Thiazolidinediones are a class of agents used in the treatment of type 2 diabetes mellitus.

Mechanism of action

They are agonists to the PPAR-gamma receptor and reduce peripheral insulin resistance.

The PPAR-gamma receptor is an intracellular nuclear receptor. It's natural ligands are free fatty acids and it is thought to control adipocyte differentiation and function.

Adverse effects

  • Weight gain
  • Liver impairment: monitor LFTs
  • Fluid retention - therefore contraindicated in heart failure. The risk of fluid retention is increased if the patient also takes insulin
  • Recent studies have indicated an increased risk of fractures
  • Bladder cancer: recent studies have shown an increased risk of bladder cancer in patients taking pioglitazone (hazard ratio 2.64)