Thiazolidinediones or glitazones (TZDs) are a relatively new category of antidiabetic drugs, which act by increasing the tissue’s sensitivity to insulin. Their administration does not cause hypoglycemia, and they present effects on other components of metabolic syndrome, such as dyslipidemia. Their efficacy increases when given with food, while the response to treatment may be delayed up to 4 weeks.
Indications: Administration of glitazones is indicated in patients with type 2 diabetes mellitus and, particularly in patients with insulin resistance. The medicines are given either as a monotherapy or in combination with a sulphonylureas or biguanides.
Mechanism of action: Glitazones bind to nuclear receptors, known as PPAR?, which activate the genes that play an important role in the metabolic effects of insulin. The main action of glitazones is the increase in glucose uptake in muscle cells and, secondly, the reduction in hepatic glucose production. Whether this action is direct or indirect due to the reduction in lipolysis in adipose tissue is not known.
In addition to reducing free fatty acids, they favor the functionality of ?-cells and possibly their survival, probably due to a decrease in glucotoxicity and lipotoxicity. Also, they improve dyslipidemia associated with diabetes, while also lowering blood pressure, accelerating fibrinolysis and improving endothelial function.
Because glitazones act through gene transcription, their therapeutic efficacy is not immediate but takes 2-8 weeks to appear. Also, like metformin, are effective only in the presence of insulin.
Side effects: Glitazones are generally well tolerated drugs. As a side effect, there is an increase of body weight similar to that of sulfonylureas. Peripheral edema may also occur in approximately 3% -5% of patients taking glitazones as a single agent and sometimes severe enough to require drug discontinuation, possibility that is increased when the use of the drug is combined with another hypoglycemic medication, especially insulin.
Another adverse reaction related to the use of thiazolidinediones, is anemia, which can be caused by hemolysis due to retention of sodium and water.
The most serious side effects of glitazones, is pulmonary edema and congestive heart failure which occur rarely in monotherapy treatments and increase in combination therapy with insulin. Studies have shown an increased risk of congestive heart failure in patients treated with pioglitazone. Although the frequency is relatively small.
FDA recommends a periodic measurement of liver enzymes, rosiglitazone and pioglitazone, unlike troglitazone, do not cause hepatic damage. Patients with severe liver disease should not take glitazones.
Absorption, distribution, elimination: Rosiglitazone and pioglitazone are rapidly absorbed from the intestine. In the circulation they are; 99% bound to plasma proteins. They are highly dependent on hepatic metabolism and are excreted in the urine and bile