Impact of glycemic control with sitagliptin on the 2-year progression of arterial stiffness: a sub-analysis of the PROLOGUE study.
No conclusive evidence has been obtained yet on the significance of the effects of dipeptidyl peptidase-4 (DPP-4 inhibitor) treatment on the arterial stiffness in clinical settings. In addition, the effects of good glycemic control on the arterial stiffness have also not been clarified yet. As a sub-analysis of the PROLOGUE study, we examined the effect of a DPP-4 inhibitor (sitagliptin) on the 2-year progression of the arterial stiffness and also to determine the effect of good glycemic control on the rate of progression of the arterial stiffness.



In the PROLOGUE study, the study participants were either allocated to add-on sitagliptin treatment or to continued treatment with conventional anti-diabetic agents. Among the 463 participants of the PROLOGUE study, we succeeded in measuring the brachial-ankle pulse wave velocity (baPWV) at least two times during the 2-year study period in 96 subjects.



The changes in the baPWV during the study period were similar between the both groups (i.e., with/without staglipitin), overall. On the other hand, when the study subjects were divided into two groups according to the glycemic control status during the study period {good glycemic control group (GC) = hemoglobin (Hb)A1c <7.0 at both 12 and 24 months after the treatment randomization; poor glycemic control group (PC) = HbA1c ≥7.0 at either 12 months, 24 months, or both}, the 2-year increase of the baPWV was marginally significantly larger in the PC group (144 ± 235 cm/s) as compared to that the GC group (-10 ± 282 cm/s) (p = 0.036).



While the present study could not confirm the beneficial effect of sitagliptin per se on the arterial stiffness, the results suggested that good glycemic control appears to be beneficial for delaying the annual progression of the arterial stiffness. Trial registration University Hospital Medical Information Network Clinical Trials Registry UMIN000004490.
Department of Cardiology, Tokyo Medical University, 6-7-1 Nishi-Shinjuku, Tokyo, Japan. tomiyama@tokyo-med.ac.jp.
Hirofumi
H
Tomiyama
Department of Diabetes, Endocrinology, Metabolism and Rheumatology, Tokyo Medical University, Tokyo, Japan.
Takashi
T
Miwa
Division of Diabetes, Metabolism and Endocrinology, Tokyo Medical University Hospital, Tokyo, Japan.
Kenshi
K
Kan
Diabetes Therapeutics and Research Center, Tokushima University, Tokushima, Japan.
Munehide
M
Matsuhisa
Division of Cardiology, Japanese Red Cross Nagoya Daiichi Hospital, Nagoya, Japan.
Haruo
H
Kamiya
Cardiovascular Center, Japanese Red Cross Nagoya Daini Hospital, Nagoya, Japan.
Mamoru
M
Nanasato
Department of Cardiology, National Hospital Organization Nagoya Medical Center, Nagoya, Japan.
Tomoki
T
Kitano
Department of Cardiology, Nagoya Ekisaikai Hospital, Nagoya, Japan.
Hiroaki
H
Sano
Department of Cardiology, Tsushima Municipal Hospital, Tsushima, Japan.
Jun
J
Ohno
Department of Cardiology, Mitsubishi Nagoya Hospital, Nagoya, Japan.
Masato
M
Iida
Department of Cardiovascular Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
Masataka
M
Sata
Department of Cardiovascular Medicine, Tokushima University Hospital, Tokushima, Japan.
Hirotsugu
H
Yamada
Department of Cardiovascular Medicine, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
Koji
K
Maemura
Department of Cardiovascular Medicine, Saga University, Saga, Japan.
Atsushi
A
Tanaka
Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Toyoaki
T
Murohara
Department of Cardiovascular Medicine, Saga University, Saga, Japan.
Koichi
K
Node
D000368:Aged; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000201:enzymology; D003925:Diabetic Angiopathies / Q000175:diagnosis / Q000503:physiopathology / Q000517:prevention & control*; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D018450:Disease Progression; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D063177:Pulse Wave Analysis; D000068900:Sitagliptin Phosphate / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D059289:Vascular Stiffness / Q000187:drug effects*
D015415:Biomarkers; D001786:Blood Glucose; D018819:Dipeptidyl Peptidase 4; D054873:Dipeptidyl-Peptidase IV Inhibitors; D006442:Glycated Hemoglobin; D000068900:Sitagliptin Phosphate; C517652:hemoglobin A1c protein, human; C042807:DPP4 protein, human
Arterial stiffness; Dipeptidyl peptidase 4 inhibitor; Glycemic control