title: Treatment with exenatide once weekly or twice daily for 30 weeks is associated with changes in several cardiovascular risk markers.
abstract: BACKGROUND
  Cyslipidemia and type 2 diabetes are two of the most significant risk factors for the development of cardiovascular disease. Measurement of lipoprotein subclasses provides important information about derangements in lipid metabolism and helps refine cardiovascular risk assessment. Exenatide, a glucagon-like peptide 1 receptor agonist, improved glycemic control, obesity, hypertension, and dyslipidemia in patients with type 2 diabetes in clinical trials.
  
  
  METHODS
  In the DURATION-1 trial, patients with type 2 diabetes were treated with exenatide once weekly or twice daily for 30 weeks. This post hoc analysis evaluated the impact of exenatide on lipoprotein subclasses in 211 DURATION-1 patients using vertical auto profile methodology and the Statistical Package for the Social Sciences general linear model adjusted for glycosylated hemoglobin (HbA(1c)) and weight.
  
  
  RESULTS
  Baseline lipids and high sensitivity C-reactive protein were normal overall based on the standard lipid panel. Once-weekly exenatide reduced apolipoprotein B and the apolipoprotein B to apolipoprotein A1 ratio (P < 0.05), independent of glycemic improvement and weight loss. A significant shift in lipoprotein pattern away from small, dense low-density lipoprotein-4 cholesterol was also observed (P < 0.05). Exenatide once weekly increased high-density lipoprotein-2 cholesterol, even after adjustment for changes in HbA(1c) and weight (P < 0.05). Triglycerides, very low-density lipoprotein cholesterol, and high sensitivity C-reactive protein were reduced with both the once-weekly and twice-daily exenatide regimens (P < 0.05).
  
  
  CONCLUSIONS
  In this post hoc analysis, exenatide significantly improved a number of cardiovascular risk markers. Continuous exenatide exposure with exenatide once weekly elicited a greater response than did immediate-release exenatide twice daily, generally independent of glycemic improvement and weight loss. Thus, in addition to improving glycemic control, exenatide induced favorable changes in lipid and lipoprotein metabolism and decreased systemic inflammation.
authors.affiliation: Amylin Pharmaceuticals, San Diego, CA, USA. elaine.chiquette@amylin.com
authors.forename: Elaine
authors.initials: E
authors.lastname: Chiquette
authors.forename: Peter P
authors.initials: PP
authors.lastname: Toth
authors.forename: Gilbert
authors.initials: G
authors.lastname: Ramirez
authors.forename: Michael
authors.initials: M
authors.lastname: Cobble
authors.forename: Robert
authors.initials: R
authors.lastname: Chilton
mesh_terms: D001053:Apolipoproteins / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001835:Body Weight / Q000187:drug effects; D002097:C-Reactive Protein / Q000032:analysis; D002318:Cardiovascular Diseases / Q000517:prevention & control*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D000077270:Exenatide; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000008:administration & dosage / Q000627:therapeutic use*; D012307:Risk Factors; D014688:Venoms / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D001053:Apolipoproteins; D015415:Biomarkers; D002097:C-Reactive Protein; D000077270:Exenatide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008074:Lipoproteins; D010455:Peptides; D014688:Venoms