Lusefi (luseogliflozin) / Taisho - LARVOL DELTA

Letter to the Editor in response to the article "Effect of luseogliflozin on liver fibrosis differs depending on alcohol consumption in patients with type 2 diabetes". (PubMed, J Diabetes Investig) - No abstract available

Journal • Diabetes • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Metabolic Disorders • Type 2 Diabetes Mellitus

Clinical efficacy and safety of sodium-glucose cotransporter protein-2 (SGLT-2) inhibitor, glucagon-like peptide-1 (GLP-1) receptor agonist, and Finerenone in type 2 diabetes mellitus with non-dialysis chronic kidney disease: a network meta-analysis of randomized clinical trials. (PubMed, Front Pharmacol) - "According to the SUCRA based relative ranking of treatments, Empagliflozin was the most effective in reducing HbA1c and DBP...Liraglutide was the most effective in reducing LDL-C. Bexagliflozin, Canagliflozin were the most effective in reducing SBP and body weight. Finerenone had the lowest incidence of urinary tract infection, Hypoglycemia was the lowest in the Luseogliflozin group. Ertugliflozin was the least likely to cause acute kidney injury...SGLT-2 inhibitors had a preferential glucose-lowering and weight-loss function, GLP-1 receptor agonists had a preferential lowering of LDL-C and blood glucose, and Finereone significantly reduced SBP compared with PBO. Systematic Review Registration: PROSPERO, CRD42024571544."

Clinical • Journal • Retrospective data • Review • Acute Kidney Injury • Chronic Kidney Disease • Diabetes • Diabetic Nephropathy • Dyslipidemia • Hypoglycemia • Infectious Disease • Metabolic Disorders • Nephrology • Renal Disease • Type 2 Diabetes Mellitus

VASCULAR PROTECTIVE EFFECTS OF SGLT2 INHIBITION IN AD/ADRD (ADPD 2025) - " TgF344-AD rats were orally admin istered luseogliflozin (20 mg/kg/day) for 3 months... These findings suggest that SGLT2 inhibition is a promising therapeutic approach for addressing vascular dysfunction in AD."

Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Diabetes • Metabolic Disorders

Effect of luseogliflozin on liver fibrosis differs depending on alcohol consumption in patients with type 2 diabetes. (PubMed, J Diabetes Investig) - "HbA1c levels and body weight decreased in patients with type 2 diabetes after initiating luseogliflozin therapy, regardless of drinking habits. However, it is desirable to limit alcohol consumption when considering its effects on liver fibrosis."

Journal • Diabetes • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Metabolic Disorders • Type 2 Diabetes Mellitus

Luseogliflozin Persistently Lowers Glycemia and Body Weight Over a Period of Two Years in Patients With Type 2 Diabetes. (PubMed, Cureus) - "The effects of luseogliflozin on glucose and BW reduction were sustained for at least two years, indicating similarity to other SGLT2 inhibitors."

Journal • Cardiovascular • Congestive Heart Failure • Diabetes • Heart Failure • Metabolic Disorders • Type 2 Diabetes Mellitus

Ranibizumab with luseogliflozin in type 2 diabetes with diabetic macular oedema: A randomised clinical trial. (PubMed, Diabetes Obes Metab) - "Although the overall number of anti-VEGF injections in the target eye showed no significant difference, some patients responded favourably to SGLT2i and required fewer injections. The reduction in fellow eye injections suggests SGLT2i's efficacy in treating early-stage DMO."

Journal • Diabetes • Diabetic Macular Edema • Diabetic Retinopathy • Macular Edema • Metabolic Disorders • Ophthalmology • Retinal Disorders • Type 2 Diabetes Mellitus

Long-term renoprotective effect of luseogliflozin in type 2 diabetes patients: CHikushi Anti-diabetes mellitus Trial-Lusefi (CHAT-Lu). (PubMed, Drug Discov Ther) - "There were four adverse events, but no serious adverse events closely related to luseogliflozin treatment. In type 2 diabetes patients, 2-year treatment with luseogliflozin provided beneficial metabolic effects and improved the rate of decline in eGFR, suggesting a renal protective effect."

Journal • Observational data • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Expanding access to sodium-glucose cotransporter 2 inhibitors (SGLT2i) in the Ministry of Health Malaysia - a multiple HTA approach. (PubMed, Int J Technol Assess Health Care) - "The multiple HTA approach guided the complex decision-making process by providing a holistic understanding of the decision's impact."

