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Published in: Cardiovascular Diabetology 1/2021

Open Access 01-12-2021 | Arterial Occlusive Disease | Original investigation

Effect of tofogliflozin on arterial stiffness in patients with type 2 diabetes: prespecified sub-analysis of the prospective, randomized, open-label, parallel-group comparative UTOPIA trial

Authors: Naoto Katakami, Tomoya Mita, Hidenori Yoshii, Toshihiko Shiraiwa, Tetsuyuki Yasuda, Yosuke Okada, Keiichi Torimoto, Yutaka Umayahara, Hideaki Kaneto, Takeshi Osonoi, Tsunehiko Yamamoto, Nobuichi Kuribayashi, Kazuhisa Maeda, Hiroki Yokoyama, Keisuke Kosugi, Kentaro Ohtoshi, Isao Hayashi, Satoru Sumitani, Mamiko Tsugawa, Kayoko Ryomoto, Hideki Taki, Tadashi Nakamura, Satoshi Kawashima, Yasunori Sato, Hirotaka Watada, Iichiro Shimomura, On behalf of the UTOPIA study investigators

Published in: Cardiovascular Diabetology | Issue 1/2021

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Abstract

Background

Tofogliflozin, an SGLT2 inhibitor, is associated with favorable metabolic effects, including improved glycemic control and serum lipid profile and decreased body weight, visceral adipose tissue, and blood pressure (BP). This study evaluated the effects of tofogliflozin on the brachial-ankle pulse wave velocity (baPWV) in patients with type 2 diabetes (T2DM) without a history of apparent cardiovascular disease.

Methods

The using tofogliflozin for possible better intervention against atherosclerosis for type 2 diabetes patients (UTOPIA) trial is a prospective, randomized, open-label, multicenter, parallel-group, comparative study. As one of the prespecified secondary outcomes, changes in baPWV over 104 weeks were evaluated in 154 individuals (80 in the tofogliflozin group and 74 in the conventional treatment group) who completed baPWV measurement at baseline.

Results

In a mixed-effects model, the progression in the right, left, and mean baPWV over 104 weeks was significantly attenuated with tofogliflozin compared to that with conventional treatment (– 109.3 [– 184.3, – 34.3] (mean change [95% CI] cm/s, p = 0.005; – 98.3 [– 172.6, – 24.1] cm/s, p = 0.010; – 104.7 [– 177.0, – 32.4] cm/s, p = 0.005, respectively). Similar findings were obtained even after adjusting the mixed-effects models for traditional cardiovascular risk factors, including body mass index (BMI), glycated hemoglobin (HbA1c), total cholesterol, high-density lipoprotein (HDL)-cholesterol, triglyceride, systolic blood pressure (SBP), hypertension, smoking, and/or administration of drugs, including hypoglycemic agents, antihypertensive agents, statins, and anti-platelets, at baseline. The findings of the analysis of covariance (ANCOVA) models, which included the treatment group, baseline baPWV, and traditional cardiovascular risk factors, resembled those generated by the mixed-effects models.

Conclusions

Tofogliflozin significantly inhibited the increased baPWV in patients with T2DM without a history of apparent cardiovascular disease, suggesting that tofogliflozin suppressed the progression of arterial stiffness.
Trial Registration UMIN000017607. Registered 18 May 2015. (https://​www.​umin.​ac.​jp/​icdr/​index.​html)
Appendix
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Metadata
Title
Effect of tofogliflozin on arterial stiffness in patients with type 2 diabetes: prespecified sub-analysis of the prospective, randomized, open-label, parallel-group comparative UTOPIA trial
Authors
Naoto Katakami
Tomoya Mita
Hidenori Yoshii
Toshihiko Shiraiwa
Tetsuyuki Yasuda
Yosuke Okada
Keiichi Torimoto
Yutaka Umayahara
Hideaki Kaneto
Takeshi Osonoi
Tsunehiko Yamamoto
Nobuichi Kuribayashi
Kazuhisa Maeda
Hiroki Yokoyama
Keisuke Kosugi
Kentaro Ohtoshi
Isao Hayashi
Satoru Sumitani
Mamiko Tsugawa
Kayoko Ryomoto
Hideki Taki
Tadashi Nakamura
Satoshi Kawashima
Yasunori Sato
Hirotaka Watada
Iichiro Shimomura
On behalf of the UTOPIA study investigators
Publication date
01-12-2021
Publisher
BioMed Central
Published in
Cardiovascular Diabetology / Issue 1/2021
Electronic ISSN: 1475-2840
DOI
https://doi.org/10.1186/s12933-020-01206-1

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