• Be able to compare and contrast the PD of metformin and the sulfonoureas.
  1. Biguanide
  1. Main action is to reduce hepatic gluconeogenesis through activation of AMP-activated protein kinase.
  2. Importantly – this glucose lowering action does not depend on functioning pancreatic β-cells and therefore produces less hypoglycaemia.
  3. It is first line in treatment of T2DM because it is an insulin sparing agent and does not increase body weight or provoke hypoglycaemia.
  4. Because it inhibits hepatic gluconeogenesis, it therefore impairs hepatic metabolism of lactic acid.
  5. Major toxicity is severe lactic acidosis (dose related complication)
  6. Contraindications as follows:
    • Renal disease
    • Hepatic disease
    • Any condition leading to hypoxia (e.g. CCF) due to accumulation of lactic acid.
  1. Metformin is not plasma protein bound nor metabolized – it is excreted as the active compound by the kidney.
  2. T ½ of 1.5 to 3 hours.