FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Previous Volume 338:916-917 March 26, 1998 Number 13 Next

	Since this article has no abstract, we have provided an extract of the first 100 words of the full text and any section headings.

	Full Text Purchase this article Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited Related Article by Schwartz, S. PubMed Citation

To the Editor: Troglitazone is a thiazolidine 2,4-dione derivative that represents a novel class of oral drugs for the treatment of diabetes. In clinical trials, including two published in this issue of the Journal,^1,2 troglitazone has increased insulin action, enhanced oral glucose utilization, and improved dyslipidemia in patients with type II diabetes. Since its introduction in March 1997, more than 600,000 patients have received troglitazone in the United States and an additional 200,000 have received the drug in Japan.

Although troglitazone is effective in reducing hyperglycemia, concern has been raised by several reports of severe hepatic dysfunction leading to hepatic . . . [Full Text of this Article]

References

This article has been cited by other articles:

• Deng, X., Luyendyk, J. P., Ganey, P. E., Roth, R. A. (2009). Inflammatory Stress and Idiosyncratic Hepatotoxicity: Hints from Animal Models. Pharmacol. Rev. 61: 262-282 [Abstract] [Full Text]  
• Milam, J. E., Keshamouni, V. G., Phan, S. H., Hu, B., Gangireddy, S. R., Hogaboam, C. M., Standiford, T. J., Thannickal, V. J., Reddy, R. C. (2008). PPAR-{gamma} agonists inhibit profibrotic phenotypes in human lung fibroblasts and bleomycin-induced pulmonary fibrosis. Am. J. Physiol. Lung Cell. Mol. Physiol. 294: L891-L901 [Abstract] [Full Text]  
• Biserni, A., Giannessi, F., Sciarroni, A. F., Milazzo, F. M., Maggi, A., Ciana, P. (2008). In Vivo Imaging Reveals Selective Peroxisome Proliferator Activated Receptor Modulator Activity of the Synthetic Ligand 3-(1-(4-Chlorobenzyl)-3-t-butylthio-5-isopropylindol-2-yl)-2,2-dimethylpropanoic acid (MK-886). Mol. Pharmacol. 73: 1434-1443 [Abstract] [Full Text]  
• El-Naggar, M. H., Helmy, A., Moawad, M., Al-Omary, M., Al-Kadhi, Y., Habib, B. (2008). Late-Onset Rosiglitazone-Associated Acute Liver Failure in a Patient with Hodgkin's Lymphoma. The Annals of Pharmacotherapy 42: 713-718 [Abstract] [Full Text]  
• Ong, M. M.K., Latchoumycandane, C., Boelsterli, U. A. (2007). Troglitazone-Induced Hepatic Necrosis in an Animal Model of Silent Genetic Mitochondrial Abnormalities. Toxicol Sci 97: 205-213 [Abstract] [Full Text]  
• Kesselheim, A. S., Avorn, J. (2007). The Role of Litigation in Defining Drug Risks. JAMA 297: 308-311 [Full Text]  
• Peraza, M. A., Burdick, A. D., Marin, H. E., Gonzalez, F. J., Peters, J. M. (2006). The Toxicology of Ligands for Peroxisome Proliferator-Activated Receptors (PPAR). Toxicol Sci 90: 269-295 [Abstract] [Full Text]  
