The effect of sodium-glucose cotransporter 2 inhibitor (tofogliflozin) on renal tubular damage in diabetic patients without albuminuria

Shimohata, Homare; Iwaki, Yoshiki; Yamashita, Marina Mayumi; Ohgi, Kentaro; Maruyama, Hiroshi; Takayasu, Mamiko; Hirayama, Kouichi; Kobayashi, Masaki

doi:10.1007/s11255-021-03064-6

Cited by 4 publications

(4 citation statements)

References 28 publications

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“…Dapagliflozin was also clinically assessed to reduce HbA1c, weight and SBP in patients with T2DM and HF [ 71 ]. It was proven that HbA1c can be significantly reduced with canagliflozin [ 72 ] or tofogliflozin [ 73 ] as well. Following in vivo studies in mice, dapagliflozin showed a hypoglycaemic effect after 8 or 12 weeks of treatment and reduced insulin, triglyceride and cardiac BNP levels [ 74 , 75 , 76 ].…”

Section: Sglt-2is In Dc—the Overview Of Research Resultsmentioning

confidence: 99%

The Importance of SGLT-2 Inhibitors as Both the Prevention and the Treatment of Diabetic Cardiomyopathy

et al. 2022

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According to the 2021 report of the International Diabetes Federation (IDF), there have been approximately 573 million cases of type 2 diabetes mellitus (T2DM) among adults, which sets the disease as a major concern in healthcare worldwide. The development of T2DM is strongly promoted by unhealthy lifestyle factors associated with urbanization and western civilization. The disease is associated with a broad list of systemic complications that can result in premature death, disability and significantly reduced quality of life. The most dramatic in their consequences are cardiovascular complications of T2DM. Our work focuses on one such complication that is specific for diabetes, named diabetic cardiomyopathy (DC). In this condition cardiac dysfunction occurs despite the absence of underlying hypertension, coronary artery disease and valvular disease, which suggest a leading role for metabolic disturbances as a cause. We aimed to establish the role of relatively new hypoglycaemic drugs that have taken the medical world by storm with their broad pleiotropic effects—SGLT-2 inhibitors—in the prevention and treatment of DC at any stage.

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Section: Sglt-2is In Dc—the Overview Of Research Resultsmentioning

confidence: 99%

The Importance of SGLT-2 Inhibitors as Both the Prevention and the Treatment of Diabetic Cardiomyopathy

et al. 2022

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“…This is because the interstitium, which includes the renal tubules but not the glomeruli, makes up a significant portion of the kidney's anatomy [32]. It has been reported that tofogliflozin suppresses tubulointerstitial injury [33][34][35]. Shimomura et al reported that urinary neutrophil gelatinase-associated lipocalin (NGAL), which is a tubular damage marker, tended to be decreased after the administration of tofogliflozin in 14 non-albuminuric patients with type 2 diabetes [33].…”

Section: Plos Onementioning

confidence: 99%

“…It has been reported that tofogliflozin suppresses tubulointerstitial injury [33][34][35]. Shimomura et al reported that urinary neutrophil gelatinase-associated lipocalin (NGAL), which is a tubular damage marker, tended to be decreased after the administration of tofogliflozin in 14 non-albuminuric patients with type 2 diabetes [33]. Nunoi et al reported that both urinary N-acetyl-beta-d-glucosaminidase (NAG) and β2-microglobulin were decreased after the initiation of tofogliflozin, with significant negative correlations seen between changes in these markers and their corresponding baseline values in patients with type 2 diabetes and macroalbuminuria based on an integrated analysis of four phases 2 and 3 studies [34].…”

Section: Plos Onementioning

confidence: 99%

Changes in the estimated glomerular filtration rate and predictors of the renal prognosis in Japanese patients with type 2 diabetes: A retrospective study during the 12 months after the initiation of tofogliflozin

