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Nonhypoglycemic Effects of Thiazolidinediones

Akhil A. Parulkar, MD; Merri L. Pendergrass, MD, PhD; Ramona Granda-Ayala, MD; Tri Richard Lee, MD; and Vivian A. Fonseca, MD
[+] Article, Author, and Disclosure Information

From Tulane University Medical Center, New Orleans, Louisiana.

Disclosure: Dr. Fonseca has received research grants and honoraria from Parke-Davis, SmithKline Beecham, and Takeda-Lilly. Dr. Pendergrass has received research grants from Parke-Davis. Dr. Granda-Ayala has received research grants from SmithKline Beecham and Parke-Davis. These companies are manufacturers of drugs discussed in the article. However, no financial support was received from these companies for preparation of this article.

Acknowledgment: The authors thank Cherie McLain for help with the preparation of the manuscript.

Requests for Single Reprints: Vivian A. Fonseca, MD, Department of Medicine, Section of Endocrinology, Tulane University Medical Center SL53, 1430 Tulane Avenue, New Orleans, LA 70112-2699; e-mail, vfonseca@tulane.edu.

Current Author Addresses: Drs. Parulkar, Pendergrass, Granda-Ayala, and Fonseca: Department of Medicine, Section of Endocrinology, Tulane University Medical Center SL53, 1430 Tulane Avenue, New Orleans, LA 70112-2699.

Dr. Lee: 2727 West Holcombe Boulevard, Houston, TX 77025.

Ann Intern Med. 2001;134(1):61-71. doi:10.7326/0003-4819-134-1-200101020-00014
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The thiazolidinediones are a new class of compounds for treatment of type 2 diabetes. Troglitazone became available in the United States in 1997 but was withdrawn from the market in March 2000 because it caused severe idiosyncratic liver injury. Rosiglitazone and pioglitazone have been available since 1999. Because these drugs directly improve insulin resistance and decrease plasma insulin levels (a risk factor for coronary artery disease), they may decrease risk for cardiovascular disease in patients with type 2 diabetes. Research on the non–glucose lowering effects of troglitazone and, to a lesser extent, of rosiglitazone and pioglitazone have demonstrated changes in several cardiovascular risk factors associated with the insulin resistance syndrome. These beneficial effects include a decrease in blood pressure, correction of diabetic dyslipidemia, improvement of fibrinolysis, and decrease in carotid artery intima–media thickness. Other in vitro effects related to the ability of these agents to bind a newly described class of receptors (peroxisome proliferator–activated receptors) may also have implications for atherosclerosis. However, these drugs increase low-density lipoprotein (LDL) cholesterol levels and may favorably change LDL particle size and susceptibility to oxidation (although the implications of the latter changes are not clear). Furthermore, these drugs tend to cause weight gain. The authors' enthusiasm for these drugs has diminished somewhat because of reported adverse events, including rare liver failure. Nevertheless, because of the mechanism of action of the thiazolidinediones, clinical trials designed to determine whether they (or similar “insulin sensitizers“) decrease cardiovascular events in people with type 2 diabetes will be of interest.





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