Thiazolidinediones

Oral insulin sensitizing agents for the treatment of type 2 DM. Their use in recent years has declined due to concern for increased risk of new or worsening heart failure. Furthermore, questions have been raised about a possible association between TZD use and decreased bone mineral density and bladder cancer.

Hypoglycemia: Although these agents act primarily to sensitize peripheral tissues to insulin, TZDs carry a mild to moderate risk of hypoglycemia when combined with sulfonylureas or insulin.

Hepatotoxicity: The first marketed TZD, troglitazone, was removed from the market in USA and UK due to potentially severe liver dysfunction. Currently available TZDs have not shown this same effect on liver function, but liver function tests are still recommended before initiation and as clinically indicated.

CV risk: Associated with fluid retention and an increased risk of CHF. TZD administration has not been found to be an independent risk factor for myocardial infarction.

Precipitation of heart failure due to volume expansion and sodium retention.

Hypoglycemia when TZDs are used in conjunction with insulin and sulfonylureas.

Hyperglycemia, especially when TZDs are stopped in severe insulin resistance.