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


BACKGROUND
This study is registered on http://www.clinicaltrials.gov/: NCT00546728.
Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN, USA. kelly105@umn.edu
Aaron S
AS
Kelly
Richard M
RM
Bergenstal
J Michael
JM
Gonzalez-Campoy
Harold
H
Katz
Alan J
AJ
Bank
D000368:Aged; D000704:Analysis of Variance; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D000077270:Exenatide; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D006940:Hyperemia / Q000503:physiopathology; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D018836:Inflammation Mediators / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008833:Microcirculation / Q000187:drug effects*; D008875:Middle Aged; D056128:Obesity, Abdominal / Q000097:blood / Q000150:complications* / Q000503:physiopathology; D010455:Peptides / Q000627:therapeutic use*; D011236:Prediabetic State / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D013997:Time Factors; D016896:Treatment Outcome; D034941:Upper Extremity / Q000098:blood supply*; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood; D014688:Venoms / Q000627:therapeutic use*
D015415:Biomarkers; D001786:Blood Glucose; D002097:C-Reactive Protein; D000077270:Exenatide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D018836:Inflammation Mediators; D008077:Lipoproteins, LDL; D008687:Metformin; D010455:Peptides; D019010:Vascular Cell Adhesion Molecule-1; D014688:Venoms; C517652:hemoglobin A1c protein, human; C099252:oxidized low density lipoprotein