Thiazolidinediones (glitazones) Flashcards
Give 2 examples of glitazones
- Pioglitazone
- Rosiglitazone
What is the mechanism of action of glitazones?
Result in binding of a PPARy-complex to DNA, which causes transcription of genes whose products are involved in insulin signalling. Tissues also become more sensitive to insulin by recruiting glucose transports to cell surfaces. This reduces peripheral insulin resistance, leading to a reduction of blood glucose concentration
Are glitazones effective without insulin?
No
What is the result of glitazones only being effective in the presence of insulin?
They can only be used in patients who have endogenous insulin production or who inject insulin
What is the route of delivery of glitazones?
PO
What are the indications for glitazones?
Used in type 2 diabetes mellitus in the following ways;
- Single therapy
- Dual therapy
- Triple therapy
How are glitazones used in single therapy?
In overweight diabetic patients who cannot take metformin (contraindicated or not tolerated)
How are glitazones used in dual therapy?
With metformin or a sulphonylurea, when blood glucose control is not achieved with one drug and metformin and sulphonylurea
How are glitazones used in triple therapy?
With metformin and sulphonylurea, when blood glucose control is inadequate (an alternative to starting insulin)
When should you avoid prescribing glitazones?
- History of heart failure
- Previous or active bladder cancer and uninvestigated macroscopic haematuria
- Pregnancy and breastfeeding
- Hepatic impairment
- Patients receiving dialysis
Why should you avoid prescribing glitazones in patients with a history of heart failure?
There are concerns about increased incidence of heart failure in patients who take pioglitazones combined with insulin, particularly in those with cardiovascular risk factors - such patients require monitoring for signs of heart failure
Why should you avoid prescribing glitazones in previous or active bladder cancer, and uninvestigated macroscopic haematuria?
There is a small increased risk of bladder cancer in patients who take a pioglitazone
Why should glitazones be used with caution in the elderly?
Increased risk of fractures
What should be done before starting pioglitazone?
Assess patient for risk factors of bladder cancer and investigate any unexplained haematuria
What monitoring is required with glitazones?
- Monitor closely for signs of heart failure, especially in patients with a history of cardiovascular disease
- Check LFTs at baseline then every 2-6 months
