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.