Investigational PPAR-gamma agonists for the treatment of Type 2 diabetes.
The tremendous increase in the global prevalence of Type 2 diabetes (T2D) and its conglomeration of metabolic disorders has dramatically intensified the search for innovative therapies to fight this emerging epidemic. Over the last decade, the family of nuclear receptors, especially the peroxisome proliferator-activated receptors (PPARs), has emerged as one of the most important drug targets aimed at combating the metabolic syndrome. Consequently, compounds that activate the PPARs have served as potential therapeutics for the treatment of T2D and the metabolic anomalies associated with this disorder. This review focuses on the currently marketed compounds and also describes the discovery and development of the next generation of PPAR ligands that are under investigation for the potential treatment of T2D and the metabolic syndrome.
Savkur
Rajesh S
RS
Eli Lilly and Company, Diabetes Research, Lilly Research Laboratories, Indianapolis, IN 46285, USA.
Miller
Anne R
AR
D017667:Adipocytes / Q000378:metabolism; D000818:Animals; D002318:Cardiovascular Diseases / Q000139:chemically induced; D002986:Clinical Trials as Topic; D006224:Cricetinae; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D015507:Drugs, Investigational / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity; D050171:Dyslipidemias / Q000188:drug therapy; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000960:Hypolipidemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects; D024821:Metabolic Syndrome / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D032342:Muscle Cells / Q000378:metabolism; D009928:Organ Specificity; D047493:PPAR alpha / Q000819:agonists; D047494:PPAR delta / Q000819:agonists / Q000502:physiology; D047495:PPAR gamma / Q000819:agonists* / Q000737:chemistry / Q000502:physiology; D020033:Protein Isoforms / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011924:Rats, Zucker; D015430:Weight Gain / Q000187:drug effects
D015507:Drugs, Investigational; D007004:Hypoglycemic Agents; D000960:Hypolipidemic Agents; D007328:Insulin; D047493:PPAR alpha; D047494:PPAR delta; D047495:PPAR gamma; D020033:Protein Isoforms; D005947:Glucose