The Glitazone Family of Antidiabetic Agents

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Abstract
In 1982, Takeda Inc. reported the discovery of ciglitazone (5-[4-(l­ methylcyclohexylmethoxy)-benzyl]thiazolidine-2,4-dione, ADD-3878), a compound which lowers blood glucose in animal models of Non Insulin Dependent Diabetes without an increase in insulin release, and which does not have an effect on the glycemia in normal animals. Since then many analogs have been produced, including troglitazone, pioglitazone, englitazone and darglitazone, and compounds where the thiazolidinedione ring has been replaced by other acidic moieties. Pharmacological studies have revealed effects on gluconeogenesis, glucose transport and glucose transporter expression, and a putative receptor in fat cells, PPARy, has been proposed. Clinical studies on troglitazone and darglitazone have shown these compounds to have glucose lowering effects, as well as effects on insulin sensitivity, lipid levels and blood pressure.

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