Amylin agonists: a novel approach in the treatment of diabetes.
Amylin is a peptide hormone that is cosecreted with insulin from the pancreatic beta-cell and is thus deficient in diabetic people. It inhibits glucagon secretion, delays gastric emptying, and acts as a satiety agent. Amylin replacement could therefore possibly improve glycemic control in some people with diabetes. However, human amylin exhibits physicochemical properties predisposing the peptide hormone to aggregate and form amyloid fibers, which may play a part in beta-cell destruction in type 2 diabetes. This obviously makes it unsuitable for pharmacological use. A stable analog, pramlintide, which has actions and pharmacokinetic and pharmacodynamic properties similar to the native peptide, has been developed. The efficacy and safety of pramlintide administration has been tested in a vast number of clinical trials. Approximately 5,000 insulin-treated patients have received pramlintide and approximately 250 for > or =2 years. The aims of this review are to 1) briefly describe actions of amylin as demonstrated in animal and human models and 2) primarily review results from clinical trials with the amylin analog pramlintide.
Schmitz
Ole
O
Department of Clinical Pharmacology, The Bartholin Building, University of Aarhus, DK 8000 Aarhus C, Denmark. ole.schmitz@iekf.au.dk
Brock
Birgitte
B
Rungby
Jorgen
J
D000682:Amyloid / Q000819:agonists* / Q000502:physiology / Q000627:therapeutic use; D000818:Animals; D002986:Clinical Trials as Topic; D003920:Diabetes Mellitus / Q000188:drug therapy*; D004195:Disease Models, Animal; D006442:Glycated Hemoglobin / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000627:therapeutic use; D058228:Islet Amyloid Polypeptide
D000682:Amyloid; D006442:Glycated Hemoglobin; D007328:Insulin; D058228:Islet Amyloid Polypeptide; C105254:pramlintide