Delving into the Latest Updates on Luseogliflozin Hydrate with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Luseogliflozin, Luseogliflozin hydrate (JAN)

+ [3]

Target

SGLT2

Mechanism

SGLT2 inhibitors(Sodium/glucose cotransporter 2 inhibitors)

Therapeutic Areas

Endocrinology and Metabolic Disease

Active Indication

Diabetes Mellitus, Type 2

Inactive Indication-

Originator Organization

Taisho Pharmaceutical Co., Ltd.

Active Organization

Taisho Pharmaceutical Co., Ltd.

Inactive Organization-

Drug Highest PhaseApproved

First Approval Date

JP (24 Mar 2014),

Diabetes Mellitus, Type 2

Regulation-

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Structure

Molecular FormulaC23H30O6S

InChIKeyWHSOLWOTCHFFBK-ZQGJOIPISA-N

CAS Registry898537-18-3

AbstractBackgroundLuseogliflozin, a sodium–glucose cotransporter 2 inhibitor, potentially exerts pleiotropic effects on the liver. However, the sufficient evidence is still lacking. We aimed to investigate the effects of luseogliflozin on hepatic steatosis, fibrosis, and cardiometabolic risk factors in diabetic patients by a pooled meta-analysis.MethodsIn this pooled meta-analysis, we enrolled diabetic patients who participated in phase III clinical trials of luseogliflozin (luseogliflozin group n = 302, placebo group n = 191). The primary outcomes were changes in fatty liver index (FLI) and Hepamet fibrosis score (HFS) after 24 weeks. The secondary outcomes were changes in cardiometabolic risk factors after 24 weeks. Statistical analysis was performed using propensity scoring analysis by the inverse probability of treatment weighting method.ResultsPrimary outcomes: Luseogliflozin significantly decreased FLI compared to placebo after 24 weeks (adjusted coefficient − 5.423, 95%CI − 8.760 to − 2.086, P = 0.0016). There was no significant difference in changes in HFS between the two groups. However, luseogliflozin significantly decreased HFS compared to placebo in diabetic patients with ALT > 30 U/L (adjusted coefficient − 0.039, 95%CI − 0.077 to − 0.001, P = 0.0438) and with FIB-4 index > 1.3 (adjusted coefficient − 0.0453, 95%CI − 0.075 to − 0.016, P = 0.0026). Secondary outcom8es: Luseogliflozin significantly decreased HbA1c level, HOMA-IR value, BMI, and uric acids level, and increased HDL cholesterol level compared to placebo.ConclusionsThis pooled meta-analysis demonstrated that 24-week treatment with luseogliflozin improved hepatic steatosis and fibrosis indexes in diabetic patients, especially those with liver injury. Furthermore, luseogliflozin improved various cardiometabolic risk factors. Thus, luseogliflozin may be useful for improving MASLD in diabetic patients.Graphical abstract

01 Sep 2024·Kidney International

Evaluation of glomerular hemodynamic changes by sodium-glucose-transporter 2 inhibition in type 2 diabetic rats using in vivo imaging

Article

Author: Wada, Yoshihisa ; Cherney, David Z I ; Kanda, Eiichiro ; Tokuyama, Atsuyuki ; Kadoya, Hiroyuki ; Sasaki, Tamaki ; Kondo, Megumi ; Nagasu, Hajime ; Kashihara, Naoki ; Kidokoro, Kengo

The mechanisms responsible for glomerular hemodynamic regulation with sodium-glucose co-transporter 2 (SGLT2) inhibitors in kidney disease due to type 2 diabetes remain unclear. Therefore, we investigated changes in glomerular hemodynamic function using an animal model of type 2 diabetes, treated with an SGLT2 inhibitor alone or in combination with a renin-angiotensin-aldosterone system inhibitor using male Zucker lean (ZL) and Zucker diabetic fatty (ZDF) rats. Afferent and efferent arteriolar diameter and single-nephron glomerular filtration rate (SNGFR) were evaluated in ZDF rats measured at 0, 30, 60, 90, and 120 minutes after the administration of a SGLT2 inhibitor (luseogliflozin). Additionally, we assessed these changes under the administration of the adenosine A1 receptor (A1aR) antagonist (8-cyclopentyl-1,3-dipropylxanthine), along with coadministration of luseogliflozin and an angiotensin II receptor blocker (ARB), telmisartan. ZDF rats had significantly increased SNGFR, and afferent and efferent arteriolar diameters compared to ZL rats, indicating glomerular hyperfiltration. Administration of luseogliflozin significantly reduced afferent vasodilatation and glomerular hyperfiltration, with no impact on efferent arteriolar diameter. Urinary adenosine levels were increased significantly in the SGLT2 inhibitor group compared to the vehicle group. A1aR antagonism blocked the effect of luseogliflozin on kidney function. Co-administration of the SGLT2 inhibitor and ARB decreased the abnormal expansion of glomerular afferent arterioles, whereas the efferent arteriolar diameter was not affected. Thus, regulation of afferent arteriolar vascular tone via the A1aR pathway is associated with glomerular hyperfiltration in type 2 diabetic kidney disease.

