Effects of exenatide vs. metformin on endothelial function in obese patients with pre-diabetes: a randomized trial

Aaron S Kelly, Richard M Bergenstal, J Michael Gonzalez-Campoy, Harold Katz, Alan J Bank, Aaron S Kelly, Richard M Bergenstal, J Michael Gonzalez-Campoy, Harold Katz, Alan J Bank

Abstract

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 (Δ exenatide: 0.01 ± 0.68 vs. Δ 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 (Δ exenatide: -25.5 ± 45.7 mg/dL vs. Δ 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.

Clinical trials registration: This study is registered on http://www.clinicaltrials.gov/: NCT00546728.

Figures

Figure 1
Figure 1
Endothelial function before and after 3-months of treatment with either exenatide or metformin.
Figure 2
Figure 2
Serial endothelial function during the OGTT for control (no drug pre-administration) and pre-administration of either exenatide or metformin.

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