)
- 6-12 hours: 9 (30%)
- >12 hours: 3 (10%)
- Unknown: 10
Death: 1 (2.5%)
Conclusion
- The majority of MALA developed within 6 hours. However, delayed onset of MALA can occur, up to 12 hours post ingestion.
- Minimum of 12 hour of observation is recommended after an acute metformin overdose.
References
Jillian Theobald, Jamie Schneider, Navneet Cheema & Carol DesLauriers (2019) "Time to development of metformin-associated lactic acidosis," Clinical Toxicology, DOI: 10.1080/15563650.2019.1686514