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Ōsaka, Japan

Katakami N.,Osaka University | Mita T.,Juntendo University | Yoshii H.,Juntendo University | Onuma T.,Juntendo University | And 12 more authors.
Journal of Atherosclerosis and Thrombosis | Year: 2013

Aim: Alogliptin, an efficacious inhibitor of DPP-4 that improves glycemic control, as well as the pancreatic beta-cell function, is now increasingly used to accomplish glycemic targets in type 2 diabetic patients. Interestingly, recent experimental studies have shown that alogliptin exerts anti-atherosclerotic effects in GLP-1-dependent and -independent manners. The aim of the present ongoing study is to investigate the preventive effects of alogliptin on the progression of atherosclerosis in type 2 diabetic subjects using the carotid intima-media thickness (IMT), an established marker of cardiovascular disease. Methods and Results: The Study of Preventive Effects of Alogliptin on Diabetic Atherosclerosis (SPEAD-A) is a prospective, randomized, open-label, blinded-endpoint, multicenter, parallel-group, comparative study. Between March 2011 and March 2012, 341 participants were recruited at 11 clinical sites, and were randomly allocated either to an alogliptin treatment group (172 patients) or a conventional treatment group (169 patients). The primary outcomes are the changes in the maximum and mean IMT of the common carotid artery during a 24-month treatment period, as measured by carotid arterial echography. The secondary outcomes include the changes in glycemic control, parameters related to beta-cell function and diabetic nephropathy, the occurrence of cardiovascular events and adverse events and biochemical measurements reflecting vascular function. Conclusions: This is the first study to address the effects of DPP-4 inhibitors on the progression of changes in the carotid IMT, with the patients without DPP-4 inhibitor treatment serving as a control group. The results will be available soon, and these findings are expected to provide clinical data that will be helpful in the prevention of diabetic atherosclerosis and subsequent cardiovascular disease.


Kaku K.,Kawasaki Medical School | Kiyosue A.,Tokyo Eki Center Building Clinic | Shiraiwa T.,Shiraiwa Medical Clinic | Kaneko S.,Red Cross | And 3 more authors.
Journal of Diabetes Investigation | Year: 2016

Introduction: The safety and efficacy of liraglutide in combination with an oral antidiabetic drug (OAD) compared with combination of two OADs were assessed in Japanese patients with type 2 diabetes. Materials and Methods: This was a 52-week, open-label, parallel-group trial in which patients whose type 2 diabetes was inadequately controlled with a single OAD (glinide, metformin, α-glucosidase inhibitor or thiazolidinedione) were randomized 2:1 to either pretrial OAD in combination with liraglutide 0.9 mg/day (liraglutide group; n = 240) or pretrial OAD in combination with an additional OAD (additional OAD group; n = 120). The primary outcome measure was the incidence of adverse events (AEs). Results: Overall, 86.3% of patients in the liraglutide group and 85.0% of patients in the additional OAD group experienced AEs; these were similar in nature and severity. Adverse event rates were 361 and 331 per 100 patient-years of exposure, respectively. Confirmed hypoglycemia was rare (seven episodes in two patients on liraglutide, and two in two patients on additional OAD). There were no reported pancreatitis events, and no unexpected safety signals were identified. Mean reductions in glycosylated hemoglobin were significantly greater in the liraglutide group than the additional OAD group [estimated mean treatment difference -0.27% (95% confidence interval (CI) -0.44, -0.09; P = 0.0026)]; reductions in mean fasting plasma glucose levels were also greater with liraglutide [estimated mean difference -5.47 mg/dL (-0.30 mmol/L; 95% CI: -10.83, -0.10; P = 0.0458)]. Conclusions: Liraglutide was well tolerated and effective as combination therapy with an OAD in Japanese patients with type 2 diabetes. © 2016 Asian Association for the Study of Diabetes and Wiley Publishing Asia Pty Ltd.


Mita T.,Juntendo University | Katakami N.,Osaka University | Shiraiwa T.,Shiraiwa Medical Clinic | Yoshii H.,Juntendo Tokyo Koto Geriatric Medical Center | And 13 more authors.
Diabetes Care | Year: 2016

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. Research Design and Methods This prospective, randomized, open-label, blinded end point, multicenter, parallelgroup, 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 (20.5 ± 1.0% vs. 20.2 ± 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 (20.029 [SE 0.013] vs. 0.024 [0.013] mm [P = 0.005]; 20.065 [0.027] vs. 0.022 [0.026] mm [P = 0.021]; 20.007 [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 maximumIMT 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. © 2016 by the American Diabetes Association.


Mita T.,Juntendo University | Katakami N.,Osaka University | Shiraiwa T.,Shiraiwa Medical Clinic | Yoshii H.,Juntendo Tokyo Koto Geriatric Medical Center | And 13 more authors.
Diabetology and Metabolic Syndrome | Year: 2014

Background: Sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, is currently used to achieve glycemic targets in patients with type 2 diabetes mellitus (T2DM). The addition of DPP-4 inhibitors to ongoing insulin therapy is expected to reduce insulin dosage, leading to a reduction in the frequency of hypoglycaemia and/or weight gain. Recent studies have demonstrated potential anti-atherosclerotic effects for DPP-4 inhibitors. The aim of the present ongoing study is to assess the effects of sitagliptin on the progression of atherosclerosis in patients with insulin-treated T2DM using carotid intima-media thickness (IMT), an established marker of cardiovascular disease. Methods and Design. The Sitagliptin Preventive study of Intima media thickness Evaluation (SPIKE) is a prospective, randomized, open-label, blinded-endpoint, multicenter, parallel-group, comparative study. Between February 2012 and September 2012, 282 participants who failed to achieve glycemic control despite insulin therapy were recruited at 12 clinics and randomly allocated to the sitagliptin group (n = 142) or the control group (n = 140). Primary outcomes are changes in maximum and mean IMT of the common carotid artery after 24-month treatment period measured by carotid arterial echography. Secondary outcomes include changes in glycemic control, parameters related to beta-cell function and diabetic nephropathy, occurrence of cardiovascular events and adverse events such as hypoglycaemia, and biochemical markers of vascular function. Discussion. The present study is designed to assess the effects of sitagliptin on the progression of carotid IMT. Results will be available in the near future, and the findings are expected to provide new strategy to prevent atherosclerosis in patients with insulin-treated T2DM. Clinical Trial Registration. UMIN000007396. © 2014 Mita et al.; licensee BioMed Central Ltd.


Mita T.,Juntendo University | Katakami N.,Osaka University | Yoshii H.,Juntendo Tokyo Koto Geriatric Medical Center | Onuma T.,Juntendo Tokyo Koto Geriatric Medical Center | And 12 more authors.
Diabetes Care | Year: 2016

OBJECTIVE Recent experimental studies have shown that dipeptidyl peptidase 4 (DPP-4) inhibitors have antiatherosclerotic benefits in glucagon-like peptide 1-dependent and independentmanners. 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). RESEARCH DESIGN AND METHODS This prospective, randomized, open-label, blinded-end point, multicenter, parallelgroup, 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 amore potent glucose-lowering effect than the conventional treatment (20.3 ± 0.7% vs. 20.1 ± 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 (20.026 mm [SE 0.009] vs. 0.005 mm [SE 0.009], P = 0.022; 20.045 mm [SE 0.018] vs. 0.011 mm [SE 0.017], P = 0.025, and 20.079 mm [SE 0.018] vs. 20.015 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. © 2016 by the American Diabetes Association.

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