{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T16:38:00Z","timestamp":1790959080857,"version":"4.1.0"},"reference-count":38,"publisher":"American Diabetes Association","issue":"3","license":[{"start":{"date-parts":[[2016,9,1]],"date-time":"2016-09-01T00:00:00Z","timestamp":1472688000000},"content-version":"vor","delay-in-days":217,"URL":"http:\/\/www.diabetesjournals.org\/site\/license"}],"funder":[{"name":"Japan Society for Patients Reported Outcome Research Fund from Mitsubishi Tanabe, Ono, and Novo Nordisk."}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2016,3,1]]},"abstract":"<jats:sec>\n                  <jats:title>OBJECTIVE<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESEARCH DESIGN AND METHODS<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>Sitagliptin had a more potent glucose-lowering effect compared with the conventional treatment (\u22120.5 \u00b1 1.0% vs. \u22120.2 \u00b1 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 (\u22120.029 [SE 0.013] vs. 0.024 [0.013] mm [P = 0.005]; \u22120.065 [0.027] vs. 0.022 [0.026] mm [P = 0.021]; \u22120.007 [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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSIONS<\/jats:title>\n                  <jats:p>Sitagliptin attenuated the progression of carotid IMT in insulin-treated patients with T2DM free of apparent cardiovascular disease compared with conventional treatment.<\/jats:p>\n               <\/jats:sec>","DOI":"10.2337\/dc15-2145","type":"journal-article","created":{"date-parts":[[2016,1,28]],"date-time":"2016-01-28T22:54:39Z","timestamp":1454021679000},"page":"455-464","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":116,"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)"],"prefix":"10.2337","volume":"39","author":[{"given":"Tomoya","family":"Mita","sequence":"first","affiliation":[{"name":"Department of Metabolism & Endocrinology, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoto","family":"Katakami","sequence":"additional","affiliation":[{"name":"Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan"},{"name":"Department of Atherosclerosis and Metabolism, Osaka University Graduate School of Medicine, Suita, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihiko","family":"Shiraiwa","sequence":"additional","affiliation":[{"name":"Shiraiwa Medical Clinic, Kashiwara, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidenori","family":"Yoshii","sequence":"additional","affiliation":[{"name":"Department of Medicine, Diabetology & Endocrinology, Juntendo Tokyo Koto Geriatric Medical Center, Koto-ku, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomio","family":"Onuma","sequence":"additional","affiliation":[{"name":"Department of Medicine, Diabetology & Endocrinology, Juntendo Tokyo Koto Geriatric Medical Center, Koto-ku, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuichi","family":"Kuribayashi","sequence":"additional","affiliation":[{"name":"Misaki Naika Clinic, Funabashi, Chiba, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Osonoi","sequence":"additional","affiliation":[{"name":"Naka Memorial Clinic, Naka City, Ibaraki, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideaki","family":"Kaneto","sequence":"additional","affiliation":[{"name":"Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keisuke","family":"Kosugi","sequence":"additional","affiliation":[{"name":"Osaka Police Hospital, Tennoji-ku, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutaka","family":"Umayahara","sequence":"additional","affiliation":[{"name":"Osaka General Medical Center, Sumiyoshi-ku, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsunehiko","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Kansai Rosai Hospital, Amagasaki-shi, Hyogo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazunari","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Diabetes Center, Sasebo Chuo Hospital, Sasebo, Nagasaki, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Yokoyama","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Jiyugaoka Medical Clinic, Obihiro, Hokkaido, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mamiko","family":"Tsugawa","sequence":"additional","affiliation":[{"name":"Ikeda Municipal Hospital, Ikeda, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiko","family":"Gosho","sequence":"additional","affiliation":[{"name":"Department of Clinical Trial and Clinical Epidemiology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iichiro","family":"Shimomura","sequence":"additional","affiliation":[{"name":"Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirotaka","family":"Watada","sequence":"additional","affiliation":[{"name":"Department of Metabolism & Endocrinology, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, 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