• Vansant, G., Pezzoli, P., Saiz, R., Birch, A., Duffy, C., Ferre, F., Monforte, J. (2006). Gene Expression Analysis of Troglitazone Reveals Its Impact on Multiple Pathways in Cell Culture: A Case for In Vitro Platforms Combined with Gene Expression Analysis for Early (Idiosyncratic) Toxicity Screening. International Journal of Toxicology 25: 85-94 [Abstract] [Full Text]  
• Navarro, V. J., Senior, J. R. (2006). Drug-Related Hepatotoxicity. NEJM 354: 731-739 [Full Text]  
• Gardner, O. S., Dewar, B. J., Graves, L. M. (2005). Activation of Mitogen-Activated Protein Kinases by Peroxisome Proliferator-Activated Receptor Ligands: An Example of Nongenomic Signaling. Mol. Pharmacol. 68: 933-941 [Abstract] [Full Text]  
• Baughman, T. M., Graham, R. A., Wells-Knecht, K., Silver, I. S., Tyler, L. O., Wells-Knecht, M., Zhao, Z. (2005). METABOLIC ACTIVATION OF PIOGLITAZONE IDENTIFIED FROM RAT AND HUMAN LIVER MICROSOMES AND FRESHLY ISOLATED HEPATOCYTES. Drug Metab. Dispos. 33: 733-738 [Abstract] [Full Text]  
• Maniratanachote, R., Minami, K., Katoh, M., Nakajima, M., Yokoi, T. (2005). Chaperone Proteins Involved in Troglitazone-Induced Toxicity in Human Hepatoma Cell Lines. Toxicol Sci 83: 293-302 [Abstract] [Full Text]  
• Watkins, P. B. (2005). Idiosyncratic Liver Injury: Challenges and Approaches. Toxicol Pathol 33: 1-5 [Abstract] [Full Text]  
• Brettenthaler, N., De Geyter, C., Huber, P. R., Keller, U. (2004). Effect of the Insulin Sensitizer Pioglitazone on Insulin Resistance, Hyperandrogenism, and Ovulatory Dysfunction in Women with Polycystic Ovary Syndrome. J. Clin. Endocrinol. Metab. 89: 3835-3840 [Abstract] [Full Text]  
• He, K., Talaat, R. E., Pool, W. F., Reily, M. D., Reed, J. E., Bridges, A. J., Woolf, T. F. (2004). METABOLIC ACTIVATION OF TROGLITAZONE: IDENTIFICATION OF A REACTIVE METABOLITE AND MECHANISMS INVOLVED. Drug Metab. Dispos. 32: 639-646 [Abstract] [Full Text]  
• He, K., Talaat, R. E., Woolf, T. F. (2004). INCORPORATION OF AN OXYGEN FROM WATER INTO TROGLITAZONE QUINONE BY CYTOCHROME P450 AND MYELOPEROXIDASE. Drug Metab. Dispos. 32: 442-446 [Abstract] [Full Text]  
• Cho, D.-H., Choi, Y. J., Jo, S. A., Jo, I. (2004). Nitric Oxide Production and Regulation of Endothelial Nitric-oxide Synthase Phosphorylation by Prolonged Treatment with Troglitazone: EVIDENCE FOR INVOLVEMENT OF PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR (PPAR) {gamma}-DEPENDENT AND PPAR{gamma}-INDEPENDENT SIGNALING PATHWAYS. J. Biol. Chem. 279: 2499-2506 [Abstract] [Full Text]  
• van Wijk, J. P.H., de Koning, E. J.P., Martens, E. P., Rabelink, T. J. (2003). Thiazolidinediones and Blood Lipids in Type 2 Diabetes. Arterioscler. Thromb. Vasc. Bio. 23: 1744-1749 [Abstract] [Full Text]  
• Winkler, K., Konrad, T., Fullert, S., Friedrich, I., Destani, R., Baumstark, M. W., Krebs, K., Wieland, H., Marz, W. (2003). Pioglitazone Reduces Atherogenic Dense LDL Particles in Nondiabetic Patients With Arterial Hypertension: A double-blind, placebo-controlled study. Diabetes Care 26: 2588-2594 [Abstract] [Full Text]  
