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Troglitazone-Associated Hepatic Failure
- Brent A. Neuschwander-Tetri, MD;
- William L. Isley, MD; and
- Julie C. Oki, PharmD
- St. Louis University School of Medicine; St. Louis, MO 63110 (Neuschwander-Tetri) St. Lukes Hospital; Kansas City, MO 64111 (Isley) University of Missouri-Kansas City School of Medicine; Kansas City, MO 64108 (Oki)
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IN RESPONSE:
Dr. Misbin's update on troglitazone hepatotoxicity based on reports to the FDA is indeed worrisome. It would appear that some patients can experience an unpredictable yet fatal progression of liver disease well into the course of treatment. Delayed elevation of liver enzyme levels was noted in the initial published review of the clinical trials data (1), yet the analysis of this relatively small and well-controlled initial experience led to the conclusion that the enzyme changes were uniformly reversible (2). If minor elevations in ALT levels (<3 times the upper limit of normal) can be a harbinger of liver failure in some patients, as suggested by the experience reported by Dr. Misbin, then a little more fear and attentiveness are needed on the part of all prescribers than was suggested by the early conclusions (2). The erratic progression of liver disease documented by this case and the observation that continued hepatocellular injury can progress even weeks after discontinuation of troglitazone therapy only re-emphasizes the need to closely follow all patients treated with this drug for the development of any liver enzyme abnormalities well into the course of treatment.
Furthermore, in light of the recent publication of the UK Prospective Diabetes Study showing reduction in microvascular disease and no increase in macrovascular disease with sulfonylurea or insulin therapy (3), one must question the utility of monotherapy with a drug (troglitazone) that induces less improvement in glycemia than these established therapies (4) and seems to have a problematic risk–benefit ratio and a high cost (drug acquisition and liver test monitoring)-benefit ratio. We believe that troglitazone's major clinical utility is in combination with insulin (5) in patients whose diabetes is poorly controlled by other therapies.
Brent A. Neuschwander-Tetri, MD
St. Louis University School of Medicine; St. Louis, MO 63110
Julie C. Oki, PharmD
University of Missouri-Kansas City School of Medicine; Kansas City, MO 64108
The Editors welcome submissions for possible publication in the Letters section. Authors of letters should:
•Include no more than 300 words of text, three authors, and five references
•Type with double-spacing
•Send three copies of the letter, an authors' form signed by all authors, and a cover letter describing any conflicts of interest related to the contents of the letter.
Letters commenting on an Annals article will be considered if they are received within 6 weeks of the time the article was published. Only some of the letters received can be published. Published letters are edited and may be shortened; tables and figures are included only selectively. Authors will be notified that the letter has been received. If the letter is selected for publication, the author will be notified about 3 weeks before the publication date. Unpublished letters cannot be returned.
Annals welcomes electronically submitted letters.
- Copyright ©2004 by the American College of Physicians