01 Jul 2024·Diabetes

The Early Pathogenesis of Diabetic Retinopathy and Its Attenuation by Sodium–Glucose Transporter 2 Inhibitors

Article

Author: Yamada, Ken-ichi ; Yamato, Mayumi ; Kato, Nao ; Inoguchi, Toyoshi

The early pathogenetic mechanism of diabetic retinopathy (DR) and its treatment remain unclear. Therefore, we used streptozotocin-induced diabetic mice to investigate the early pathogenic alterations in DR and the protective effect of sodium–glucose cotransporter 2 (SGLT2) inhibitors against these alterations. Retinal vascular leakage was assessed by dextran fluorescence angiography. Retinal thickness and vascular leakage were increased 2 and 4 weeks after onset of diabetes, respectively. Immunostaining showed that morphological change of microglia (amoeboid form) was observed at 2 weeks. Subsequently, increased angiopoietin-2 expression, simultaneous loss of pericytes and endothelial cells, decreased vessel density, retinal hypoxia, and increased vascular endothelial growth factor (VEGF)-A/VEGF receptor system occurred at 4 weeks. SGLT2 inhibitors (luseogliflozin and ipragliflozin) had a significant protective effect on retinal vascular leakage and retinal thickness at a low dose that did not show glucose-lowering effects. Furthermore, both inhibitors at this dose attenuated microglia morphological changes and these early pathogenic alterations in DR. In vitro study showed both inhibitors attenuated the lipopolysaccharide-induced activation of primary microglia, along with morphological changes toward an inactive form, suggesting the direct inhibitory effect of SGLT2 inhibitors on microglia. In summary, SGLT2 inhibitors may directly prevent early pathogenic mechanisms, thereby potentially playing a role in preventing DR.Article Highlights

100 Deals associated with Luseogliflozin Hydrate

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External Link

KEGG	Wiki	ATC	Drug Bank
D10195	Luseogliflozin Hydrate	A10BH	DB12214

R&D Status

10 top approved records.

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

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


JPRN-jRCTs011180019 \| JPRN-UMIN000031451 (EASD2021)	Phase 4	Diabetes Mellitus, Type 2 \| Hypertension	56	Luseogliflozin 2.5 mg/day	pttmixtrip(yktbngyqml) = xucualodzt anezdwkbnd (xzzdzifctn )	Positive	30 Sep 2021
				DPP-4i	pttmixtrip(yktbngyqml) = tjqdvgciqj anezdwkbnd (xzzdzifctn ) View more
EASD2020	Not Applicable	Insulinoma	-	Luseogliflozin 0.01%	zxoejfvmxu(gqdcqpuufa) = musmwsxadn mbxvrvwnnf (lmdvhtdmpv ) View more	-	22 Sep 2020
				Luseogliflozin	kzjusekzvv(sxtmuxfgul) = zxazdobcdv krrerwnpou (mxuhlnlawo )
ASN2019	Phase 3	Diabetes Mellitus, Type 2	941	Luseogliflozin 2.5 mg daily	(ipwntpfifz) = mmzbkylyub wwbavfftwj (kyetegxbxy )	Positive	05 Nov 2019
ISC2018	Not Applicable	Hyperglycemia	-	Luseogliflozin 2.5mg	kjspftynol(gzfrczlteq) = piwvpsiesr eysgcibrjv (azhzfebjmo )	-	22 Jan 2018
EASD2016	Not Applicable	Insulinoma	6	Luseogliflozin	zypcdfddcm(znsyxivxrv) = elevated relative to Controls ktqnpxsfyv (pzrzoftrhp ) View more	Positive	13 Sep 2016
				luseogliflozin
EASD2015	Not Applicable	Fatty Liver	16	Luseogliflozin	(fotzzuiegk) = inmgxfrlce znlcgqmwxh (qqhukuvymg, 58.8 - 76.2) View more	Positive	17 Sep 2015
				Sitagliptin	(fotzzuiegk) = wymuyqzhml znlcgqmwxh (qqhukuvymg, 59.6 - 76.3) View more
JPRN-JapicCTI-111507 (EASD2013)	Not Applicable	Diabetes Mellitus, Type 2 Add-on	221	Luseogliflozin 2.5 mg	(ibigiydlrj) = Incidence of hypoglycemia with patients who received luseogliflozin for 52 weeks was 10.7% and there were no major hypoglycemia or hypoglycemia leading to discontinuation. The incidences of urinary tract infection/genital infection and pollakiuria were 2.7% and 2.8%, and every event was mild in severity. pdfnqpjtud (ikxjnrhyhm )	Positive	26 Sep 2013
JPRN-JapicCTI-111508 (EASD2013)	Phase 3	Diabetes Mellitus, Type 2 Add-on	487	Luseogliflozin 2.5 mg	adxcsxeomx(hksxailiiv) = observed in all groups, but most of these events were mild in severity tjjqcxfvdg (zukozktshy ) View more	Positive	25 Sep 2013
				Luseogliflozin 5 mg
JPRN-JapicCTI-111661 \| JPRN-JapicCTI-111509 (EASD2013)	Phase 3	Diabetes Mellitus, Type 2	-	Luseogliflozin 2.5 mg	(lzcubkokra) = Frequencies of adverse events were similar across groups (Luseogliflozin 2.5mg, 59.5%; placebo, 57.0%) in Study-1 and 75.3% in Study-2. Most adverse events were mild in severity. There were no major changes in clinical laboratory tests. Luseogliflozin was well tolerated throughout both studies. obickoislt (cpugbcrrwp )	Positive	25 Sep 2013