Troglitazone: Review and Assessment of Its Role in the Treatment of Patients with Impaired Glucose Tolerance and Diabetes Mellitus

Abstract

Troglitazone appears to be a safe, effective, and useful new agent in the treatment of insulin-requiring type 2 diabetes mellitus patients, although its HbA1C-lowering effects have been minimal in short-term trials, and its insulin dosage-reduction activity remains unclear. The Food and Drug Administration has also approved its use as monotherapy and in combination with sulfonylureas for patients with type 2 diabetes. It may have use in the treatment of patients with impaired glucose tolerance, but more clinical experience is needed before definitive conclusions can be made. The role of troglitazone therapy in diabetes mellitus and impaired glucose intolerance will continue to evolve as the results of studies and our clinical experience with this agent become available.

Impaired expression of the uncoupling protein-3 gene in skeletal muscle during lactation: fibrates and troglitazone reverse lactation-induced downregulation of the uncoupling protein-3 gene.

“…Moreover, it suggests that the PPAR-␥-dependent activation of the UCP-3 gene is not related to the physiological action of fatty acids promoting UCP-3 gene expression. Although PPAR-␥ is extremely low in skeletal muscle (12,33), chronic treatments of humans or rodents with troglitazone are known to improve insulin sensitivity and reduce triacylglyceride content in skeletal muscle (41). Several recent reports claim there is a direct effect of thiazolidinediones on this tissue (42,43), which would be consistent with the effects on the UCP-3 gene observed in this study.…”

Induction of differentiation and peroxisome proliferator-activated receptor ? expression in colon cancer cell lines by troglitazone

“…Ligands for PPARc include the natural prostanoid 15-deoxy-D 12,14 -prostaglandin J 2 , a variety of nonsteroidal anti-inflammatory drugs, and the thiazolidinedione class of anti-diabetic drugs (Forman et al 1995;Lehmann et al 1995;Johnson et al 1998). Troglitazone (TGZ), one of the thiazolidinediones, is used in the treatment of type 2 diabetes and is a potent and selective activator of PPARc (Willson et al 1996;Johnson et al 1998).…”

“…Troglitazone (TGZ), one of the thiazolidinediones, is used in the treatment of type 2 diabetes and is a potent and selective activator of PPARc (Willson et al 1996;Johnson et al 1998). These ligands have been shown to mediate negative effects on the proliferation of malignant tumor cells, such as liposarcoma and breast cancer cells (Tontonoz et al 1997;Mueller et al 1998), and also to induce differentiation of adipose tissue, urothelium, and colonic epithelial cells (Guan et al 1997;Sarraf et al 1998;Kitamura et al 1999;Lefebvre et al 1999;Rosen et al 1999), and apoptosis (Brockman et al 1998;Mueller et al 1998;Bishop-Bailey and Hla 1999;Yang and Frucht 2001).…”

Clinical Thiazolidinediones as PPARγ Ligands with the Potential for the Prevention of Cardiovascular Disease in Diabetes

“…TZDs are based on a parental chemical structure, thiazolidine-2,4-dione, with each of the clinically used agents, TRO, ROSI and PIO, possessing unique chemically modified side chains in their individual chemical structure to produce specific drug actions [36,55,56]. TZDs have a number of combined therapeutic effects including improvement of target cell response to insulin, glucose uptake and utilization in skeletal muscle and adipose tissue, are able to control hyperglycemia and reduce hyperinsulinemia without causing hypoglycemia, even at high doses [34-36, 57, 58].…”