Journal
CARDIOVASCULAR DIABETOLOGY
Volume 11, Issue -, Pages -Publisher
BMC
DOI: 10.1186/1475-2840-11-64
Keywords
Exenatide; Metformin; Endothelial function; Obesity; Pre-diabetes
Funding
- GlaxoSmithKline
- Amylin/Eli Lilly
- Amylin
- Eli Lilly
- Novo Nordisk
- Sanofi
- Boehringer Ingelheim
- Merck
- Roche
- Takeda
- Pfizer
- Sanofi-Aventis
- Leptos
- Astra-Zeneca
- Ipsen
- Amylin Pharmaceuticals
- Eli Lilly and Company
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Background: Glucagon like peptide-1 (GLP-1) receptor agonist treatment may improve endothelial function via direct and indirect mechanisms. We compared the acute and chronic effects of the GLP-1 receptor agonist exenatide vs. metformin on endothelial function in patients with obesity and pre-diabetes. Methods: We performed a randomized, open-label, clinical trial in 50 non-diabetic individuals (mean age 58.5 +/- 10.0; 38 females) with abdominal obesity and either impaired fasting glucose, elevated HbA1c, or impaired glucose tolerance (IGT) who were randomized to receive 3-months of exenatide or metformin. Microvascular endothelial function, assessed by digital reactive hyperemia (reactive hyperemic index: RHI), C-reactive protein (CRP), circulating oxidized LDL (oxLDL), and vascular cell adhesion molecule-1 (VCAM-1) were measured at baseline and 3-months. Seven subjects with IGT participated in a sub-study comparing the effects of pre-administration of exenatide and metformin on postprandial endothelial function. Results: There were no differences for the change in RHI (Delta exenatide: 0.01 +/- 0.68 vs. Delta metformin: -0.17 +/- 0.72, P = 0.348), CRP, oxLDL, or VCAM-1 between exenatide and metformin treatment. Triglycerides were reduced more with exenatide compared to metformin (Delta exenatide: -25.5 +/- 45.7 mg/dL vs. Delta metformin: -2.9 +/- 22.8 mg/dL, P = 0.032). In the sub-study, there was no difference in postprandial RHI between exenatide and metformin. Conclusions: Three months of exenatide therapy had similar effects on microvascular endothelial function, markers of inflammation, oxidative stress, and vascular activation, as metformin, in patients with obesity and pre-diabetes.
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