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Anagliptin, A Dipeptidyl Peptidase-4 Inhibitor Ameliorates Arterial Stiffness in Association with Reduction of Remnant-Like Particle Cholesterol and Alanine Transaminase Levels in Type 2 Diabetic Patients

[ Vol. 14 , Issue. 6 ]

Author(s):

Nobuhiro Tahara, Sho-ichi Yamagishi, Munehisa Bekki, Norihiro Kodama, Tomohisa Nakamura, Yoichi Sugiyama, Tamami Oshige, Yuki Kumashiro, Akihiro Honda, Atsuko Tahara, Sachiyo Igata and Yoshihiro Fukumoto   Pages 552 - 562 ( 11 )

Abstract:


Background: Inhibition of dipeptidyl peptidase-4 (DPP-4) has been proposed as a therapeutic target for type 2 diabetes (T2DM). Arterial stiffness, a predictor of future cardiovascular events and all-cause mortality, is augmented in these patients. However, effects of DPP-4 inhibitors on arterial stiffness remain unknown. In this study, we compared effects of anagliptin, an inhibitor of DPP-4 on arterial stiffness evaluated by cardio-ankle vascular index (CAVI) with those of an equipotent glucose-lowering agent, glimepiride in patients with T2DM.

Methods: The study involved 50 consecutive outpatients (33 males and 17 females; mean age of 72.5±9.5 years) who visited our hospitals for a risk-screening test or treatment for T2DM. They underwent complete history and physical examination, and determination of blood chemistry and anthropometric variables, and then were randomized to receive either anagliptin (n=26) or glimepiride (n=24) for 6 months.

Results: After 6-months treatment, fasting plasma glucose and HbA1c values were comparably reduced in both groups. Anagliptin, but not glimepiride treatment significantly decreased low-density lipoprotein cholesterol, malondialdehyde-modified LDL, remnant-like particle (RLP) cholesterol, CAVI, alanine transaminase (ALT), γ-glutamyl transferase and visceral fat volume. In multiple regression analysis, absolute changes from baseline of RLP cholesterol and ALT after anagliptin treatment for 6 months ( RLP cholesterol and ALT) were independently correlated with ΔCAVI (R2=0.445).

Conclusion: The present study suggests that anagliptin may exert a beneficial effect on arterial stiffness in patients with T2DM, which is independent of its blood glucose-lowering property. Anagliptin may ameliorate arterial stiffness partly via reduction of RLP cholesterol and improvement of liver function.

Keywords:

Arterial stiffness, cardio-ankle vascular index, cardiovascular disease, DPP-4 inhibitors, diabetes mellitus.

Affiliation:

Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, Japan., Department of Medicine, Division of Cardiovascular Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan



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