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