14.01.4 Metformin

Despite the fact that metformin has been used in type 2 diabetes for many years, the mechanism of action is still not clear. We do know the pharmacodynamic actions that follow. Metformin inhibits gluconeogenesis, which is the conversion of amino acids to glucose in the liver. Metformin increases the sensitivity to insulin in type 2 diabetes, and where there is low sensitivity to insulin, this leads to increased glucose uptake. Metformin is orally active, and commonly used in the treatment of type 2 diabetes. Metformin is anti-hyperglycemic, it reduces hyperglycemia to normoglycemia. Metformin is not hypoglycemic i.e. it does not reduce normoglycemia to hypoglycemia. Thus, hypoglycemic adverse effects are rare with metformin. The most common unwanted effects of metformin are gastrointestinal disturbances, such as nausea and diarrhoea. Lactic acidosis is a rare, but often fatal, side effect that may occur when contraindications to its use are overlooked (e.g. kidney impairment). One advantage of metformin over some of the anti-diabetic drugs is that there is no weight gain with metformin. In contrast, insulin replacement therapy and the sulphonylureas commonly cause weight gain, which tends to make the diabetes worse.