title: 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.
abstract: 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.
  
  
  
  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.
  
  
  
  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 (ΔRLP cholesterol and ΔALT) were independently correlated with ΔCAVI (R2=0.445).
  
  
  
  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.
authors.affiliation: Department of Medicine, Division of Cardiovascular Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan. ntahara@med.kurume-u.ac.jp.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Tahara
authors.affiliation: Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, Japan. shoichi@med.kurume-u.ac.jp.
authors.forename: Sho-Ichi
authors.initials: SI
authors.lastname: Yamagishi
authors.forename: Munehisa
authors.initials: M
authors.lastname: Bekki
authors.forename: Norihiro
authors.initials: N
authors.lastname: Kodama
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Nakamura
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Sugiyama
authors.forename: Tamami
authors.initials: T
authors.lastname: Oshige
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kumashiro
authors.forename: Akihiro
authors.initials: A
authors.lastname: Honda
authors.forename: Atsuko
authors.initials: A
authors.lastname: Tahara
authors.forename: Sachiyo
authors.initials: S
authors.lastname: Igata
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Fukumoto
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000410:Alanine Transaminase / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D002784:Cholesterol / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007564:Japan; D008074:Lipoproteins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D013453:Sulfonylurea Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood*; D059289:Vascular Stiffness / Q000187:drug effects*
chemical_list: D000410:Alanine Transaminase; D015415:Biomarkers; D001786:Blood Glucose; D002784:Cholesterol; D018819:Dipeptidyl Peptidase 4; D054873:Dipeptidyl-Peptidase IV Inhibitors; D006442:Glycated Hemoglobin; D008074:Lipoproteins; D011743:Pyrimidines; D013453:Sulfonylurea Compounds; D014280:Triglycerides; C517652:hemoglobin A1c protein, human; C112017:remnant-like particle cholesterol; C057619:glimepiride; C042807:DPP4 protein, human; C583175:anagliptin