Effects of luseogliflozin on arterial properties in patients with type 2 diabetes mellitus: The multicenter, exploratory LUSCAR study

Kario, Kazuomi; Okada, Kenta; Murata, Mitsunobu; Suzuki, Daisuke; Yamagiwa, Kayo; Abe, Yasuhisa; Usui, Isao; Tsuchiya, Norihiro; Iwashita, Chie; Harada, Noriko; Okawara, Yukie; Ishibashi, Shun

doi:10.1111/jch.13988

Cited by 29 publications

(29 citation statements)

References 54 publications

(52 reference statements)

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“…This suggests that other between‐trial differences and potential confounders could have contributed to the findings of different studies, and therefore, a class effect may still be possible. Certainly, SGLT2 inhibitors have a number of other beneficial actions that are likely to contribute to reductions in cardiovascular risk, including reductions in body weight and BP and improvement in glycemic control, 17,18 as were seen with luseogliflozin in our study 2 …”

supporting

confidence: 61%

“…We appreciate the comments from Dr Patoulias and colleagues 1 regarding our study investigating the effects of the sodium‐glucose cotransporter 2 (SGLT2) inhibitor, luseogliflozin, on arterial stiffness in patients with diabetes mellitus 2 . The results of our single‐arm study did not show any favorable effect of luseogliflozin on arterial stiffness, measured using the cardio‐ankle vascular index (CAVI) 2 . As a measure of arterial stiffness, CAVI is relatively independent of blood pressure (BP) and is now widely used in cardiovascular research and clinical practice 3–7 …”

mentioning

confidence: 99%

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Randomized, “head‐to‐head” studies comparing different SGLT2 inhibitors are definitely needed

Kario

Harada

Hoshide

2020

J of Clinical Hypertension

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supporting

confidence: 61%

mentioning

confidence: 99%

Randomized, “head‐to‐head” studies comparing different SGLT2 inhibitors are definitely needed

Kario

Harada

Hoshide

2020

J of Clinical Hypertension

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“…On the other hand, some potential conventional risk factors for arterial stiffness such as fasting hyperglycemia or insulin resistance [31,41,42] were not included in the multivariate regression analysis. Finally, multiple anti-diabetic agents including sodiumglucose cotransporter 2 inhibitors [43][44][45][46], but not all anti-diabetic agents [47], have been shown to improve arterial stiffness. In this regard, FLP-CGM-derived metrics related to intra-day glucose variability such as SD and MAGE, and metrics related to hyperglycemia such as TAR > 13.9 mmol/L and HBGI, were still significantly associated with high arterial stiffness, even after adjusting for the use of anti-diabetic agents (Additional file 1: Table S2).…”

Section: Discussionmentioning

confidence: 99%

Associations between continuous glucose monitoring-derived metrics and arterial stiffness in Japanese patients with type 2 diabetes

Wakasugi

Mita

Katakami

et al. 2021

Cardiovasc Diabetol

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Background Previous studies have suggested that high mean glucose levels and glycemic abnormalities such as glucose fluctuation and hypoglycemia accelerate the progression of atherosclerosis in patients with type 2 diabetes. Although continuous glucose monitoring (CGM) that could evaluate such glycemic abnormalities has been rapidly adopted, the associations between CGM-derived metrics and arterial stiffness are not entirely clear. Methods This exploratory cross-sectional study used baseline data from an ongoing prospective, multicenter, observational study with 5 years of follow-up. Study participants included 445 outpatients with type 2 diabetes and no history of apparent cardiovascular disease who underwent CGM and brachial-ankle pulse wave velocity (baPWV) measurement at baseline. Associations between CGM-derived metrics and baPWV were analyzed using multivariate regression models. Results In a linear regression model, all CGM-derived metrics were significantly associated with baPWV, but HbA1c was not. Some CGM-derived metrics related to intra-day glucose variability, hyperglycemia, and hypoglycemia remained significantly associated with baPWV after adjusting for possible atherosclerotic risk factors, including HbA1c. Based on baPWV ≥ 1800 cm/s as indicative of high arterial stiffness, multivariate logistic regression found that some CGM-derived metrics related to intra-day glucose variability and hyperglycemia are significantly associated with high arterial stiffness even after adjusting for possible atherosclerotic risk factors, including HbA1c. Conclusions Multiple CGM-derived metrics are significantly associated with baPWV and high arterial stiffness in patients with type 2 diabetes who have no history of apparent cardiovascular disease. These metrics might be useful for identifying patients at high risk of developing cardiovascular disease.

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“…The beneficial effects of SGLT2 inhibitors, such as tofogliflozin [ 12 ], empagliflozin [ 13 – 15 ], and canagliflozin [ 16 ], on arterial stiffness have been revealed in clinical studies using other indices of arterial stiffness, such as ambulatory arterial stiffness index [ 13 ], pulse pressure, mean arterial pressure, double product [ 16 ], and cardio-ankle vascular index (CAVI) [ 12 ]. However, several studies did not find beneficial effects of this class of antidiabetics on arterial stiffness [ 18 ]. Patoulias et al recently reviewed and summarized clinical studies on this topic and concluded that evidence on the effect of SGLT2 inhibitors on arterial stiffness remains limited and controversial [ 19 ].…”

Section: Discussionmentioning

confidence: 99%

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

Katakami

Mita

Yoshii

et al. 2021

Cardiovasc Diabetol

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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)

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Effects of luseogliflozin on arterial properties in patients with type 2 diabetes mellitus: The multicenter, exploratory LUSCAR study

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Cited by 29 publications

References 54 publications

Randomized, “head‐to‐head” studies comparing different SGLT2 inhibitors are definitely needed

Randomized, “head‐to‐head” studies comparing different SGLT2 inhibitors are definitely needed

Associations between continuous glucose monitoring-derived metrics and arterial stiffness in Japanese patients with type 2 diabetes

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

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