Metformin

Metformin (Glucophage®) is an anti-diabetic drug from the biguanide class (its other member is the withdrawn agent phenformin).

Uses

The main use for metformin is for the treatment of diabetes mellitus, especially when is concomitant obesity and insulin resistance. It is also being used increasingly in polycystic ovary syndrome (PCOS) and non-alcoholic steatohepatitis, two other diseases that feature insulin resistance.

Mode of action

Despite its therapeutic benefits, the actual mode of action of metformin is uncertain. A report from 2001 (Zhou G et al) indicated that it acts by activating AMP-activated protein kinase (AMPK) in liver cells, leading to increased fatty acid oxidation and glucose uptake by cells and decreased lipogenesis and hepatic glucose production. Its net effect in an improvement in insulin resistance.

Phenformin was withdrawn because of an increased risk of lactic acidosis (up to 60 cases per million patient-years). In recent studies it was revealed that, as long as it is not prescribed to patients who are at risk, metformin is much safer, and the risk of lactic acidosis approximates that of people who are not on the medication (Salpeter SR et al).

Contra-indications

Metformin should not be used in any condition that may increase the risk of lactic acidosis. This includes heart failure, kidney disorders, lung disease and liver disease.

History

The class of biguanide originates from the French lilac (Galega officinalis), a plant known for several centuries to improve the symptoms of diabetes mellitus.

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