Case of the month. Hepatic and renal failure in a patient taking troglitazone and metformin.

Troglitazone is a thiazolidinedione with insulin-sensitizing activities when administered to humans or animals with type 2 diabetes mellitus. It has been shown to have numerous desirable metabolic effects on glucose and lipid metabolism. A major adverse effect of troglitazone is the development of hepatotoxicity. In early clinical trials, elevations of serum aminotransferases (> 3 times upper normal limit) occurred in 48 of 2510 (1.9%) subjects receiving troglitazone. In December 1997 and again in August 1998, the United States Food and Drug Administration issued stronger warnings after getting reports of more than a hundred cases of liver damage, including liver failure requiring transplantation in three patients and death in another patient. Warner-Lambert Company announced on March 21, 2000 that it is voluntarily discontinuing the sale of Rezulin (troglitazone) tablets for the treatment of type 2 diabetes. Media reports sensationalizing the risks, associated with Rezulin therapy had created an environment in which patients and physicians were simply unable to make well-informed decisions regarding the safety and efficacy of Rezulin. Under these circumstances, and after discussions with the FDA, the company decided it was in the best interests of patients to discontinue marketing Rezulin. Concerns about the hepatotoxicity of troglitazone led the Medicine Control Agency of the United Kingdom to request voluntary withdrawal of the drug from the UK in December 1997.