Metformin is a biguanide used mainly in the treatment of type 2 diabetes mellitus. It has a number of actions which improves glucose tolerance (see below). Unlike sulphonylureas it does not cause hypoglycaemia and weight gain and is therefore first-line, particularly if the patient is overweight. Metformin is also used in polycystic ovarian syndrome and non-alcoholic fatty liver disease

Mechanism of action

• acts by activation of the AMP-activated protein kinase (AMPK)
• increases insulin sensitivity
• decreases hepatic gluconeogenesis
• may also reduce gastrointestinal absorption of carbohydrates

Adverse effects

• gastrointestinal upsets are common (nausea, anorexia, diarrhoea), intolerable in 20%
• reduced vitamin B12 absorption - rarely a clinical problem
• lactic acidosis with severe liver disease or renal failure
  • it is now increasingly recognised that lactic acidosis secondary to metformin is rare, although it remains important in the context of exams

Contraindications

• chronic kidney disease: NICE recommend that the dose should be reviewed if the creatinine is > 130 µmol/l (or eGFR < 45 ml/min) and stopped if the creatinine is > 150 µmol/l (or eGFR < 30 ml/min)
• metformin may cause lactic acidosis if taken during a period where there is tissue hypoxia. Examples include a recent myocardial infarction, sepsis, acute kidney injury and severe dehydration
• iodine-containing x-ray contrast media: examples include peripheral arterial angiography, coronary angiography, intravenous pyelography (IVP); there is an increasing risk of provoking renal impairment due to contrast nephropathy; metformin should be discontinued on the day of the procedure and for 48 hours thereafter
• alcohol abuse is a relative contraindication

Starting metformin