The Thiazolidinediones (also known as the '-glitazones') are a group of oral anti-diabetic drugs. They are second-line agents and can be used if Biguanides and Sulfonylureas are contraindicated or ineffective.
Drugs of this class are selective agonists of nuclear peroxisome proliferator-activated receptor gamma (PPAR-γ). Binding to this receptor ultimately influences the regulation of lipid and carbohydrate metabolism. As with the Biguanides the effects are dependent on the presence of insulin so these agents are unlikely to cause hypoglycaemia on their own.
The end result is peripheral sensitisation to insulin and decreased hepatic gluconeogenesis (production of glucose). Thialozidinediones may also enhance glucose uptake in the periphery by enhancing translocation of glucose transporters.
Drugs of this class include Rosiglitazone (proprietary name : Avandia) and Pioglitazone (Actos). A third drug, Troglitazone was withdrawn after severe liver toxicity was reported.
Liver function should be regularly checked in patients on Thiazolidinediones as liver toxicity may also rarely occur with newer agents. Other known side effects of the drugs include weight gain, raised HDL cholesterol, anaemia, fluid retention and oedema. Rosiglitazone has also been associated with an increased risk of Coronary Heart Disease. These agents should therefore be avoided in patients with known cardiovascular comorbidities.
Currently, Thiazolidinediones are approved for use only in Type 2
Diabetes Mellitus but there has been interest in their use for
HIV associated insulin resistance, hepatic
steatosis,
atherosclerotic disease and other conditions.
British National Formulary v.54
Brunton et al. Goodman & Gilman's The Pharmacological Basis of Therapeutics 11th edition.