Metformin

Key points

• Metformin is in a class of drugs called biguanides and is used to treat type 2 diabetes.
• It lowers blood glucose by cutting glucose absorption from food and glucose output from the liver, and by increasing the body’s response to insulin.
• The label contraindicates metformin in patients with an estimated glomerular filtration rate below 30 mL/minute/1.73 m2, since the kidney is its main clearance route.

How the body clears metformin

Following an oral dose, about 90% of absorbed metformin leaves through the kidney within 24 hours, with a plasma elimination half-life of approximately 6.2 hours. The FDA label names the transport proteins that compete for that renal route: drugs that interfere with the organic cationic transporter-2 (OCT2) or multidrug and toxin extrusion (MATE) systems can raise metformin exposure and, with it, lactic acidosis risk.

The lactic acidosis boxed warning

Metformin’s label carries a boxed warning. Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension and resistant bradyarrhythmias. Onset is often subtle, marked by nonspecific symptoms such as malaise, muscle aches, breathing difficulty, drowsiness and abdominal pain. The label sets out the main risk factors: kidney impairment, interacting drugs such as topiramate, age 65 or older, an imaging procedure using injected contrast, surgery, low-oxygen states such as acute heart failure, heavy alcohol use, liver impairment and mitochondrial disease. If lactic acidosis is suspected, the label calls for immediate discontinuation of metformin and hospital-based supportive care, with prompt haemodialysis recommended.

A separate warning covers vitamin B12: a 29-week clinical trial recorded a drop to subnormal B12 levels in around 7% of patients, and the label asks prescribers to check haematological parameters yearly and vitamin B12 every two to three years.

Further reading

• METFORMIN HYDROCHLORIDE tablet, film coated
• Metformin: MedlinePlus Drug Information