Pharmacology (from AC1 drugs list):

Strategies

Improve Insulin sensitivity - Thiazolidinediones (Pioglitazone) - Increases insulin sensitivity in muscle and asipose tissue in T2DM

SE = weight gain, may lead to fluid retention, worsening heart failure, increase risk of bladder cancer

Increase endogenous insuline secretion - Sulphonylureas (Gliclazide) - Stimulates pancreatic insulin secretion from beta cells in T2DM.

Uses: Used in steroid induced hyperglycaemia due to its fast action

MOA: Sulphonylureas bind to the sulphonylurea receptor on the β-cell membrane, which closes ATP-sensitive potassium channels and blocks potassium efflux. The resulting depolarization promotes calcium influx and stimulates insulin release

Avoid in severe renal impairment

SE = weight gain, hypoglycaemia (severe is uncommon), hyponatreamia

Interactions = Warfarin, NSAIDS

Inhibit hepatic glucose production - Oral bigunide (metformin) - Inhibits hepatic glucuneogenesis and increases insulin sensitivity in T2DM

MOA - Activates AMP activated protein kinase

• SE
  • GI upset - diarrhoea is the most common SE
  • although rare, lactic acidosis is an important side effect. Alcohol further increases risk.
  • Hepatotoxic - Cannot be used in patients with an eGFR<30

Interactions = Diuretics, digoxin

Metformin

Targetting the function of Incretins

Incretin analogue - GLP-1 agonist (Exenatide) - Improves glucose control in T2DM