Long-term effect of sitagliptin on endothelial function in type 2 diabetes: a sub-analysis of the PROLOGUE study.
As a sub-analysis of the PROLOGUE study, we evaluated the long-term effect of sitagliptin, a dipeptidyl peptidase 4 inhibitor, on endothelial function in the conduit brachial artery in patients with type 2 diabetes.



In the PROLOGUE study, patients were randomly assigned to either add-on sitagliptin treatment (sitagliptin group) or continued conventional antihyperglycemic treatment (conventional group). Among the 463 participants in the PROLOGUE study, FMD was measured in 17 patients in the sitagliptin group and 18 patients in the conventional group at the beginning and after 12 and 24 months of treatment.



HbA1c levels were significantly decreased after 12 and 24 months of treatment compared to baseline values in both groups (7.0 ± 0.4 vs. 6.6 ± 0.3 and 6.6 ± 0.4 % in the sitagliptin group; 7.0 ± 0.6 vs. 6.6 ± 0.7 and 6.6 ± 0.7 % in the conventional group; P < 0.05, respectively). There was no significant difference between FMD values at baseline and after 12 and 24 months in the sitagliptin group (4.3 ± 2.6 vs. 4.4 ± 2.1 and 4.4 ± 2.3 %, P = 1.0, respectively). Although FMD had a tendency to increase from 4.3 ± 2.4 % at baseline to 5.2 ± 1.9 % after 12 months and 5.1 ± 2.2 % after 24 months in the conventional group, there was no significant difference between FMD values at baseline and after 12 and 24 months (P = 0.36 and 0.33, respectively).



Add-on sitagliptin to conventional antihyperglycemic drugs in patients with type 2 diabetes did not alter endothelial function in the conduit brachial artery measured by FMD during a 2-year study period. Sitagliptin may be used without concern for an adverse effect on endothelial function in patients with type 2 diabetes.



University hospital Medical Information Network (UMIN) Center: ID UMIN000004490.
Department of Cardiovascular Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
Tatsuya
T
Maruhashi
Division of Regeneration and Medicine, Medical Center for Translational and Clinical Research, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan. yhigashi@hiroshima-u.ac.jp.|Department of Cardiovascular Regeneration and Medicine, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan. yhigashi@hiroshima-u.ac.jp.
Yukihito
Y
Higashi
Department of Cardiovascular Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
Yasuki
Y
Kihara
Department of Cardiovascular Medicine, Tokushima University Hospital, 2-50-1 Kuramoto-cho, Tokushima, 770-0042, Japan.
Hirotsugu
H
Yamada
Department of Cardiovascular Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-0042, Japan.
Masataka
M
Sata
Department of Clinical Pharmacology and Therapeutics, University of the Ryukyus, 207 Uehara, Nishihara-cho, Okinawa, 903-0215, Japan.
Shinichiro
S
Ueda
Department of Diabetes, Endocrinology, Metabolism and Rheumatology, Tokyo Medical University, 6-1-1 Nishishinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan.
Masato
M
Odawara
Department of Endocrinology and Metabolism, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
Yasuo
Y
Terauchi
Department of Cardiology, Hiroshima City Hospital, 7-33 Motomachi, Naka-ku, Hiroshima, 730-0011, Japan.
Kazuoki
K
Dai
Department of Cardiology, Tsushima Municipal Hospital, 3-73 Tachibana-cho, Tsushima, 496-0038, Japan.
Jun
J
Ohno
Department of Cardiology, Mitsubishi Nagoya Hospital, 7-8 Sotodoi-cho, Atsuta-ku, Nagoya, 456-0013, Japan.
Masato
M
Iida
Department of Cardiology, Nagoya Ekisaikai Hospital, 4-66, Syounen-cho, Nakagawa-ku, Nagoya, 454-0854, Japan.
Hiroaki
H
Sano
Department of Cardiology, Tokyo Medical University, 6-7-1, Nishishinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan.
Hirofumi
H
Tomiyama
Department of Cardiovascular Medicine, Dokkyo Medical University, 880 Kitakobayashi, Mibumachi, Shimotsuga-gun, Tochigi, 321-0293, Japan.
Teruo
T
Inoue
Department of Cardiovascular Medicine, Saga University, 5-1-1, Nabeshima, Saga, 849-0937, Japan.
Atsushi
A
Tanaka
Department of Cardiology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Shouwa-ku, Nagoya, 466-0065, Japan.
Toyoaki
T
Murohara
Department of Cardiovascular Medicine, Saga University, 5-1-1, Nabeshima, Saga, 849-0937, Japan.
Koichi
K
Node
D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001916:Brachial Artery / Q000187:drug effects* / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D000068900:Sitagliptin Phosphate / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D014664:Vasodilation / Q000187:drug effects*
D015415:Biomarkers; D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D006442:Glycated Hemoglobin; D000068900:Sitagliptin Phosphate; C517652:hemoglobin A1c protein, human
Dipeptidyl peptidase 4 inhibitor; Flow-mediated vasodilation; Type 2 diabetes