Dipeptidyl Peptidase‐4 Inhibitors Attenuate Endothelial Function as Evaluated by Flow‐Mediated Vasodilatation in Type 2 Diabetic Patients

Autor: Makoto Ayaori, Naotsugu Iwakami, Emi Yakushiji, Bonpei Takase, Maki Iizuka, Makoto Sasaki, Shunichi Takiguchi, Tomohiro Komatsu, Hiroki Sato, Harumi Uto-Kondo, Masatsune Ogura, Kazuhiro Nakaya, Makiko Yogo, Katsunori Ikewaki, Takehiko Murakami
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Blood Glucose
Male
Time Factors
Type 2 diabetes
Pharmacology
Vascular Medicine
endothelial function
Japan
Piperidines
Prospective Studies
Endothelial dysfunction
Original Research
Cross-Over Studies
Middle Aged
Vasodilation
Treatment Outcome
Sitagliptin
Pyrazines
Female
type 2 diabetes
Cardiology and Cardiovascular Medicine
Alogliptin
medicine.drug
Adult
medicine.medical_specialty
flow‐mediated vasodilatation
Sitagliptin Phosphate
Internal medicine
Voglibose
medicine
Humans
Uracil
Dipeptidyl peptidase-4
Aged
DPP‐4 inhibitors
Dipeptidyl-Peptidase IV Inhibitors
business.industry
Cholesterol
LDL
Triazoles
medicine.disease
Crossover study
Endocrinology
Diabetes Mellitus
Type 2
Regional Blood Flow
Linear Models
Endothelium
Vascular
Hydroxymethylglutaryl-CoA Reductase Inhibitors
business
Biomarkers
Inositol
Zdroj: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
ISSN: 2047-9980
Popis: Background Endothelial dysfunction is an independent predictor for cardiovascular events in patients with type 2 diabetes ( T2DM ). Glucagon like peptide‐1 ( GLP ‐1) reportedly exerts vasodilatory actions, and inhibitors of dipeptidyl peptidase‐4 ( DPP ‐4), an enzyme‐degrading GLP ‐1, are widely used to treat T2DM . We therefore hypothesized that DPP ‐4 inhibitors ( DPP ‐4Is) improve endothelial function in T2DM patients and performed 2 prospective, randomized crossover trials to compare the DPP ‐4I sitagliptin and an α‐glucosidase inhibitor, voglibose (in study 1) and the DPP ‐4Is sitagliptin and alogliptin (in study 2). Methods and Results In study 1, 24 men with T2DM (46±5 years) were randomized to sitagliptin or voglibose for 6 weeks without washout periods. Surprisingly, sitagliptin significantly reduced flow‐mediated vasodilatation ( FMD ; −51% compared with baseline, P FMD . To confirm this result and determine whether it is a class effect, we conducted another trial (study 2) to compare sitagliptin and alogliptin in 42 T2DM patients (66±8 years) for 6 weeks with 4‐week washout periods. Both DPP ‐4Is improved glycemic control but significantly attenuated FMD (7.2/4.3%, P P FMD reduction was less evident in subjects who were on statins or whose LDL cholesterol levels were reduced by them, but this was not correlated with parameters including DPP ‐4 activity and GLP ‐1 levels or diabetic parameters. Conclusions Our 2 independent trials demonstrated that DPP ‐4 inhibition attenuated endothelial function as evaluated by FMD in T2DM patients. This unexpected unfavorable effect may be a class effect of DPP ‐4Is. Clinical Trial Registration URL: http://center.umin.ac.jp , Unique Identifiers: UMIN000005682 (sitagliptin versus voglibose) and UMIN000005681 (sitagliptin versus alogliptin).
Databáze: OpenAIRE
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