Delving into the Latest Updates on Tofogliflozin Hydrate with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Tofogliflozin, Tofogliflozin (USAN), Tofogliflozin anhydrous

+ [10]

Target

SGLT2

Mechanism

SGLT2 inhibitors(Sodium/glucose cotransporter 2 inhibitors)

Therapeutic Areas

Endocrinology and Metabolic DiseaseDigestive System DisordersUrogenital Diseases

Active Indication

Diabetes Mellitus, Type 2Nonalcoholic SteatohepatitisDiabetic Nephropathies

Inactive Indication-

Originator Organization

Chugai Pharmaceutical Co., Ltd.

Active Organization

Kowa Co., Ltd.Kowa Research Institute, Inc.

Shinshu University

Inactive Organization

Hoffmann-La Roche, Inc.

Drug Highest PhaseApproved

First Approval Date

JP (24 Mar 2014),

Diabetes Mellitus, Type 2

Regulation-

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Structure

Molecular FormulaC22H28O7

InChIKeyZXOCGDDVNPDRIW-NHFZGCSJSA-N

CAS Registry1201913-82-7

A Randomized, Open-Label, Six-Sequence, Three-Period Crossover Study to Demonstrate the Bioequivalence of Single Oral Administration of K-001 Relative to Single Oral Coadministration of Separate Tablets of K-877-ER Plus CSG452 in Healthy Adult Volunteers, and to Characterize the Food Effect on the Pharmacokinetics of K-001

The goal of this clinical trial is to demonstrate the bioequivalence of single oral administration of K-001 relative to single oral co-administration of separate tablets of K-877-ER and CSG452 in healthy adult volunteers, and to characterize the food effect on the Pharmacokinetics(PK) of K-001.

Start Date24 Feb 2023

Sponsor / Collaborator

Kowa Research Institute, Inc.

JPRN-jRCTs051220140 / RecruitingNot Applicable

The effect of tofogliflozin on cardiac structure focusing on myocardial fibrosis in type 2 diabetes patients with nonalcoholic fatty liver disease at risk for heart failure

Start Date23 Dec 2022

Sponsor / Collaborator-

JPRN-UMIN000049753 / RecruitingNot ApplicableIIT

A study to verify the efficacy of the selective SGLT2 inhibitor tofogliflozin hydrate in reducing nocturia - The VESTITO Study

Start Date19 Dec 2022

Sponsor / Collaborator-

100 Clinical Results associated with Tofogliflozin Hydrate

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100 Translational Medicine associated with Tofogliflozin Hydrate

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100 Patents (Medical) associated with Tofogliflozin Hydrate

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154

Literatures (Medical) associated with Tofogliflozin Hydrate

01 Jan 2024·BMJ open diabetes research & care

Effects of sodium-glucose cotransporter-2 (SGLT-2) inhibitors on serum uric acid levels in patients with chronic kidney disease: a systematic review and network meta-analysis

Review

Author: Zhang, Linli ; Zhong, Yifei ; Zhang, Fan ; Huang, Liuyan ; Bai, Yan ; Zhang, Xianwen

Elevated serum uric acid levels are an independent predictor of occurrence and development of chronic kidney disease (CKD) and are strongly associated with prognosis. Several clinical trials have demonstrated the benefits of sodium-glucose cotransporter-2 (SGLT-2) inhibitors. To evaluate and rank the effects and safety of various SGLT-2 for serum uric acid levels in patients with CKD. We performed a systematic PubMed, Embase, Scopus, and Web of Science search, including studies published before July 1, 2023. Two researchers independently extracted data on study characteristics and outcomes and assessed study quality using the Cochrane Collaboration’s risk of bias tool 2. Thegemtcpackage of R software was used to perform network meta-analysis within a Bayesian framework. The primary outcome was serum uric acid levels, and the secondary outcome was adverse events. Effect sizes are reported as standardized mean differences (SMDs), risk ratio (RR), and 95% CI, respectively. The certainty of evidence was evaluated using Grading of Recommendations, Assessment, Development and Evaluations (GRADE) criteria. Eight RCTs (9367 participants) were included in this meta-analysis. The results of the paired meta-analysis showed that SGLT-2 inhibitors significantly reduced serum uric acid levels in patients with CKD compared with the placebo group (SMD −0.22; 95% CI −0.42 to –0.03; GRADE: low). Pooled analysis of any adverse events reported in the included studies showed similar incidence rates in the SGLT-2 inhibitor and placebo groups (RR: 0.99; 95% CI 0.97 to 1.00; p=0.147; GRADE: high). Subgroup analysis showed a statistically significant difference only for tofogliflozin. Further network meta-analysis showed that dapagliflozin 10 mg and ipragliflozin 50 mg may be the most effective in reducing uric acid levels. SGLT-2 inhibitors significantly reduced serum uric acid levels in patients with CKD, and dapagliflozin 10 mg and ipragliflozin 50 mg may be the optimal dosages. SGLT-2 inhibitors hold great promise as an antidiabetic therapeutic option for patients with CKD who have elevated serum uric acid levels. PROSPERO registration number: CRD42023456581.

