The H2-receptor antagonist cimetidine causes an increase in the plasma concentration of metformin, by reducing clearance of metformin by the kidneys; both metformin and cimetidine are cleared from the body by tubular secretion, and both, particularly the cationic (positively charged) form of cimetidine, may compete for the same transport mechanism. A small double-blind, randomized study found the antibiotic cefalexin to also increase metformin concentrations by a similar mechanism; theoretically, other cationic medications may produce the same effect.

Contraindications

Metformin is contraindicated in people with any condition that could increase the risk of lactic acidosis, including kidney disorders (creatinine levels over 150 µmol/l, although this is an arbitrary limit), lung disease and liver disease. Heart failure has long been considered a contraindication for metformin use, although a 2007 systematic review showed metformin to be the only anti-diabetic drug not associated with harm in people with heart failure.

It is recommended that metformin be temporarily discontinued before any radiographic study involving iodinated contrast (such as a contrast-enhanced CT scan or angiogram), as contrast dye may temporarily impair kidney function, indirectly leading to lactic acidosis by causing retention of metformin in the body. It is recommended that metformin be resumed after two days, assuming kidney function is normal.

Overdosage

A review of intentional and accidental metformin overdoses reported to Poison control centers over a 5-year period found that serious adverse events were rare, though elderly patients appeared to be at greater risk. Intentional overdoses with up to 63 g of metformin have been reported in the medical literature. The major potentially life-threatening complication of metformin overdose is lactic acidosis. Treatment of metformin overdose is generally supportive, but may include sodium bicarbonate to address acidosis and standard hemodialysis or continuous veno-venous hemofiltration to rapidly remove metformin and correct acidosis.