title: Sitagliptin Attenuates the Progression of Carotid Intima-Media Thickening in Insulin-Treated Patients With Type 2 Diabetes: The Sitagliptin Preventive Study of Intima-Media Thickness Evaluation (SPIKE): A Randomized Controlled Trial.
abstract: OBJECTIVE
  The effect of additional treatment with oral hypoglycemic agents on the progression of atherosclerosis remains unknown in insulin-treated patients with type 2 diabetes mellitus (T2DM). We assessed the effects of sitagliptin, a dipeptidyl peptidase 4 inhibitor, on carotid intima-media thickness (IMT) in T2DM.
  
  
  METHODS
  This prospective, randomized, open-label, blinded end point, multicenter, parallel-group, comparative study included 282 insulin-treated patients with T2DM free of a history of apparent cardiovascular diseases who were recruited at 12 clinical units and randomly allocated to either the sitagliptin group (n = 142) or the control group (n = 140). The primary outcomes were changes in mean and maximum IMT of the common carotid artery measured by echography at the end of a 104-week treatment period.
  
  
  RESULTS
  Sitagliptin had a more potent glucose-lowering effect compared with the conventional treatment (-0.5 ± 1.0% vs. -0.2 ± 0.9%; P = 0.004), without increasing hypoglycemic episodes or body weight. Changes in the mean and left maximum IMT, but not right maximum IMT, of the common carotid arteries were significantly greater after sitagliptin treatment compared with conventional treatment (-0.029 [SE 0.013] vs. 0.024 [0.013] mm [P = 0.005]; -0.065 [0.027] vs. 0.022 [0.026] mm [P = 0.021]; -0.007 [0.031] vs. 0.027 [0.031] mm [P = 0.45], respectively). Over 104 weeks, sitagliptin, but not conventional treatment, significantly reduced the mean IMT and left maximum IMT of common carotid arteries relative to the baseline.
  
  
  CONCLUSIONS
  Sitagliptin attenuated the progression of carotid IMT in insulin-treated patients with T2DM free of apparent cardiovascular disease compared with conventional treatment.
authors.affiliation: Department of Metabolism & Endocrinology, Juntendo University Graduate School of Medicine, Bunkyo-ku, 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, Suita, Osaka, Japan Department of Atherosclerosis and Metabolism, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Naoto
authors.initials: N
authors.lastname: Katakami
authors.affiliation: Shiraiwa Medical Clinic, Kashiwara, Osaka, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Shiraiwa
authors.affiliation: Department of Medicine, Diabetology & Endocrinology, Juntendo Tokyo Koto Geriatric Medical Center, Koto-ku, Tokyo, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Yoshii
authors.affiliation: Department of Medicine, Diabetology & Endocrinology, Juntendo Tokyo Koto Geriatric Medical Center, Koto-ku, Tokyo, Japan.
authors.forename: Tomio
authors.initials: T
authors.lastname: Onuma
authors.affiliation: Misaki Naika Clinic, Funabashi, Chiba, Japan.
authors.forename: Nobuichi
authors.initials: N
authors.lastname: Kuribayashi
authors.affiliation: Naka Memorial Clinic, Naka City, Ibaraki, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Osonoi
authors.affiliation: Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kaneto
authors.affiliation: Osaka Police Hospital, Tennoji-ku, Osaka, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Kosugi
authors.affiliation: Osaka General Medical Center, Sumiyoshi-ku, Osaka, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Umayahara
authors.affiliation: Kansai Rosai Hospital, Amagasaki-shi, Hyogo, Japan.
authors.forename: Tsunehiko
authors.initials: T
authors.lastname: Yamamoto
authors.affiliation: Diabetes Center, Sasebo Chuo Hospital, Sasebo, Nagasaki, Japan.
authors.forename: Kazunari
authors.initials: K
authors.lastname: Matsumoto
authors.affiliation: Department of Internal Medicine, Jiyugaoka Medical Clinic, Obihiro, Hokkaido, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Yokoyama
authors.affiliation: Ikeda Municipal Hospital, Ikeda, Osaka, Japan.
authors.forename: Mamiko
authors.initials: M
authors.lastname: Tsugawa
authors.affiliation: Department of Clinical Trial and Clinical Epidemiology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Gosho
authors.affiliation: Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Iichiro
authors.initials: I
authors.lastname: Shimomura
authors.affiliation: Department of Metabolism & Endocrinology, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Watada
mesh_terms: D000368:Aged; D050197:Atherosclerosis / Q000503:physiopathology / Q000517:prevention & control; D017536:Carotid Artery, Common / Q000000981:diagnostic imaging / Q000187:drug effects*; D059168:Carotid Intima-Media Thickness; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D018450:Disease Progression; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D007328:Insulin / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D000068900:Sitagliptin Phosphate / Q000494:pharmacology* / Q000627:therapeutic use; D017539:Tunica Intima / Q000000981:diagnostic imaging / Q000187:drug effects; D017540:Tunica Media / Q000000981:diagnostic imaging / Q000187:drug effects
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D007328:Insulin; D000068900:Sitagliptin Phosphate