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

Metformin

inhibits mitochondrial glycerophosphate dehydrogenase, reducing hepatic gluconeogenesis;

also increases insulin sensitivity, enhances peripheral glucose uptake (by inducing the phosphorylation of GLUT4 enhancer factor), decreases fatty acid oxidation, and decreases absorption of glucose from the GI tract.

• Best initial drug
• No risk of hypoglycaemia
• Does not increase obesity

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)