eg. pioglitazone & roseglitazone and troglitazone.
Mechanism of action:
- Thiazolidinediones act to decrease insulin resistance. The overall effect is an enhancement of tissue sensitivity to insulin (that is a reduction in insulin resistance). Therefore the need of exogenous insulin is reduced.
- Their primary action is the nuclear regulation of genes involved in glucose and lipid metabolism and adipocyte differentiation.
- Tzds are ligands of peroxisome proliferator-activated receptor-gamma (PPAR-γ).
- They have a slow onset and offset of activity over weeks or even months.
These drugs are ‘insulin sensitizers’. They bind to a nuclear receptor (peroxisome proliferator activated receptor, PPAR), located mainly in adipose tissue, skeletal muscle and liver, which regulates the transcription of several insulin responsive genes.
Pharmacological actions
They act by increasing the member of GLUT4 glucose transportars in cell membrane of muscles and adipose tissue. ⇒ increases the uptake and utilization of glucose in these tissues.
- Clinical effect is not observed for 6 to 12 weeks.
Therapeutic uses
In combination with insulin, biguanides or sulfonylureas, in type II diabetes which exhibits insulin resistance.
Side effects:
- fluid retention, peripheral edema.
- weight gain.
- Hepatotoxicity
Contraindication:
- Pregnancy
- Liver Disease
- Heart Failure
- Type 1 DM