Thiazolidinediones: a new class of antidiabetic drugs

Abstract

Thiazolidinediones (TZDs) are a new class of oral antidiabetic agents. They selectively enhance or partially mimic certain actions of insulin, causing a slowly generated antihyperglycaemic effect in Type 2 (noninsulin dependent) diabetic patients. This is often accompanied by a reduction in circulating concentrations of insulin, triglycerides and nonesterified fatty acids. TZDs act additively with other types of oral antidiabetic agents (suphonylureas, metformin and acarbose) and reduce the insulin dosage required in insulin-treated patients. The glucose-lowering effect of TZDs is attributed to increased peripheral glucose disposal and decreased hepatic glucose output. This is achieved substantively by the activation of a specific nuclear receptor - the peroxisome proliferator-activated receptor-gamma (PPARgamma), which increases transcription of certain insulin-sensitive genes. To date one TZD, troglitazone, has been introduced into clinical use (in Japan, USA and UK in 1997). This was suspended after 2 months in the UK pending further investigation of adverse effects on liver function. TZDs have been shown to improve insulin sensitivity in a range of insulin-resistant states including obesity, impaired glucose tolerance (IGT) and polycystic ovary syndrome (PCOS). In Type 2 diabetes, the TZDs offer a new type of oral therapy to reduce insulin resistance and assist glycaemic control.