Effect of empagliflozin on endothelial function in patients with type 2 diabetes and cardiovascular disease: Results from the multicenter, randomized, placebo- controlled, double-blind EMBLEM trial

TY - JOUR

T1 - Effect of empagliflozin on endothelial function in patients with type 2 diabetes and cardiovascular disease

T2 - Results from the multicenter, randomized, placebo- controlled, double-blind EMBLEM trial

AU - Tanaka, Atsushi

AU - Shimabukuro, Michio

AU - MacHii, Noritaka

AU - Teragawa, Hiroki

AU - Okada, Yosuke

AU - Shima, Kosuke R.

AU - Takamura, Toshinari

AU - Taguchi, Isao

AU - Hisauchi, Itaru

AU - Toyoda, Shigeru

AU - Matsuzawa, Yasushi

AU - Tomiyama, Hirofumi

AU - Yamaoka-Tojo, Minako

AU - Yoshida, Hisako

AU - Sato, Yasunori

AU - Ikehara, Yumi

AU - Ueda, Shinichiro

AU - Higashi, Yukihito

AU - Node, Koichi

N1 - Funding Information: Acknowledgments. The authors thank the investigators, coordinators, and patients who participated in the trial. They also thank Takeshi Morimoto (Hyogo College of Medicine, Nishinomiya, Japan), Mitsuyoshi Urashima (Jikei University School of Medicine, Tokyo, Japan), and Takashi Nomiyama (Fukuoka University, Fukuoka, Japan), who served as members of the independent data and safety monitoring committee for the trial. Duality of Interest. This study was funded by Boehringer Ingelheim and Eli Lilly and Company. A.T. received modest honoraria from Astellas, AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Kowa, Merck, Mitsubishi Tanabe, Novo Nordisk, Taisho Toyama, Takeda, and Teijin. M.S. received an honorarium and endowed chair from Boehringer Ingelheim. H.T. received lecture fees from Bayer, Boehringer Ingelheim, Daichi Sankyo, Kowa, Takeda, Mitsubishi Tanabe, and Sanwa Kagaku Kenkyusho. Y.O. received lecture fees from Astellas, AstraZeneca, Merck Sharp & Dohme (MSD), Ono, Mitsubishi Tanabe, Bayer, Novo Nordisk, Eli Lilly and Company, Boehringer Ingelheim, Daiichi Sankyo, Kissei, Novartis, Kowa, and Sanwa Kagaku Kenkyusho and research Figure 1—The mean (SD) RHI at baseline and at the 24-week follow-up. RHI values were increased ([RHI at 24 weeks] − [RHI at baseline] . 0) after 24 weeks of treatment in 21 patients (45%) in the empagliflozin group (red lines) and 24 patients (47%) in the placebo group (blue lines). Funding Information: funds from Kowa and Mitsubishi Tanabe. T.T. received honoraria from MSD, Astellas, AstraZeneca, Mitsubishi Tanabe, Boehringer Ingelheim, Novo Nordisk, and Taisho Toyama; research funding from Kowa; and scholarships from Novartis, AstraZeneca, Astellas, and Novo Nordisk. M.Y-T. received honoraria from Bayer, Mitsubishi Tanabe, Itamar, MSD, Nippon Shinyaku, Boehringer Ingelheim, and Daiichi Sankyo. S.U. received research grants from Bristol-Myers Squibb and Kowa; nonpurpose research grants from Bristol-Myers Squibb, Chugai, MSD, Pfizer, and Takeda; and lecture fees from Boehringer Ingelheim and MSD. Y.H. received consulting fees from Mitsubishi Tanabe related to this study, as well as honoraria and grants from Teijin, BoehringerIngelheim,MSD,Sanofi,AstraZeneca, Kyowa Hakko Kirin, Takeda, Astellas, Daiichi Sankyo, Mochida, Nihon Kohden, Shionogi, Nippon Sigmax, Sanwa Kagaku Kenkyusho, Unex, and Kao and honoraria from Radiometer, Omron, Sumitomo Dainippon, Otsuka, Torii, Kowa, Fujiyakuhin, Amgen, Nippon Shinyaku, Itamar, Bayer, Eli Lilly and Company, and Ono. K.N. received honoraria from Eli Lilly and Company, Astellas,Ono,Takeda,DaiichiSankyo,Boehringer Ingelheim, MSD, Mitsubishi Tanabe, and AstraZeneca; research grants from Amgen, Teijin, Terumo, Mitsubishi Tanabe, Asahi Kasei, Astellas, Boehringer Ingelheim, and Bayer; and scholarships from Bayer, Daiichi Sankyo, Teijin, Astellas, Takeda, and Bristol-Myers Squibb. No other potential conflicts of interest relevant to this article were reported. Author Contributions. A.T. participated in the study design, operations, and analysis and interpretation of data and drafted the manuscript. M.S. helped to steer the study, collected and analyzed the data, and reviewed and edited the manuscript. N.M., H.T., Y.O., K.R.S., T.T, I.T., I.H., S.T., Y.M., H.T., M.Y.-T., H.Y., Y.S., Y.I., S.U., Y.H., and K.N. contributed to the study concept and design, study operations, data collection, and analysis and interpretation of data and critically reviewed and edited the manuscript. H.Y. contributed to the generation of the scheme for randomization. Y.S. contributed to the statistical analysis. S.U. and Y.H. helped to steer the study as research advisors and reviewed and edited the draft manuscript. K.N. was a principal investigator of the EMBLEM trial. K.N. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Prior Presentation. Parts of this study were presented in abstract form at the 55th Annual Meeting of the European Association for the

PY - 2019/10/1

Y1 - 2019/10/1

UR - http://www.scopus.com/inward/record.url?scp=85072546608&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85072546608&partnerID=8YFLogxK

U2 - 10.2337/dc19-1177

DO - 10.2337/dc19-1177

M3 - Letter

C2 - 31533913

AN - SCOPUS:85072546608

VL - 42

SP - E159-E161

JO - Diabetes Care

JF - Diabetes Care

SN - 1935-5548

IS - 10

ER -