Effect of Renal Impairment on the Pharmacokinetics and Pharmacodynamics of Tofogliflozin (A SELECTIVE SGLT2 Inhibitor) in Patients with Type 2 Diabetes Mellitus

Ikeda, Sachiya; Takano, Yasuki; Schwab, Dietmar; Portron, Agnès; Kasahara-Ito, Nahoko; Saito, Tomohisa; Iida, Satofumi

doi:10.1055/a-0662-0209

Cited by 11 publications

(4 citation statements)

References 26 publications

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“…Taking the glucose-lowering mechanism such as an enhancement of urinary glucose excretion by SGLT2i into account, the lower renal function could be a negative factor for the decrease of HbA1c level in line with previous reports [ 5 , 13 ]. It is of interest, however, a significant weight loss was observed even in patients with moderate renal impairment [ 14 ], suggesting other mechanisms than glucose excretion into urine might have occurred. Thus, the enhancement of lipolysis after the administration of SGLT2i could be the most likely scenario as a potential mechanism for weight reduction independent of glucose-lowering effect.…”

Section: Discussionmentioning

confidence: 99%

Beneficial effects of SGLT2 inhibitor on metabolic inflexibility and visceral fat amount in animal model of obese type 2 diabetes

Hara

Sakai

Tajiri

et al. 2022

Heliyon

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Section: Discussionmentioning

confidence: 99%

Beneficial effects of SGLT2 inhibitor on metabolic inflexibility and visceral fat amount in animal model of obese type 2 diabetes

Hara

Sakai

Tajiri

et al. 2022

Heliyon

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“…Details of these studies and their results, along with patient inclusion and exclusion criteria, were previously reported 14,16 . The CSG006JP study (tofogliflozin 40 mg as monotherapy or an add‐on to sulfonylurea or dipeptidyl peptidase‐4 inhibitor) was a 24‐week, multicentre, open‐label trial 17 . Individual‐level data from the 24‐ or 52‐week core treatment periods of each study were used in this pooled analysis.…”

Section: Methodsmentioning

confidence: 99%

“… 14 , 16 The CSG006JP study (tofogliflozin 40 mg as monotherapy or an add‐on to sulfonylurea or dipeptidyl peptidase‐4 inhibitor) was a 24‐week, multicentre, open‐label trial. 17 Individual‐level data from the 24‐ or 52‐week core treatment periods of each study were used in this pooled analysis. Details of each study with the main patient inclusion criteria are summarized in Table S1 .…”

Section: Methodsmentioning

confidence: 99%

Reductions in liver enzymes are associated with anti‐hyperglycaemic and anti‐obesity effects of tofogliflozin in people with type 2 diabetes: Post‐hoc analyses

Takamura,

Kaku,

Yoshida

et al. 2023

Endocrino Diabet & Metabol

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AimsHow the pathology of type 2 diabetes (T2D), including hyperglycaemia and obesity, affects liver enzymes has not been clinically demonstrated. Thus, we compared time courses of gamma‐glutamyltransferase (GGT) and alanine aminotransferase (ALT) with those of fasting plasma glucose (FPG) and body weight (BW) during treatment with the SGLT2 inhibitor tofogliflozin for T2D.Materials and MethodsWe post‐hoc analysed preexisting data on 1046 people with T2D administered tofogliflozin or placebo for 24 weeks in four tofogliflozin studies. First, time courses of percent changes in variables during the intervention were analysed using a mixed effect model to explore the similarity of the time courses and to evaluate time‐treatment interactions. Second, clinical factors related to the percent changes in GGT and ALT were clarified using multivariate analyses.ResultsGGT levels and FPG values rapidly and significantly decreased via tofogliflozin as early as week 4, with decreases maintained until week 24. Conversely, BW and ALT decreased progressively until week 24. Time courses of FPG (p = .365, time‐treatment interaction) and GGT (p = .510) reductions were parallel between tofogliflozin and placebo from weeks 4 to 24, while BW and ALT reductions (p < .001, respectively) were not. Reductions in GGT at week 24 were associated with reductions in FPG and BW at week 24, whereas ALT reductions were only associated with reductions in BW.ConclusionsReductions in GGT and ALT were associated with the anti‐hyperglycaemic and anti‐obesity effects of tofogliflozin, respectively, in people with T2D. Therefore, GGT and ALT may be surrogate markers for hyperglycaemia and obesity in T2D.

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“…Tofogliflozin reduces body fat mass leading to improvement in insulin sensitivity and peripheral glucose uptake (Matsuba, Matsuba, Shimokawa, Nagai, & Tanaka, ). Renal function does not affect the pharmacokinetics of tofogliflozin; hence, dose adjustment is not required for T2DM patients with renal disorders (Ikeda et al, ). Arterial stiffness was improved following a switch from DPP‐4 inhibitors to tofogliflozin, which may be due to improvements in liver function (N. Tahara et al, ).…”

Section: Phlorizinmentioning

confidence: 99%

Natural products with SGLT2 inhibitory activity: Possibilities of application for the treatment of diabetes

Moradi‐Marjaneh

Paseban

Sahebkar

2019

Phytotherapy Research

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Diabetes mellitus currently affects as many as 400 million people worldwide, creating a heavy economic burden and stretching health care resources. A dysfunction of glucose homeostasis underlies the disease. Despite advances in the treatment of diabetes, many patients still suffer from complications and side effects; hence, development of more effective treatments for diabetes is still desirable. SGLT2 is the principle cotransporter involved in glucose reabsorption in the kidney. SGLT2 inhibition reduces glucose reabsorption by the kidney and ameliorates plasma glucose concentration. The interest in natural products that can be used for the inhibition of SGLT2 is growing. The flavonoid phlorizin, which can be isolated from the bark of apple trees, has been used as lead structure due to its inhibitory activity of SGLT1 and SGLT2. Some phlorizin-derived synthetic compounds, including canagliflozin, dapagliflozin, empagliflozin, ipragliflozin, and ertugliflozin, are approved by the food and drug administration to treat type 2 diabetes mellitus (T2DM), whereas others are under clinical trials investigation. In addition, other natural product-derived compounds have been investigated for their ability to improve blood glucose control.The present review summarizes the natural products with SGLT2 inhibitory activity, and the synthetic compounds obtained from them, and discusses their application for the treatment of diabetes.

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Effect of Renal Impairment on the Pharmacokinetics and Pharmacodynamics of Tofogliflozin (A SELECTIVE SGLT2 Inhibitor) in Patients with Type 2 Diabetes Mellitus

Abstract: Single and multiple administrations of tofogliflozin were generally well tolerated in T2DM patients with various renal functions. As far as investigated here, these studies indicate no dose adjustment is required for patients with renal impairment.

Cited by 11 publications

References 26 publications

Beneficial effects of SGLT2 inhibitor on metabolic inflexibility and visceral fat amount in animal model of obese type 2 diabetes

Beneficial effects of SGLT2 inhibitor on metabolic inflexibility and visceral fat amount in animal model of obese type 2 diabetes

Reductions in liver enzymes are associated with anti‐hyperglycaemic and anti‐obesity effects of tofogliflozin in people with type 2 diabetes: Post‐hoc analyses

Natural products with SGLT2 inhibitory activity: Possibilities of application for the treatment of diabetes

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