These drugs bind and activate peroxisome proliferator-activated receptor-γ, a nuclear receptor present mainly in adipose tissue that regulates the expression of several genes involved in metabolism.
TZDs enhance the actions of endogenous insulin, partly directly (in the adipose cells) and partly indirectly (by altering release of 'adipokines' such as adiponectin and resistin which alter insulin sensitivity in the liver).
Plasma insulin concentrations are not increased and hypoglycaemia does not occur.