Rational drug design and PPAR agonists.
Insulin resistance is a characteristic biological abnormality associated with type 2 diabetes, and is a key component of the metabolic syndrome, a condition in which an altered glucose control is associated with dyslipidemia, hypertension, and obesity. Thiazolidinediones (TZDs), a new class of oral drugs used for the treatment of type 2 diabetes, reduce insulin resistance via an action on peroxisome proliferator-activated receptors. Although the current use of TZDs is largely limited to the treatment of patients with diabetes, as recommended in the package insert, it is foreseeable that as the metabolic syndrome becomes a better understood clinical condition their use may be extended to the treatment of this cluster of disorders. The aim of the present article is to review the mechanism of action of TZDs, discuss the rationale for their use in the clinical setting, and provide an update on novel pharmacologic agents that, although not yet available for the treatment of diabetes, are likely to further enrich the repertoire of antidiabetic drugs in the very near future.
Perfetti
Riccardo
R
Department of Medical Sciences, Amgen Inc., One Amgen Center Drive, Mail Stop 38 3-A, Thousand Oaks, CA 91320-1799, USA. perfetti@amgen.com
D'Amico
Eugenio
E
D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D015195:Drug Design; D006801:Humans; D007004:Hypoglycemic Agents / Q000138:chemical synthesis / Q000627:therapeutic use*; D047495:PPAR gamma / Q000819:agonists*; D047492:Peroxisome Proliferator-Activated Receptors / Q000819:agonists*; D000077205:Pioglitazone; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000138:chemical synthesis / Q000627:therapeutic use*
D007004:Hypoglycemic Agents; D047495:PPAR gamma; D047492:Peroxisome Proliferator-Activated Receptors; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D000077205:Pioglitazone