TY - JOUR
T1 - Rationale, Design, and Baseline Characteristics of the Utopia Trial for Preventing Diabetic Atherosclerosis Using an SGLT2 Inhibitor
T2 - A Prospective, Randomized, Open-Label, Parallel-Group Comparative Study
AU - On behalf of the UTOPIA study investigators
AU - Katakami, Naoto
AU - Mita, Tomoya
AU - Yoshii, Hidenori
AU - Shiraiwa, Toshihiko
AU - Yasuda, Tetsuyuki
AU - Okada, Yosuke
AU - Umayahara, Yutaka
AU - Kaneto, Hideaki
AU - Osonoi, Takeshi
AU - Yamamoto, Tsunehiko
AU - Kuribayashi, Nobuichi
AU - Maeda, Kazuhisa
AU - Yokoyama, Hiroki
AU - Kosugi, Keisuke
AU - Ohtoshi, Kentaro
AU - Hayashi, Isao
AU - Sumitani, Satoru
AU - Tsugawa, Mamiko
AU - Ohashi, Makoto
AU - Taki, Hideki
AU - Nakamura, Tadashi
AU - Kawashima, Satoshi
AU - Sato, Yasunori
AU - Watada, Hirotaka
AU - Shimomura, Iichiro
N1 - Funding Information:
Disclosures. Naoto Katakami is a staff member of the endowed chair (Department of Metabolism and Atherosclerosis) established by funds from Kowa Co., Ltd., and has received research funds from MSD and lecture fees from Astellas Pharma Inc., AstraZeneca K.K., Boehringer Ingelheim, Daiichi Sankyo Inc., Dainip-pon Sumitomo Pharma Co., Eisai Co., Eli Lilly, Kowa Pharmaceutical Co., Kyowa Hakko Kirin Co. Ltd., Mitsubishi Tanabe Pharma Co., Novartis Pharmaceuticals, Novo Nordisk Pharma, Ono Pharmaceutical Co., Takeda Pharmaceutical Co., Sanofi-Aventis, and Shio-nogi & Co. Tomoya Mita has received lecture fees from Ono Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, scholarship donations from MSD K.K., Astellas Pharma Inc., AstraZeneca K.K., Ono Pharmaceutical Co., Ltd., Kyowa Hakko Kirin Co. Ltd., Sanofi-Aventis K.K., Daiichi Sankyo Company, Limited, Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited, Mitsubishi Tanabe Pharma Corporation, Terumo Corporation, Nippon Boehringer Ingelheim Co., Ltd., Novo Nordisk Pharma Ltd., Pfizer Japan Inc., Benefit One Health Care Inc., Mochida Pharmaceutical Co., Ltd., and Nitto Boseki Co., Ltd. as well as funds of endowed chair from MSD K.K., Takeda Pharmaceutical Company Limited. Toshihiko Shiraiwa has received lecture fees from Sanofi-Aventis K.K. and Takeda Pharmaceutical Company Limited and research funding from Novo Nordisk Pharma Ltd., Sanofi-Aventis K.K., Takeda Pharmaceutical Company Limited, AstraZeneca K.K., Nippon Boehringer Ingelheim Co., Ltd., and Mitsubishi Tanabe Pharma Corporation. Tetsuyuki Yasuda has received lecture fees from Nippon Boehringer Ingelheim Co., Ltd. and Sanofi-Aventis K.K. Yosuke Okada has received lecture fees from Astellas Pharma Inc., MSD K.K., Ono Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Bayer Holding Ltd., Novartis Pharmaceuticals Corp., Novo Nordisk Pharma Ltd., Eli Lilly Japan K.K., and Kissei Pharmaceutical Co., Ltd. as well as research funding from Kowa Pharmaceutical Co. Ltd. and Mit-subishi Tanabe Pharma Corporation. Hideaki Kaneto has received lecture fees from Nippon Boehringer Ingelheim Co., Ltd., Sanofi-Aventis K.K., Novo Nordisk Pharma Ltd., Eli Lilly Japan K.K., MSD K.K., Ono Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, Dai-ichi Sankyo Company, Limited, Mitsubishi Tanabe Pharma Corporation, AstraZeneca K.K., Astellas Pharma Inc., Novartis Pharmaceuticals Corp., and Sumitomo Dainippon Pharma Co.; scholarship donations from Novo Nordisk Pharma Ltd., Nippon Boehringer Ingelheim Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Ono Pharmaceutical Co., Ltd., Sanofi-Aventis K.K., Eli Lilly Japan K.K., Astellas Pharma Inc., Daiichi Sankyo Company, Limited, Mitsubishi Tanabe Pharma Corporation, MSD K.K., Takeda Pharmaceutical Company Limited, AstraZeneca K.K., Mochida Pharmaceutical Co., Ltd., Taisho Toyama Pharmaceutical Co., Kissei Pharmaceutical Co., Ltd., and Kyowa Hakko