title: Effects of sitagliptin on coronary atherosclerosis in patients with type 2 diabetes-A serial integrated backscatter-intravascular ultrasound study.
abstract: Dipeptidyl peptidase-4 (DPP-4) inhibitors have demonstrated anti-inflammatory and anti-atherogenic effects in an animal model. However, the clinical usefulness of DPP-4 inhibitors, particularly its effects on coronary atherosclerosis, has not been evaluated thus far. Therefore, in this study, we evaluated the effects of sitagliptin, a DPP-4 inhibitor, on coronary atherosclerosis using integrated backscatter (IB)-intravascular ultrasound (IVUS) in patients with type 2 diabetes. This trial was a prospective, open-labeled, randomized, multicenter study. Twenty-eight patients with type 2 diabetes who underwent elective percutaneous coronary intervention (PCI) were randomly assigned to either the sitagliptin group (group S) or the control group (group C). Non-PCI lesions were evaluated using IB-IVUS at the time of PCI and at the 48-week follow-up. The primary endpoint was the percentage change in plaque volume measured using grayscale IVUS, and the secondary endpoint was changes in plaque composition evaluated using IB-IVUS. Grayscale IVUS analysis demonstrated that plaque volume tended to decrease in both groups (group S: -1.7±8.5%; group C: -3.2±12.2%), but a between-group difference was not observed. A decrease in the lipid plaque volume (group S: from 200.1±116.2 to 179.8±121.0 mm3, P = 0.02; group C: from 298.3±363.0 to 256.6±386.1 mm3, P = 0.1) and an increase in the calcified plaque volume (group S: from 2.1±0.9 to 3.2±1.8 mm3, P = 0.06; group C: from 2.3±1.7 to 4.8±3.5 mm3, P = 0.04) was observed on IB-IVUS analysis. Univariate and multivariate regression analyses showed that the percentage change in serum non-high-density lipoprotein (HDL) cholesterol level was an independent and significant predictor of a reduction in lipid plaque volume (β = 0.445, P = 0.04). In conclusions, sitagliptin did not significantly reduce coronary plaque volume in patients with type 2 diabetes. However, a decrease in the lipid plaque volume was observed in the sitagliptin group. A decrease in non-HDL cholesterol level was associated with a reduction in the lipid volume of coronary artery plaques.
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Yokohama Sakae Kyosai Hospital Yokohama, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Nozue
authors.affiliation: Department of Cardiology, Kanagawa Cardiovascular and Respiratory Center Yokohama, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Fukui
authors.affiliation: Cardiovascular Center, Tokyo Kamata Hospital Tokyo, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Koyama
authors.affiliation: Department of Cardiology, Yokohama Minami Kyosai Hospital Yokohama, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Fujii
authors.affiliation: Fourth Department of Internal Medicine, Mizonokuchi Hospital, School of Medicine, Teikyo University Kawasaki, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Kunishima
authors.affiliation: Cardiovascular Center, Yokosuka Kyosai Hospital Yokosuka, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hikita
authors.affiliation: Division of Cardiology, Yokohama City University Medical Center Yokohama, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Hibi
authors.affiliation: Cardiocore Japan Tokyo, Japan.
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Miyazawa
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Yokohama Sakae Kyosai Hospital Yokohama, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Michishita
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Yokohama Sakae Kyosai Hospital Yokohama, Japan.
keywords: Coronary atherosclerosis; diabetes mellitus; dipeptidyl peptidase-4 inhibitor; intravascular ultrasound; sitagliptin