title: Alogliptin, a Dipeptidyl Peptidase 4 Inhibitor, Prevents the Progression of Carotid Atherosclerosis in Patients With Type 2 Diabetes: The Study of Preventive Effects of Alogliptin on Diabetic Atherosclerosis (SPEAD-A).
abstract: OBJECTIVE
  Recent experimental studies have shown that dipeptidyl peptidase 4 (DPP-4) inhibitors have antiatherosclerotic benefits in glucagon-like peptide 1-dependent and -independent manners. The current study investigated the effects of alogliptin, a DPP-4 inhibitor, on the progression of carotid atherosclerosis in patients with type 2 diabetes mellitus (T2DM).
  
  
  METHODS
  This prospective, randomized, open-label, blinded-end point, multicenter, parallel-group, comparative study included 341 patients with T2DM free of a history of apparent cardiovascular diseases recruited at 11 clinical units and randomly allocated to treatment with alogliptin (n = 172) or conventional treatment (n = 169). Primary outcomes were changes in mean common and maximum intima-media thickness (IMT) of the carotid artery measured by carotid arterial echography during a 24-month treatment period.
  
  
  RESULTS
  Alogliptin treatment had a more potent glucose-lowering effect than the conventional treatment (-0.3 ± 0.7% vs. -0.1 ± 0.8%, P = 0.004) without an increase of hypoglycemia. Changes in the mean common and the right and left maximum IMT of the carotid arteries were significantly greater after alogliptin treatment than after conventional treatment (-0.026 mm [SE 0.009] vs. 0.005 mm [SE 0.009], P = 0.022; -0.045 mm [SE 0.018] vs. 0.011 mm [SE 0.017], P = 0.025, and -0.079 mm [SE 0.018] vs. -0.015 mm [SE 0.018], P = 0.013, respectively).
  
  
  CONCLUSIONS
  Alogliptin treatment attenuated the progression of carotid IMT in patients with T2DM free of apparent cardiovascular disease compared with the conventional treatment.
authors.affiliation: Department of Metabolism & Endocrinology, Juntendo University Graduate School of Medicine, Tokyo, Japan Center for Molecular Diabetology, Juntendo University Graduate School of Medicine, Tokyo, Japan tom-m@juntendo.ac.jp.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Mita
authors.affiliation: Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Osaka, Japan Department of Metabolism and Atherosclerosis, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Naoto
authors.initials: N
authors.lastname: Katakami
authors.affiliation: Department of Medicine, Diabetology & Endocrinology, Juntendo Tokyo Koto Geriatric Medical Center, Tokyo, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Yoshii
authors.affiliation: Department of Medicine, Diabetology & Endocrinology, Juntendo Tokyo Koto Geriatric Medical Center, Tokyo, Japan.
authors.forename: Tomio
authors.initials: T
authors.lastname: Onuma
authors.affiliation: Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kaneto
authors.affiliation: Naka Memorial Clinic, Ibaraki, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Osonoi
authors.affiliation: Shiraiwa Medical Clinic, Osaka, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Shiraiwa
authors.affiliation: Osaka Police Hospital, Osaka, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Kosugi
authors.affiliation: Osaka General Medical Center, Osaka, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Umayahara
authors.affiliation: Kansai Rosai Hospital, Hyogo, Japan.
authors.forename: Tsunehiko
authors.initials: T
authors.lastname: Yamamoto
authors.affiliation: Internal Medicine, Jiyugaoka Medical Clinic, Hokkaido, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Yokoyama
authors.affiliation: Misaki Naika Clinic, Chiba, Japan.
authors.forename: Nobuichi
authors.initials: N
authors.lastname: Kuribayashi
authors.affiliation: Jinnouchi Hospital, Kumamoto, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Jinnouchi
authors.affiliation: Department of Clinical Trial and Clinical Epidemiology, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Gosho
authors.affiliation: Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Iichiro
authors.initials: I
authors.lastname: Shimomura
authors.affiliation: Department of Metabolism & Endocrinology, Juntendo University Graduate School of Medicine, Tokyo, Japan Center for Molecular Diabetology, Juntendo University Graduate School of Medicine, Tokyo, Japan Center for Therapeutic Innovations in Diabetes, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Watada
mesh_terms: D000368:Aged; D050197:Atherosclerosis / Q000517:prevention & control; D001786:Blood Glucose; D002339:Carotid Arteries / Q000187:drug effects / Q000473:pathology; D002340:Carotid Artery Diseases / Q000188:drug therapy*; D059168:Carotid Intima-Media Thickness; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000188:drug therapy; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D018450:Disease Progression; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007564:Japan; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000627:therapeutic use*; D011446:Prospective Studies; D014498:Uracil / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D010880:Piperidines; D014498:Uracil; D052216:Glucagon-Like Peptide 1; C520853:alogliptin