01 Jan 2024·Endocrinology, diabetes & metabolism

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

Article

Author: Kaku, Kohei ; Takamura, Toshinari ; Suganami, Hideki ; Kusakabe, Hiromi ; Nakamura, Hiroyuki ; Yoshida, Akihiro

Abstract:

Aims:

How 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 Methods:

We 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.

Results:

GGT 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.

Conclusions:

Reductions 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.

01 Jan 2024·Hypertension research : official journal of the Japanese Society of Hypertension

Sodium glucose cotransporter 2 inhibitor suppresses renal injury in rats with renal congestion

Article

Author: Mori, Takefumi ; Endo, Akari ; Ito, Hiroki ; Hirose, Takuo ; Takahashi, Kazuhiro ; Kamada, Ayaka ; Kimura, Tomoyoshi ; Ishikawa, Risa ; Sato, Shigemitsu ; Takahashi, Chika ; Oba-Yabana, Ikuko

Abstract:

Renal congestion is an issue of cardiorenal syndrome in patients with heart failure. Recent clinical and basic studies suggest a renoprotective potential of sodium–glucose cotransporter (SGLT) 2 inhibitors. However, the effect on renal congestion and its mechanism is not fully understood. Thus, we aimed to clarify the effect of SGLT inhibition in a renal congestion model. Renal congestion was induced in the left kidney of male Sprague-Dawley rats by ligation of the inferior vena cava between the renal veins. The SGLT2 inhibitor tofogliflozin or vehicle was orally administered daily from the day before IVC ligation until two days after surgery. On the third postoperative day, both the right control kidney and the left congested kidney were harvested and analyzed. Kidney weight and water content was increased, and renal injury and fibrosis were observed in the left congested kidney. Kidney weight gain and hydration were improved with tofogliflozin treatment. Additionally, this treatment effectively reduced renal injury and fibrosis, particularly in the renal cortex. SGLT2 expression was observed in the congested kidney, but suppressed in the damaged tubular cells. Molecules associated with inflammation were increased in the congested kidney and reversed by tofogliflozin treatment. Mitochondrial dysfunction provoked by renal congestion was also improved by tofogliflozin treatment. Tofogliflozin protects against renal damage induced by renal congestion. SGLT2 inhibitors could be a candidate strategy for renal impairment associated with heart failure.

100 Deals associated with Tofogliflozin Hydrate

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External Link

KEGG	Wiki	ATC	Drug Bank
D09978	Tofogliflozin Hydrate	A10BH	DB11824

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Diabetes Mellitus, Type 2	JP	Kowa Co., Ltd.	24 Mar 2014

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Nonalcoholic Steatohepatitis	Phase 2	US	Kowa Research Institute, Inc.	14 Nov 2022
Nonalcoholic Steatohepatitis	Phase 2	JP	Kowa Research Institute, Inc.	14 Nov 2022
Nonalcoholic Steatohepatitis	Phase 2	BG	Kowa Research Institute, Inc.	14 Nov 2022
Nonalcoholic Steatohepatitis	Phase 2	CA	Kowa Research Institute, Inc.	14 Nov 2022
Nonalcoholic Steatohepatitis	Phase 2	ES	Kowa Research Institute, Inc.	14 Nov 2022
Diabetic Nephropathies	Phase 2	JP	Kowa Co., Ltd.	22 Sep 2021
Diabetic Nephropathies	Phase 2	JP	Shinshu University	22 Sep 2021

