Treatment with exenatide once weekly or twice daily for 30 weeks is associated with changes in several cardiovascular risk markers

Elaine Chiquette, Peter P. Toth, Gilbert Ramirez, Michael Cobble, Robert J Chilton

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Background: Dyslipidemia 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 (HbA1c) 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 HbA1c 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). Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)621-629
Number of pages9
JournalVascular Health and Risk Management
Volume8
Issue number1
DOIs
StatePublished - 2012

Fingerprint

Lipoproteins
Therapeutics
Type 2 Diabetes Mellitus
Apolipoproteins B
Dyslipidemias
Lipid Metabolism
C-Reactive Protein
Weight Loss
exenatide
HDL2 Lipoprotein
Lipids
Weights and Measures
VLDL Cholesterol
Social Sciences
Apolipoprotein A-I
Glycosylated Hemoglobin A
LDL Cholesterol
HDL Cholesterol
Linear Models
Triglycerides

Keywords

  • Dyslipidemia
  • Glucagon-like protein-1 receptor agonist
  • Incretin mimetic
  • Type 2 diabetes mellitus

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Pharmacology (medical)
  • Public Health, Environmental and Occupational Health
  • Hematology
  • Endocrinology, Diabetes and Metabolism

Cite this

Treatment with exenatide once weekly or twice daily for 30 weeks is associated with changes in several cardiovascular risk markers. / Chiquette, Elaine; Toth, Peter P.; Ramirez, Gilbert; Cobble, Michael; Chilton, Robert J.

In: Vascular Health and Risk Management, Vol. 8, No. 1, 2012, p. 621-629.

Research output: Contribution to journalArticle

Chiquette, Elaine ; Toth, Peter P. ; Ramirez, Gilbert ; Cobble, Michael ; Chilton, Robert J. / Treatment with exenatide once weekly or twice daily for 30 weeks is associated with changes in several cardiovascular risk markers. In: Vascular Health and Risk Management. 2012 ; Vol. 8, No. 1. pp. 621-629.
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T1 - Treatment with exenatide once weekly or twice daily for 30 weeks is associated with changes in several cardiovascular risk markers

AU - Chiquette, Elaine

AU - Toth, Peter P.

AU - Ramirez, Gilbert

AU - Cobble, Michael

AU - Chilton, Robert J

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AB - Background: Dyslipidemia 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 (HbA1c) 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 HbA1c 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). Conclusion: 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.

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KW - Incretin mimetic

KW - Type 2 diabetes mellitus

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