Insulin resistance is the major cause in Non Insulin Dependent Diabetes Mellitus (NIDDM). In this review insulin production from beta-cells and action of insulin is briefly described. Any intervention either in the production or action of insulin has been the leading cause of NIDDM. Therapeutic intervention to deal with the defective action of insulin at various receptor or target tissues has been outlined. Structure-activity relationship of a large number of thiazolidinediones, oxazolidinediones, isoxazolidinediones, biguanides, tetrazole derivatives, pyrazoles and pyrazolones, oxathiadiazole oxide, hydroxyurea and carboxylic acid derivatives have been described. The probable mechanism of action of these novel compounds through Peroxisome Proliferator-Activated Receptors that ameliorate the insulin resistance, has been described. Finally the clinical candidates at various stages of clinical evaluation have been compiled.
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