Diabetes: assessing the pipeline.
Type 2 diabetes is recognised as a major cardiovascular risk factor, and future therapies must therefore address more than just blood glucose levels. Novel approaches to the treatment of type 2 diabetes are now at various stages of development or regulatory approval. Exenatide and pramlintide, analogues of gut-derived hormones glucagon-like peptide-1 (GLP-1) and amylin, respectively, have demonstrated improvements in glycaemic control and bodyweight in clinical studies and have been recently approved for treatment of type 2 diabetes. Initial studies have indicated that agents that activate both peroxisome proliferator-activated receptor (PPAR)alpha and gamma improve glycaemic control and have beneficial effects on lipid profiles. Two dual PPARalpha/gamma agonists, muraglitazar and tesaglitazar, are under regulatory review and in phase III trials, respectively. Modulation of the endogenous endocannabinoid system by rimonabant, which is under regulatory review, has been shown to improve body weight, atherogenic lipid profiles and glycaemic control. In addition, enhanced understanding of the pathophysiology underlying the microvascular complications of type 2 diabetes has led to the development of targeted therapies for conditions such as diabetic retinopathy, including the protein kinase C (PKC)-antagonist ruboxistaurin, now in phase III trials. Such therapies should enable physicians to achieve more for their patients with type 2 diabetes.
Lebovitz
Harold
H
Department of Medicine, State University of New York Health Science Center at Brooklyn, Staten Island, NY 10310-1617, USA. hlebovitz@attglobal.net
D000218:Adamantane / Q000031:analogs & derivatives / Q000627:therapeutic use; D000476:Alkanesulfonates / Q000627:therapeutic use; D000682:Amyloid / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D000077270:Exenatide; D005998:Glycine / Q000031:analogs & derivatives / Q000627:therapeutic use; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007211:Indoles / Q000627:therapeutic use; D058228:Islet Amyloid Polypeptide; D008301:Maleimides / Q000627:therapeutic use; D009570:Nitriles; D010080:Oxazoles / Q000627:therapeutic use; D047493:PPAR alpha / Q000819:agonists; D047495:PPAR gamma / Q000819:agonists; D010455:Peptides / Q000627:therapeutic use; D010666:Phenylpropionates / Q000627:therapeutic use; D010880:Piperidines / Q000627:therapeutic use; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011720:Pyrazoles / Q000627:therapeutic use; D011759:Pyrrolidines; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors; D018027:Receptors, Glucagon / Q000819:agonists; D000077285:Rimonabant; D014688:Venoms / Q000627:therapeutic use; D000077597:Vildagliptin
D000476:Alkanesulfonates; D000682:Amyloid; D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D007211:Indoles; D058228:Islet Amyloid Polypeptide; D008301:Maleimides; D009570:Nitriles; D010080:Oxazoles; D047493:PPAR alpha; D047495:PPAR gamma; D010455:Peptides; D010666:Phenylpropionates; D010880:Piperidines; D011720:Pyrazoles; D011759:Pyrrolidines; D043884:Receptor, Cannabinoid, CB1; D018027:Receptors, Glucagon; D014688:Venoms; C501413:tesaglitazar; C099154:ruboxistaurin; D000077270:Exenatide; C105254:pramlintide; D011493:Protein Kinase C; D000077597:Vildagliptin; D000218:Adamantane; D000077285:Rimonabant; D005998:Glycine; C500085:muraglitazar