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Another Thiazolidinedione Can Cause Liver Injury

A 49-year-old man with diabetes suffers liver damage after taking pioglitazone for 6 months.

Thiazolidinediones, which are used to treat type 2 diabetes, can cause liver injury, but newer agents in this class are thought to confer less risk. Now, physicians report a second case of hepatotoxicity that has been associated with the newest thiazolidinedione, pioglitazone.

Metformin and, then, pioglitazone were added to the treatment regimen of a 49-year-old diabetic man who was already taking glyburide. After 4.5 months of taking pioglitazone, he developed anorexia, nausea, and abdominal discomfort. Liver enzyme tests were normal, glucose was elevated, and the dose of pioglitazone was increased to 45 mg daily. After 6 months of pioglitazone treatment, he developed icterus, hyperbilirubinemia, an elevated alkaline phosphatase level, and aminotransferase levels that were about 14 times higher than the normal range. Liver biopsy revealed a mixed hepatocellular-cholestatic type of liver injury -- cholestasis, portal inflammation, and bile-duct injury -- consistent with drug hepatotoxicity. The patient continued taking all medications except pioglitazone: 6 weeks later, liver chemistry had returned to normal, and symptoms had resolved.

Comment: The release of each new thiazolidinedione has held the promise that liver injury might not be an issue. This case report suggests that all thiazolidinediones currently available for clinical use can cause serious liver damage. Therefore, although risk may have been greater with troglitazone, patients who take rosiglitazone or pioglitazone should have liver enzymes checked periodically.

— Richard Saitz MD, MPH

Published in Journal Watch General Medicine March 26, 2002

Citation(s):

May LD et al. Mixed hepatocellular-cholestatic liver injury after pioglitazone therapy. Ann Intern Med 2002 Mar 19; 136:449-52.

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