piloglitazone

Mechanism of action

• Agonists of peroxisome proliferator-activated receptor gamma, which regulates genes involved in lipid and glucose metabolism.
• Increase the sensitivity of peripheral tissues to insulin; decrease hepatic glucose output

Indication

• Type 2 diabetes.

Side effects

• Commonly associated with peripheral oedema, weight gain, and anaemia.
• Pioglitazone use is associated with increased risk of heart failure and non-axial fractures in women and may increase the risk of bladder cancer.
• Pioglitazone may worsen heart failure and is contraindicated in NYHA class II–IV.
• Rarely, pioglitazone can cause raised liver enzymes and hepatocellular injury. They should not be used when aminotransferase level are > 2.5 times the upper limit of normal range.

Comments

• The only medicine in this class now available in Australian is piloglitazone.
• Thiazolidinediones reduce HbA1c by 0.5 to 1.4%. There is a lack of evidence that they improve diabetes-related complications and they are ineffective in up to 30% of patients.
• With the availability of safer alternatives, the main place of thiazolidinediones in managing type 2 diabetes is in patients with severe insulin resistance and/or when avoidance of hypoglycaemia is paramount (eg drivers of commercial vehicles). The potential treatment harms need to be considered, discussed with the patient and weighed against treatment benefits. This should be undertaken by an expert.