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Impact of DPP-4 inhibition on acute and chronic endothelial function in humans with type 2 diabetes on background metformin therapy. Vasc Med 2017 06;22(3):189-196

Date

02/02/2017

Pubmed ID

28145158

Pubmed Central ID

PMC5609820

DOI

10.1177/1358863X16681486

Scopus ID

2-s2.0-85019239505   14 Citations

Abstract

: Cell culture and animal work indicate that dipeptidyl peptidase-4 (DPP-4) inhibition may exert cardiovascular benefits through favorable effects on the vascular endothelium. Prior human studies evaluating DPP-4 inhibition have shown conflicting results that may in part be related to heterogeneity of background anti-diabetes therapies. No study has evaluated the acute response of the vasculature to DPP-4 inhibition in humans. We recruited 38 patients with type 2 diabetes on stable background metformin therapy for a randomized, double-blind, placebo-controlled crossover trial of DPP-4 inhibition with sitagliptin (100 mg/day). Each treatment period was 8 weeks long separated by 4 weeks of washout. Endothelial function and plasma markers of endothelial activation (intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1)) were measured prior to and 2 hours following acute dosing of sitagliptin or placebo, as well as following 8 weeks of intervention with each pill. Thirty subjects completed the study and were included in analyses. Neither acute nor chronic sitagliptin therapy resulted in significant changes in vascular endothelial function. While post-acute sitagliptin ICAM-1 levels were lower than that post-chronic sitagliptin, the ICAM-1 concentration was not significantly different than pre-acute sitagliptin levels or levels measured in relationship to placebo. There were no significant changes in plasma VCAM-1 levels at any time point. Acute and chronic sitagliptin therapies have neutral effects on the vascular endothelium in the setting of metformin background therapy. In conclusion, our findings suggest DPP-4 inhibition has a neutral effect on cardiovascular risk in patients without a history of heart failure or renal insufficiency.

TRIAL REGISTRATION: NCT01859793.

Author List

Widlansky ME, Puppala VK, Suboc TM, Malik M, Branum A, Signorelli K, Wang J, Ying R, Tanner MJ, Tyagi S

Author

Michael E. Widlansky MD Associate Director, Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adult
Aged
Biomarkers
Cross-Over Studies
Diabetes Mellitus, Type 2
Dipeptidyl Peptidase 4
Dipeptidyl-Peptidase IV Inhibitors
Double-Blind Method
Drug Therapy, Combination
Endothelium, Vascular
Female
Humans
Intercellular Adhesion Molecule-1
Male
Metformin
Middle Aged
Sitagliptin Phosphate
Time Factors
Treatment Outcome
Vascular Cell Adhesion Molecule-1
Vasodilation
Wisconsin
Young Adult
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