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02649465 (Pubmed) Manual	Phase 4	Diabetes Mellitus, Type 2 \| Metabolic dysfunction-associated steatotic liver disease	40	Tofogliflozin	ybfnpdztyf(mhxycpjtaa) = The histological variables of steatosis (65%, P = 0.001), hepatocellular ballooning (55%, P = 0.002), and lobular inflammation (50%, P = 0.003) were improved in the tofogliflozin group, whereas only hepatocellular ballooning was improved in the glimepiride group (25%, P = 0.025). kgtihvjxym (pambceonis )	Positive	27 Jul 2022
				Glimepiride
ADA2021	Not Applicable	Anemia \| Polycythemia	774	Tofogliflozin (Anemia group)	rphvusbllv(klpwngimkt) = wspddjsmjx fbhlcgigex (ocaktrcwjr )	-	01 Jun 2021
				Tofogliflozin (Polycythemia group)	rphvusbllv(klpwngimkt) = adoptfckgy fbhlcgigex (ocaktrcwjr )
NCT00800176 (CTgov)	Phase 2	Diabetes Mellitus, Type 2	394	placebo (Placebo)	jiitirxxmu(amlqidpafv) = bshpibchpw cxnmozjimx (daqdmnjvvm, dvjzblyhuq - xcpomyholj) View more	-	18 Nov 2020
				RO4998452 (RO4998452 5mg)	jiitirxxmu(amlqidpafv) = bwpiftibfd cxnmozjimx (daqdmnjvvm, xqfpseujrj - youwgzbewy) View more
ADA2020	Not Applicable	Diabetes Mellitus, Type 2 Add-on	774	Tofogliflozin (Quartiles 1-3)	qrnhzvtefw(kwcjscemum) = xcfwcuqiht khhrljecjh (anumjqfwnw ) View more	-	01 Jun 2020
				Tofogliflozin (Quartile 4)	qrnhzvtefw(kwcjscemum) = bpsgasutbu khhrljecjh (anumjqfwnw ) View more
UTOPIA Trial (ADA2020)	Not Applicable	Diabetes Mellitus, Type 2	340	Tofogliflozin treatment group	reipynvujy(kppemlpcox) = skahsbnpkh qlucvsmlbu (zcyeudmvpo ) View more	-	01 Jun 2020
ADA2020	Not Applicable	Diabetes Mellitus, Type 2	12	Tofogliflozin	zpzxjhboon(pfrrisepvy) = zfqeeiewnx lhhmvdxuee (wiwkeuyeqe )	-	01 Jun 2020
				Tofogliflozin (No administration of drugs)	zpzxjhboon(pfrrisepvy) = npdkttjckj lhhmvdxuee (wiwkeuyeqe )
ADA2020	Not Applicable	-	166	Tofogliflozin	paolfywryb(kgplhoayni) = mlynbirstc fyidjpqrxq (zrfskxtnnn ) View more	-	01 Jun 2020
NCT02537834 (Pubmed \| J Diabetes Investig)	Phase 4	Diabetes Mellitus, Type 2 Add-on	67	Tofogliflozin 20 mg + GLP-1 receptor agonist	cpcufdcwdr(gtpqcdsqma) = ookfmhmatc uciqndtxti (pnmkitecgy )	Positive	01 Nov 2019
JPRN-UMIN000026161 (EASD2019)	Not Applicable	Third line	-	Tofogliflozin 20 mg/day	xcrlsmzqwx(ovykhcrioz) = Adverse events were observed in 27.3% patients in Tofogliflozin 20 mg/day and 29.0% in Glimepiride 0.5 mg/day. None of them were severe. There was one patient experienced hypoglycemia in Glimepiride 0.5 mg/day but none in Tofogliflozin 20 mg/day. tjgfugpoun (zaflmblbox )	Positive	19 Sep 2019
				Glimepiride 0.5 mg/day
EASD2018	Not Applicable	-	-	Tofogliflozin 10 mg	qyopoyfbah(gdbcptutvt) = sfgtabaglp sirjixuioo (wbozagqrqn ) View more	-	02 Oct 2018
				Tofogliflozin 20 mg	qyopoyfbah(gdbcptutvt) = nyxctumqeh sirjixuioo (wbozagqrqn ) View more