Thiazolidinediones belongs to novel oral antidiabetic (hypoglycemic) drugs. At present there are two thiazolidinediones available namely rosiglitazone and pioglitazone. Fat cells are the major site of action of thiazolidinediones.

Thiazolidinediones acts by selective agonism of “peroxisome proliferators activated receptor gamma”, which increases transcription of several insulin responsive genes. The genes cause reversal of insulin resistance by stimulation of GLUT4 (Glucose Transporter 4, which is the major glucose transporter in skeletal muscles) for expression and translocation, which improve entry of glucose to muscles and fat. The gluconeogenesis in liver is also suppressed by thiazolidinediones. There are also some other mechanisms involved in prevention of insulin resistance such as activation of genes which regulate fatty acid metabolism and lipogenesis in adipose tissues, increase in adipocyte (fat cells) turnover and differentiation etc.

The blood glucose lowering capacity of thiazolidinediones is less than that of sulfonylureas and metformin (biguanides), but due to improved control of blood glucose, the level of insulin and HbA1c (glycosylated hemoglobin) is reduced.

Pioglitazone increases HDL (High Density Lipoprotein or good cholesterol) level and lowers triglyceride level and generally have no effect in LDL (Low Density Lipoprotein or bad cholesterol) level in blood. The effects of rosiglitazone on lipid profile are not consistent.

Side effects of thiazolidinediones:

Both the thiazolidinediones (rosiglitazone and pioglitazone) are generally well tolerated. Minor side effects include headache, mild muscle pain expansion of plasma volume, edema, weight gain, anemia etc. Monotherapy with thiazolidinediones generally do not cause hypoglycemia. CHF (congestive heart failure) may be precipitated by thiazolidinediones. Liver function should be monitored closely during treatment with thiazolidinediones, as there are reports of some liver dysfunction. In addition rosiglitazone, can increase risk of bone fracture, especially in elderly women and pioglitazone may cause contraceptive failure in women.

Thiazolidinediones (rosiglitazone and pioglitazone) are contraindicated in liver disease and in CHF.

Therapeutic Uses of thiazolidinediones:

Thiazolidinediones are used in treatment of type-2 diabetes (not useful in type-1 diabetes), especially to supplement or as alternative to sulfonylureas and/or metformin. Thiazolidinediones reduce plasma glucose as well as HbA1c without increasing blood insulin level. Thiazolidinediones are also used in case of insulin resistance to overcome insulin resistance. Use of thiazolidinediones in type-2 diabetes can reduce mortality due to stroke or cardiovascular problem such as myocardial infarction.

Combined use of insulin and thiazolidinediones should be avoided as there are reports of precipitation of CHF with this combination. Thiazolidinediones also should not be used during pregnancy.

Thiazolidinediones can prevent development of type-2 diabetes among pre-diabetics, as seen in Diabetes Prevention Program, 2005.