• Gurnell, M., Savage, D. B., Chatterjee, V. K. K., O'Rahilly, S. (2003). The Metabolic Syndrome: Peroxisome Proliferator-Activated Receptor {gamma} and Its Therapeutic Modulation. J. Clin. Endocrinol. Metab. 88: 2412-2421 [Abstract] [Full Text]  
• Aroda, V. R., Henry, R. R. (2003). Thiazolidinediones: Potential Link Between Insulin Resistance and Cardiovascular Disease. Diabetes Spectr. 16: 120-125 [Abstract] [Full Text]  
• Chan, K. A., Truman, A., Gurwitz, J. H., Hurley, J. S., Martinson, B., Platt, R., Everhart, J. E., Moseley, R. H., Terrault, N., Ackerson, L., Selby, J. V. (2003). A Cohort Study of the Incidence of Serious Acute Liver Injury in Diabetic Patients Treated With Hypoglycemic Agents. Arch Intern Med 163: 728-734 [Abstract] [Full Text]  
• Studdert, D. M., Mello, M. M., Brennan, T. A. (2003). Medical Monitoring for Pharmaceutical Injuries: Tort Law for the Public's Health?. JAMA 289: 889-894 [Abstract] [Full Text]  
• Bae, M.-A., Song, B. J. (2003). Critical Role of c-Jun N-Terminal Protein Kinase Activation in Troglitazone-Induced Apoptosis of Human HepG2 Hepatoma Cells. Mol. Pharmacol. 63: 401-408 [Abstract] [Full Text]  
• Watanabe, Y., Nakajima, M., Yokoi, T. (2002). Troglitazone Glucuronidation in Human Liver and Intestine Microsomes: High Catalytic Activity of UGT1A8 and UGT1A10. Drug Metab. Dispos. 30: 1462-1469 [Abstract] [Full Text]  
• Kliewer, S. A., Goodwin, B., Willson, T. M. (2002). The Nuclear Pregnane X Receptor: A Key Regulator of Xenobiotic Metabolism. Endocr. Rev. 23: 687-702 [Abstract] [Full Text]  
• Honma, W., Shimada, M., Sasano, H., Ozawa, S., Miyata, M., Nagata, K., Ikeda, T., Yamazoe, Y. (2002). Phenol Sulfotransferase, ST1A3, as the Main Enzyme Catalyzing Sulfation of Troglitazone in Human Liver. Drug Metab. Dispos. 30: 944-949 [Abstract] [Full Text]  
• Lebovitz, H. E., Kreider, M., Freed, M. I. (2002). Evaluation of Liver Function in Type 2 Diabetic Patients During Clinical Trials: Evidence that rosiglitazone does not cause hepatic dysfunction. Diabetes Care 25: 815-821 [Abstract] [Full Text]  
• Toyoda, M, Takagi, H, Horiguchi, N, Kakizaki, S, Sato, K, Takayama, H, Mori, M (2002). A ligand for peroxisome proliferator activated receptor {gamma} inhibits cell growth and induces apoptosis in human liver cancer cells. Gut 50: 563-567 [Abstract] [Full Text]  
• Winkler, K., Friedrich, I., Baumstark, M. W, Wieland, H., Marz, W. (2002). Pioglitazone reduces atherogenic dense low density lipoprotein (LDL) particles in patients with type 2 diabetes mellitus. British Journal of Diabetes & Vascular Disease 2: 143-148 [Abstract]  
• Yamamoto, Y., Yamazaki, H., Ikeda, T., Watanabe, T., Iwabuchi, H., Nakajima, M., Yokoi, T. (2002). Formation of a Novel Quinone Epoxide Metabolite of Troglitazone with Cytotoxic to HepG2 Cells. Drug Metab. Dispos. 30: 155-160 [Abstract] [Full Text]  
• (2001). {blacktriangledown}Pioglitazone and {blacktriangledown}rosiglitazone for diabetes. DTB 39: 65-68 [Abstract] [Full Text]  
