Selective PPAR modulators, dual and pan PPAR agonists: multimodal drugs for the treatment of type 2 diabetes and atherosclerosis.
More than 70% of patients with Type 2 diabetes mellitus (T2DM) die because of cardiovascular diseases. Current therapeutic strategies are based on separate treatment of insulin resistance and dyslipidaemia. Development of drugs with multimodal activities should improve management of the global cardiovascular risk of T2DM patients and result in better patient compliance. New therapeutic strategies are aimed at targeting the entire spectrum of dysfunctioning organs, cells and regulatory pathways implicated in the pathogenesis of T2DM, dyslipidaemia and atherosclerosis. PPAR family members play major roles in the regulation of lipid metabolism, glucose homeostasis and inflammatory processes, making these transcription factors ideal targets for therapeutic strategies against these diseases. This review discusses why PPARs and development of novel selective PPAR modulators, dual and pan PPAR agonists constitute promising approaches for the treatment of diabetes, dyslipidaemia and atherosclerosis.
Pourcet
Benoit
B
Institut Pasteur de Lille, Département d'Athérosclérose, 01 rue du Professeur Calmette, BP 245, Lille 59019, France.
Fruchart
Jean-Charles
JC
Staels
Bart
B
Glineur
Corine
C
D000818:Animals; D050197:Atherosclerosis / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D002317:Cardiovascular Agents / Q000494:pharmacology / Q000627:therapeutic use; D003131:Combined Modality Therapy / Q000379:methods; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D047492:Peroxisome Proliferator-Activated Receptors / Q000819:agonists* / Q000097:blood
D002317:Cardiovascular Agents; D007004:Hypoglycemic Agents; D047492:Peroxisome Proliferator-Activated Receptors