J Korean Med Sci.  2012 Nov;27(11):1364-1370. 10.3346/jkms.2012.27.11.1364.

The Dipeptidyl Peptidase-4 Inhibitor Sitagliptin Improves Vascular Endothelial Function in Type 2 Diabetes

• Kubota Y
• Miyamoto M
• Takagi G
• Ikeda T
• Kirinoki-Ichikawa S
• Tanaka K
• Mizuno K

• KMID: 2157948
• DOI: http://doi.org/10.3346/jkms.2012.27.11.1364

Abstract

The vascular endothelial function is impaired in the very early stage of atherosclerosis in diabetic patients. The goal of this study was to identify the mechanism underlying the improvement in vascular endothelial function by sitagliptin in type 2 diabetes mellitus patients. This study was an open-labeled prospective observational single arm trial. Forty patients were treated with 50 mg of sitagliptin once daily for 12-weeks. The flow-mediated dilation (FMD) and plasma adiponectin were measured at baseline and 12 weeks after initiating treatment. The %FMD was significantly increased after treatment (4.13 +/- 1.59 vs 5.12 +/- 1.55, P < 0.001), whereas the nitroglycerin-mediated dilation (NMD) did not change. The plasma adiponectin levels significantly increased (13.0 +/- 11.3 vs 14.3 +/- 12.8, P < 0.001). The changes in the FMD were significantly correlated with those of the plasma adiponectin (r = 0.322, P < 0.05). A multivariate linear regression analysis demonstrated that the improvement in the FMD is associated with the plasma adiponectin (P < 0.05). The treatment of type 2 diabetes mellitus patients with sitagliptin reverses vascular endothelial dysfunction, as evidenced by increase in the FMD, and improvement of the adiponectin levels (UMIN Clinical Trials Registry System as trial ID UMIN000004236).

Keyword

Endothelial Function; Dipeptidyl Peptidase-4 Inhibitor; Adiponectin; Type 2 Diabetes Mellitus

MeSH Terms

Adiponectin/blood
Aged
Aged, 80 and over
Atherosclerosis/complications/drug therapy
Diabetes Mellitus, Type 2/complications/*drug therapy
Dipeptidyl-Peptidase IV Inhibitors/pharmacology/*therapeutic use
Drug Administration Schedule
Endothelium, Vascular/*drug effects/physiopathology
Female
Humans
Male
Middle Aged
Nitroglycerin/therapeutic use
Prospective Studies
Pyrazines/pharmacology/*therapeutic use
Regression Analysis
Triazoles/pharmacology/*therapeutic use
Vasodilation/drug effects
Vasodilator Agents/therapeutic use
Adiponectin
Dipeptidyl-Peptidase IV Inhibitors
Pyrazines
Triazoles
Vasodilator Agents
Nitroglycerin

Figure

• 

  Fig. 1 Changes of the %FMD, %NMD and FMD/NMD ratio before and after treatment with sitagliptin therapy. (A) Flow mediated dilation (FMD) is significantly improved after 12 weeks. (B) Nitroglycerin-mediated dilation (NMD) is not improved. (C) An improved FMD/NMD ratio implies recovery of specific endothelial dysfunction. Columns are means ± SD. *P < 0.001 vs baseline.

• 

  Fig. 2 Univariate correlations between the changes of %FMD (ΔFMD) and those of Δadiponectin, ΔADMA, and ΔHbA1c between baseline and after 12 weeks with sitagliptin therapy in type 2 diabetes.

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