• Emoto, M., Anno, T., Sato, Y., Tanabe, K., Okuya, S., Tanizawa, Y., Matsutani, A., Oka, Y. (2001). Troglitazone Treatment Increases Plasma Vascular Endothelial Growth Factor in Diabetic Patients and Its mRNA in 3T3-L1 Adipocytes. Diabetes 50: 1166-1170 [Abstract] [Full Text]  
• Azziz, R., Ehrmann, D., Legro, R. S., Whitcomb, R. W., Hanley, R., Fereshetian, A. G., O’Keefe, M., Ghazzi, M. N. (2001). Troglitazone Improves Ovulation and Hirsutism in the Polycystic Ovary Syndrome: A Multicenter, Double Blind, Placebo-Controlled Trial. J. Clin. Endocrinol. Metab. 86: 1626-1632 [Abstract] [Full Text]  
• Tanaka, T., Kohno, H., Yoshitani, S.-i., Takashima, S., Okumura, A., Murakami, A., Hosokawa, M. (2001). Ligands for Peroxisome Proliferator-activated Receptors {{alpha}} and {{gamma}} Inhibit Chemically Induced Colitis and Formation of Aberrant Crypt Foci in Rats1. Cancer Res. 61: 2424-2428 [Abstract] [Full Text]  
• Lebovitz, H. E., Dole, J. F., Patwardhan, R., Rappaport, E. B., Freed, M. I. (2001). Rosiglitazone Monotherapy Is Effective in Patients with Type 2 Diabetes. J. Clin. Endocrinol. Metab. 86: 280-288 [Abstract] [Full Text]  
• Lenhard, M. J., Funk, W. B. (2001). Failure to Develop Hepatic Injury From Rosiglitazone in a Patient With a History of Troglitazone-Induced Hepatitis. Diabetes Care 24: 168-169 [Full Text]  
• Matthaei, S., Stumvoll, M., Kellerer, M., Häring, H.-U. (2000). Pathophysiology and Pharmacological Treatment of Insulin Resistance. Endocr. Rev. 21: 585-618 [Abstract] [Full Text]  
• Prendergast, K. A., Berg, C. L., Wisniewski, R. (2000). Troglitazone-Associated Hepatotoxicity Treated Successfully with Steroids. ANN INTERN MED 133: 751-751 [Full Text]  
• Takagi, T., Akasaka, T., Yamamuro, A., Honda, Y., Hozumi, T., Morioka, S., Yoshida, K. (2000). Troglitazone reduces neointimal tissue proliferation after coronary stent implantation in patients with non-insulin dependent diabetes mellitus: A serial intravascular ultrasound study. J Am Coll Cardiol 36: 1529-1535 [Abstract] [Full Text]  
• Kostrubsky, V. E., Sinclair, J. F., Ramachandran, V., Venkataramanan, R., Wen, Y. H., Kindt, E., Galchev, V., Rose, K., Sinz, M., Strom, S. C. (2000). The Role of Conjugation in Hepatotoxicity of Troglitazone in Human and Porcine Hepatocyte Cultures. Drug Metab. Dispos. 28: 1192-1197 [Abstract] [Full Text]  
• Hisatake, J.-i., Ikezoe, T., Carey, M., Holden, S., Tomoyasu, S., Koeffler, H. P. (2000). Down-Regulation of Prostate-specific Antigen Expression by Ligands for Peroxisome Proliferator-activated Receptor {{gamma}} in Human Prostate Cancer. Cancer Res. 60: 5494-5498 [Abstract] [Full Text]  
• Fürnsinn, C., Brunmair, B., Neschen, S., Roden, M., Waldhäusl, W. (2000). Troglitazone Directly Inhibits CO2 Production from Glucose and Palmitate in Isolated Rat Skeletal Muscle. J. Pharmacol. Exp. Ther. 293: 487-493 [Abstract] [Full Text]  
• Forman, L. M., Simmons, D. A., Diamond, R. H. (2000). Hepatic Failure in a Patient Taking Rosiglitazone. ANN INTERN MED 132: 118-121 [Abstract] [Full Text]  
