ENDO + REPRO: THIAZOLIDINEDIONES

Question 1

Thiazolidinediones: INDICATIONS

Answer 1

• Type 2 diabetes mellitus: As a single agent in overweight patients where metformin is contraindicated or not tolerated
• Added as a second agent to metformin or a sulphonylurea where blood glucose control is inadequate on one drug and the metformin/ sulphonylurea combination is contraindicated or not tolerated
• Added as a third agent with metformin and a sulphonylurea where blood glucose control is inadequate as an alternative to starting insulin

Question 2

Thiazolidinediones: MOA

Answer 2

• Insulin sensitisers
• They lower blood glucose by activating the gamma subclass of nuclear peroxisome proliferatoractivated receptors (PPARγ)
• This induces genes which enhance insulin action in skeletal muscle, adipose tissue and the liver, with increased peripheral glucose uptake and utilisation and reduced hepatic gluconeogenesis
• Do not stimulate pancreatic insulin secretion so do not cause hypoglycemia
• Can cause weight gain which can increase IR

Question 3

Thiazolidinediones: ADVERSE EFFECTS

Answer 3

• gastrointestinal upset, anaemia and minor neurological effects such as dizziness, headache and disturbed vision.
• More serious side effects include oedema and cardiac failure, particularly where pioglitazone is prescribed with insulin
• Associated with small increase in the risk of bladder cancer and an increase in bone fractures in women
• Idiosyncratic reactions include severe liver toxicity

Question 4

Thiazolidinediones: WARNINGS

Answer 4

• CI in heart failure, use with caution in patients with cardiovascular dx
• CI if there is known bladder cancer or macroscopic haematuria
• Used with caution inpatients with risk factors for bladder cancer (eg. smoking, occupational exposure, prior pelvic irradiation)
• Careful consideration should be given when prescribing pioglitazone for elderly patients who tend to have an increased risk of cardiac dx, bladder cancer, and bonef racture
• Use in caution in patients with hepatic impairment

Question 5

Thiazolidinediones: INTERACTIONS

Answer 5

• Pioglitazone combined with other antidiabetic drugs, increases the risk of adverse effects, e.g. hypoglycaemia and cardiac failure

Question 6

Thiazolidinediones: EXAMPLES

Answer 6

• Pioglitazone