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

Aaron S Kelly1*, Richard M Bergenstal2, J Michael Gonzalez-Campoy3, Harold Katz4 and Alan J Bank5

Author Affiliations

1 Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN, USA

2 International Diabetes Center at Park Nicollet, St. Louis Park, MN, USA

3 Minnesota Center for Obesity, Metabolism and Endocrinology, Eagan, MN, USA

4 Allina Hospitals and Clinics, St. Paul, MN, USA

5 United Heart and Vascular Clinic, St. Paul, MN, USA

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Cardiovascular Diabetology 2012, 11:64  doi:10.1186/1475-2840-11-64

Published: 8 June 2012



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.


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.


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.


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 NCT00546728 webcite

Exenatide; Metformin; Endothelial function; Obesity; Pre-diabetes