• Al-Salman, J., Arjomand, H., Kemp, D. G., Mittal, M. (2000). Hepatocellular Injury in a Patient Receiving Rosiglitazone: A Case Report. ANN INTERN MED 132: 121-124 [Abstract] [Full Text]  
• Freid, J., Everitt, D., Boscia, J. (2000). Rosiglitazone and Hepatic Failure. ANN INTERN MED 132: 164-164 [Full Text]  
• Jones, S. A., Moore, L. B., Shenk, J. L., Wisely, G. B., Hamilton, G. A., McKee, D. D., Tomkinson, N. C. O., LeCluyse, E. L., Lambert, M. H., Willson, T. M., Kliewer, S. A., Moore, J. T. (2000). The Pregnane X Receptor: A Promiscuous Xenobiotic Receptor That Has Diverged during Evolution. Mol. Endocrinol. 14: 27-39 [Abstract] [Full Text]  
• Lurie, P., Sasich, L. D., Friedman, M. A., Woodcock, J., Lumpkin, M. M., Shuren, J. E., Hass, A. E., Thompson, L. J. (1999). Safety of FDA-Approved Drugs. JAMA 282: 2297-2298 [Full Text]  
• Yamazaki, H., Shibata, A., Suzuki, M., Nakajima, M., Shimada, N., Guengerich, F. P., Yokoi, T. (1999). Oxidation of Troglitazone to a Quinone-Type Metabolite Catalyzed by Cytochrome P-450 2C8 and P-450 3A4 in Human Liver Microsomes. Drug Metab. Dispos. 27: 1260-1266 [Abstract] [Full Text]  
• Ramachandran, V., Kostrubsky, V. E., Komoroski, B. J., Zhang, S., Dorko, K., Esplen, J. E., Strom, S. C., Venkataramanan, R. (1999). Troglitazone Increases Cytochrome P-450 3A Protein and Activity in Primary Cultures of Human Hepatocytes. Drug Metab. Dispos. 27: 1194-1199 [Abstract] [Full Text]  
• Mahler, R. J., Adler, M. L. (1999). Type 2 Diabetes Mellitus: Update on Diagnosis, Pathophysiology, and Treatment. J. Clin. Endocrinol. Metab. 84: 1165-1171 [Full Text]  
• Demetri, G. D., Fletcher, C. D. M., Mueller, E., Sarraf, P., Naujoks, R., Campbell, N., Spiegelman, B. M., Singer, S. (1999). Induction of solid tumor differentiation by the peroxisome proliferator-activated receptor-gamma ligand troglitazone in patients with liposarcoma. Proc. Natl. Acad. Sci. USA 96: 3951-3956 [Abstract] [Full Text]  
• Misbin, R. I. (1999). Troglitazone-Associated Hepatic Failure. ANN INTERN MED 130: 330-330 [Full Text]  
• Neuschwander-Tetri, B. A., Isley, W. L., Oki, J. C. (1999). Troglitazone-Associated Hepatic Failure. ANN INTERN MED 130: 330-330 [Full Text]  
• Koshida, H., Shibata, K., Kametani, T., Whitcomb, R. W. (1998). Pleuropulmonary Disease in a Man with Diabetes Who Was Treated with Troglitazone. NEJM 339: 1400-1400 [Full Text]  
• (1998). Troglitazone for Type 2 Diabetes. JWatch General 1998: 1-1 [Full Text]  
• Imura, H. (1998). A Novel Antidiabetic Drug, Troglitazone -- Reason for Hope and Concern. NEJM 338: 908-909 [Full Text]  
• Mueller, E., Smith, M., Sarraf, P., Kroll, T., Aiyer, A., Kaufman, D. S., Oh, W., Demetri, G., Figg, W. D., Zhou, X.-P., Eng, C., Spiegelman, B. M., Kantoff, P. W. (2000). Effects of ligand activation of peroxisome proliferator-activated receptor gamma in human prostate cancer. Proc. Natl. Acad. Sci. USA 97: 10990-10995 [Abstract] [Full Text]