Pioglitazone

Thiazolidinediones are a class of agents used in the treatment of type 2 diabetes mellitus. They are agonists to the PPAR-gamma receptor and reduce peripheral insulin resistance. Rosiglitazone was withdrawn in 2010 following concerns about the cardiovascular side-effect profile.

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)

Thiazolidinediones

(e.g. Rosiglitazone and Pioglitazone)

insulin sensitizers

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

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

Important genes that are upregulated by TZDs include:

• GLUT-4, in adipocytes and skeletal myocytes --> increases glucose uptake
• Another important one is the one that codes for adiponectin, a cytokine secreted by fat tissue that enhances insulin sensitivity and fatty acid oxidation.

Adiponectin levels are low in obese patients and those with type 2 diabetes.

N.B.