METFORMIN QUICK HITS:
- decreases insulin resistance,
- decreases hepatic glucose output,
- increases glucose uptake peripherally
- Decreases fasting BG 20-40%.
The major toxic effect of metformin is lactic acidosis.
It causes glucose to be converted to lactate in the small intestines, and decreases gluconeogenesis from lactate– and pyruvate and alanine- increasing LA and substrates that can get converted to LA.
its RARE: Only 5.1 cases per 100,000 patient yrs of lactic acidosis in non-comorbitiy (renal or liver disease) patients.
However in patients that do develop LA, there is a mortality of 45%. These deaths were speculated to be related to comorbid conditions, rather than the levels of metformin in their blood. Most accurate predictor was liver function.
Lactic acidosis likely to occur in patients with renal insufficiency (Cr above 1.4/1.5), liver or ETOH disease, HF, history of prior LA, hypoxic states, hemodynamic instability.
- consider bicarb if pH < 7.1, otherwise may cause electrolyte abnormalities.
- Patients with severe renal insufficiency or are simply very sick require emergent HD.
Submitted by J. Rothstein.
References: Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus. Salpeter S, Greyber E, Pasternak G, Salpeter E, Cochrane Database Syst Rev. 2006; uptodate.com: metformin poisoning; Metformin. AU Bailey CJ, Turner RC SO, N Engl J Med. 1996;334(9):574. picture