Ito,

Inoue,

Izutsu

et al. 2023

PLoS ONE

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Background The changes in the estimated glomerular filtration rate (eGFR) and predictors of the renal prognosis were retrospectively assessed over the 12 months after the initiation of tofogliflozin, which has the shortest half-life among sodium-glucose cotransporter 2 (SGLT2) inhibitors, in Japanese patients with type 2 diabetes and renal impairment. Methods In total, 158 patients treated with tofogliflozin between 2019 and 2021 were studied as the safety analysis set. One hundred and thirty subjects whose medication was continued over 12 months were investigated as the full analysis set. The subjects were divided into two groups based on the eGFR: normal- (eGFR ≥60 mL/min/1.73 m2, n = 87) and low- (eGFR <60 mL/min/1.73 m2, n = 43) eGFR groups. Results The body weight, blood pressure, urinary protein excretion, and serum uric acid concentration decreased from baseline in both eGFR groups while the hemoglobin level increased. The eGFR did not significantly differ over time, except for the initial dip (-4.3±9.6 mL/min/1.73 m2 in the normal-eGFR group and -1.5±5.3 mL/min/1.73 m2 in the low-eGFR group). The change in the eGFR at 12 months after the initiation of tofogliflozin was -1.9±9.0 mL/min/1.73 m2 and 0.2±6.0 mL/min/1.73 m2 in the normal- and low-eGFR group, respectively. In the normal-eGFR group, the change in the eGFR showed a significant negative correlation with the HbA1c and eGFR at baseline, according to a multiple regression analysis. In the low-eGFR group, the change in the eGFR showed a significant negative correlation with urate-lowering agent use. The frequencies of adverse events specific for SGLT2 inhibitors were not significantly different between the normal- and low-eGFR groups. Conclusions Tofogliflozin may preserve renal function in the medium term in patients with type 2 diabetes and kidney impairment without an increase in specific adverse events.

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“…The addition of SGLT2 inhibitors to angiotensin-converting enzyme inhibitor ramipril resulted in the lowering of urinary 8-isoprostane concentration compared to the addition of placebo to ramipril in the randomized, double-blind, placebo-controlled, crossover trial of Lytvyn et al [ 90 ]. Moving to a study of 14 non-albuminuric patients with diabetes mellitus, no differences in the urinary oxidative stress marker, 8-hydroxydeoxyguanosine, were noted during the 1-, 3-, and 6-month follow-up [ 91 ]. Last but not least, in a circulating proteomics analysis of 1134 patients included in the EMPEROR-PRESERVED and EMPEROR-REDUCED trials, a differential expression of proteins associated with oxidative stress (angiopoietin-related protein 4, insulin-like growth factor-binding protein 4) was documented [ 92 ].…”

Section: Antioxidant Pharmacotherapies In Cardiorenal Diseasesmentioning

confidence: 99%

Oxidative Stress Management in Cardiorenal Diseases: Focus on Novel Antidiabetic Agents, Finerenone, and Melatonin

Theofilis

Vordoni

Kalaitzidis

2022

Life

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Oxidative stress is characterized by excessive production of reactive oxygen species together with exhausted antioxidant defenses. This constitutes a main pathophysiologic process that is implicated in cardiovascular and renal diseases. In particular, enhanced oxidative stress may lead to low-density lipoprotein accumulation and oxidation, endothelial cell activation, adhesion molecule overexpression, macrophage activation, and foam cell formation, promoting the development and progression of atherosclerosis. The deleterious kidney effects of oxidative stress are numerous, including podocytopathy, mesangial enlargement, renal hypertrophy, tubulointerstitial fibrosis, and glomerulosclerosis. The prominent role of oxidative mechanisms in cardiorenal diseases may be counteracted by recently developed pharmacotherapies such as novel antidiabetic agents and finerenone. These agents have demonstrated significant antioxidant activity in preclinical and clinical studies. Moreover, the use of melatonin as a treatment in this field has been experimentally investigated, with large-scale clinical studies being awaited. Finally, clinical implications and future directions in this field are presented.

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The effect of sodium-glucose cotransporter 2 inhibitor (tofogliflozin) on renal tubular damage in diabetic patients without albuminuria

Cited by 4 publications

References 28 publications

The Importance of SGLT-2 Inhibitors as Both the Prevention and the Treatment of Diabetic Cardiomyopathy

The Importance of SGLT-2 Inhibitors as Both the Prevention and the Treatment of Diabetic Cardiomyopathy

Changes in the estimated glomerular filtration rate and predictors of the renal prognosis in Japanese patients with type 2 diabetes: A retrospective study during the 12 months after the initiation of tofogliflozin

Oxidative Stress Management in Cardiorenal Diseases: Focus on Novel Antidiabetic Agents, Finerenone, and Melatonin

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