Kirin Co. Ltd. Takeshi Osonoi has received lecture fees from Takeda Pharmaceutical Company Limited, Astellas Pharma Inc., Novo Nordisk Pharma Ltd., and Sanwa Kagaku Kenkyusho Co., Ltd.; manuscript fees from Sanwa Kagaku Kenkyusho Co., Ltd.; and research funding from Takeda Pharmaceutical Company Limited, Novo Nordisk Pharma Ltd., Astellas Pharma Inc., Sanwa Kagaku Kenkyusho Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Nippon Boehringer Ingelheim Co., Ltd., Taisho Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Daiichi Sankyo Company, Limited, Bayer Holding Ltd., Kowa Pharmaceutical Co. Ltd., and AbbVie Inc. Nobuichi Kuribayashi has received lecture fees from Takeda Pharmaceutical Company Limited, Sanofi-Aventis K.K., Novo Nordisk Pharma Ltd., MSD K.K., and Mitsubishi Tanabe Pharma Corporation. Satoru Sumitani has received lecture fees from Sumitomo Dainippon Pharma Co., Ltd. Yasunori Sato has received lecture fees from Siemens K.K. Hirotaka Watada has received lecture fees from Sanofi-Aventis K.K., MSD K.K., Astellas Pharma Inc., Takeda Pharmaceutical Company Limited, Mitsubishi Tanabe Pharma Corporation, AstraZeneca K.K., Nippon Boehringer Ingelheim Co., Ltd., Eli Lilly Japan K.K., Novo Nordisk Pharma Ltd., Sanwa Kagaku Kenkyusho Co., Ltd., Kowa Co., Ltd., Novartis Pharmaceuticals Corp., Daiichi Sankyo Company, Limited, Kyowa Hakko Kirin Co. Ltd., Ono Pharmaceutical Co., Ltd., and Kissei Pharmaceutical Co., Ltd.; research funding from Novartis Pharmaceuticals Corp., Eli Lilly Japan K.K., scholarship donations from MSD K.K., Astellas Pharma Inc., AstraZeneca K.K., Abbot Japan Co., Ltd., Ono Pharmaceutical Co., Ltd., Kissei Pharmaceutical Co., Ltd., Kyowa Hakko Kirin Co. Ltd., Kowa Pharmaceutical Co. Ltd., Sanofi-Aventis K.K., Sanwa Kagaku Kenkyusho Co., Ltd., Johnson & Johnson K.K., Daiichi Sankyo Company, Limited, Sumitomo Dainip-pon Pharma Co., Ltd., Terumo Corporation, Taisho Toyama Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, Mitsubishi Tanabe Pharma Corporation, Nitto Boseki Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Novartis Pharmaceuticals Corp., Novo Nordisk Pharma Ltd., Bayer Holding Ltd., Pfizer Japan Inc., Bristol-Myers Squibb K.K., Benefit one Health care Inc., and Mochida Pharmaceutical Co., Ltd.; and funds of endowed chair from MSD K.K. and Takeda Pharmaceutical Company Limited. Iichiro Shimomura has received lecture fees from Astellas Pharma Inc., AstraZeneca K.K., MSD K.K., Ono Pharmaceutical Co., Kyowa Hakko Kirin Co., Kowa Pharmaceutical Co., Sanofi K.K., Sanwa Kagaku Kenkyusho Co., Daiichi Sankyo Co., Takeda Pharma K.K., Mit-subishi Tanabe Pharma Co., Teijin Pharma, Eli Lilly Japan K.K., Nippon Boehringer Ingelheim Co., Novartis Pharma K.K., Novo Nordisk Pharma, Bayer Yakuhin, Pfizer Japan Inc., Bristol-Myers K.K., Mochida Pharmaceutical Co., Shionogi & Co., Taisho Toyama Pharmaceutical Co., and Shionogi & Co.; and research funds from Astellas Pharma Inc., AstraZeneca K.K., Eisai Co., MSD K.K, Otsuka Pharmaceutical Co., Ono Pharmaceutical Co., Kaken Pharmaceutical Co., Kissei Pharmaceutical Co., Kyowa Hakko Kirin Co., Sanofi K.K., Shionogi & Co., Daiichi Sankyo Co., Dainippon Sumitomo Pharma Co., Takeda Pharma K.K., Mitsubishi Tanabe Pharma Co., Teijin Pharma, Nippon Boehringer Ingel-heim Co., Novartis Pharma K.K., Novo Nordisk Pharma, Pfizer Japan Inc., Bristol-Myers K.K., Mochida Pharmaceutical Co., Eli Lilly Japan K.K, Kowa Co., Ltd., Kowa Pharmaceutical Co., and Taisho Toyama Pharmaceutical Co. Hide-nori Yoshii, Yutaka Umayahara, Tsunehiko Yamamoto, Kazuhisa Maeda, Hiroki Yokoyama, Keisuke Kosugi, Kentaro Ohtoshi, Isao Hayashi, Mamiko Tsugawa, Makoto Ohashi, Hideki Taki, Tadashi Nakamura, and Satoshi Kawashima declare that they have no conflict of interest.
Publisher Copyright:
© 2017, The Author(s).
PY - 2017/10/1
Y1 - 2017/10/1
N2 - Introduction: Sodium-glucose co-transporter-2 (SGLT2) inhibitors are anti-diabetic agents that improve glycemic control with a low risk of hypoglycemia and ameliorate a variety of cardiovascular risk factors. The aim of the ongoing study described herein is to investigate the preventive effects of tofogliflozin, a potent and selective SGLT2 inhibitor, on the progression of atherosclerosis in subjects with type 2 diabetes (T2DM) using carotid intima-media thickness (IMT), an established marker of cardiovascular disease (CVD), as a marker. Methods: The Study of Using Tofogliflozin for Possible better Intervention against Atherosclerosis for type 2 diabetes patients (UTOPIA) trial is a prospective, randomized, open-label, blinded-endpoint, multicenter, and parallel-group comparative study. The aim was to recruit a total of 340 subjects with T2DM but no history of apparent CVD at 24 clinical sites and randomly allocate these to a tofogliflozin treatment group or a conventional treatment group using drugs other than SGLT2 inhibitors. As primary outcomes, changes in mean and maximum IMT of the common carotid artery during a 104-week treatment period will be measured by carotid echography. Secondary outcomes include changes in glycemic control, parameters related to β-cell function and diabetic nephropathy, the occurrence of CVD and adverse events, and biochemical measurements reflecting vascular function. Conclusion: This is the first study to address the effects of SGLT2 inhibitors on the progression of carotid IMT in subjects with T2DM without a history of CVD. The results will be available in the very near future, and these findings are expected to provide clinical data that will be helpful in the prevention of diabetic atherosclerosis and subsequent CVD. Funding: Kowa Co., Ltd. Clinical Trial Registration: UMIN000017607.
AB - Introduction: Sodium-glucose co-transporter-2 (SGLT2) inhibitors are anti-diabetic agents that improve glycemic control with a low risk of hypoglycemia and ameliorate a variety of cardiovascular risk factors. The aim of the ongoing study described herein is to investigate the preventive effects of tofogliflozin, a potent and selective SGLT2 inhibitor, on the progression of atherosclerosis in subjects with type 2 diabetes (T2DM) using carotid intima-media thickness (IMT), an established marker of cardiovascular disease (CVD), as a marker. Methods: The Study of Using Tofogliflozin for Possible better Intervention against Atherosclerosis for type 2 diabetes patients (UTOPIA) trial is a prospective, randomized, open-label, blinded-endpoint, multicenter, and parallel-group comparative study. The aim was to recruit a total of 340 subjects with T2DM but no history of apparent CVD at 24 clinical sites and randomly allocate these to a tofogliflozin treatment group or a conventional treatment group using drugs other than SGLT2 inhibitors. As primary outcomes, changes in mean and maximum IMT of the common carotid artery during a 104-week treatment period will be measured by carotid echography. Secondary outcomes include changes in glycemic control, parameters related to β-cell function and diabetic nephropathy, the occurrence of CVD and adverse events, and biochemical measurements reflecting vascular function. Conclusion: This is the first study to address the effects of SGLT2 inhibitors on the progression of carotid IMT in subjects with T2DM without a history of CVD. The results will be available in the very near future, and these findings are expected to provide clinical data that will be helpful in the prevention of diabetic atherosclerosis and subsequent CVD. Funding: Kowa Co., Ltd. Clinical Trial Registration: UMIN000017607.
KW - Atherosclerosis
KW - Diabetes
KW - Intima-media thickness
KW - SGLT2 inhibitor
KW - Tofogliflozin
UR - http://www.scopus.com/inward/record.url?scp=85030870283&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85030870283&partnerID=8YFLogxK
U2 - 10.1007/s13300-017-0292-1
DO - 10.1007/s13300-017-0292-1
M3 - Article
AN - SCOPUS:85030870283
VL - 8
SP - 999
EP - 1013
JO - Diabetes Therapy
JF - Diabetes Therapy
SN - 1869-6953
IS - 5
ER -