Journal • Review • Cardiovascular

A retrospective study of seasonal variation in sodium-glucose co-transporter 2 inhibitor-related adverse events using the Japanese adverse drug event report database. (PubMed, Sci Rep) - "Six SGLT2 inhibitors prescribed in Japan (ipragliflozin, empagliflozin, luseogliflozin, canagliflozin, dapagliflozin, and tofogliflozin) were included. Healthcare providers should take adequate precautions against dehydration caused by SGLT2 inhibitors, not only in summer but also in winter. These findings are instructive and informational for health care professionals involved in diabetes care."

Adverse events • Journal • Retrospective data • CNS Disorders • Diabetes • Infectious Disease • Metabolic Disorders • Nephrology • Type 2 Diabetes Mellitus

Model-based meta-analysis of HbA1c reduction across SGLT2 inhibitors using dose adjusted by urinary glucose excretion. (PubMed, Sci Rep) - "This study was aimed to evaluate whether the dose-response relationship of the sodium glucose co-transporter-2 inhibitors (SGLT2is) in patients with type 2 diabetes mellitus (T2DM)-canagliflozin, dapagliflozin, empagliflozin, ipragliflozin, luseogliflozin, and tofogliflozin-can be explained in a unified manner based on their ability to promote urinary glucose excretion (UGE). Findings from this study would influence drug selection and adjustment in clinical practice. As with SGLT2is, in cases where the efficacy cannot be easily evaluated but an appropriate pharmacodynamic marker was assessed in early clinical trials, similar approaches for other drug classes can guide strategic and evidence-based dose selection in phase III trials."

Clinical • Journal • Retrospective data • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Telogen Effluvium Following the Treatment of Euglycemic Diabetic Ketoacidosis in a Patient With Heavy Soft Drink Intake: A Case Report. (PubMed, Cureus) - "This case report discusses a man with type 2 diabetes mellitus associated with heavy soft drink intake who developed telogen effluvium following treatment for euglycemic diabetic ketoacidosis with luseogliflozin...Physical wasting due to hyperglycemia and ketoacidosis was assumed to have triggered hair loss, resulting in rapid weight loss. Investigating the triggers associated with alopecia is crucial for diagnosing and treating telogen effluvium."

Journal • Alopecia • Diabetes • Immunology • Metabolic Disorders • Type 2 Diabetes Mellitus

Comparison of protective effects of teneligliptin and luseogliflozin on pancreatic β-cell function: randomized, parallel-group, multicenter, open-label study (SECRETE-I study). (PubMed, Front Endocrinol (Lausanne)) - "On the other hand, it is likely that alleviation of β-cell dysfunction is more effective with luseogliflozin compared to tenegliptin. https://rctportal.niph.go.jp/en, identifier jRCTs061190008."

Clinical • Journal • Diabetes • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

SGLT2 Inhibitors Reduce the Progression from AKI to CKD by Inhibiting Ferroptosis (KIDNEY WEEK 2024) - "Luseogliflozin mitigates the progression from AKI to CKD by modulating metabolic pathways and reducing oxidative stress and ferroptosis. This study suggests a potential therapeutic role for SGLT2 inhibitors in the management of AKI, advocating for further clinical investigation."

Acute Kidney Injury • Chronic Kidney Disease • Diabetes • Diabetic Nephropathy • Fibrosis • Immunology • Inflammation • Metabolic Disorders • Nephrology • Reperfusion Injury • AMPK

EFFECTS OF LUSEOGLIFLOZIN ON MASLD IN PATIENTS WITH TYPE 2 DIABETES MELLITUS: A POOLED META-ANALYSIS OF PHASE III CLINICAL TRIALS (AASLD 2024) - "This 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 as well as liver function tests. Thus, luseogliflozin may be useful for improving MASLD in diabetic patients."

P3 data • Retrospective data • Diabetes • Fibrosis • Hepatology • Immunology • Liver Failure • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Type 2 Diabetes Mellitus

Comparison of kidney and hepatic outcomes among sodium-glucose cotransporter-2 inhibitors: a retrospective study using multiple propensity scores. (PubMed, J Pharm Health Care Sci) - "Renoprotective and hepatoprotective effects are class effects of SGLT2i, and their effects are thought to be independent of kidney or liver status."

Journal • Retrospective data • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Diabetes • Dyslipidemia • Heart Failure • Metabolic Disorders • Nephrology • Renal Disease

SGLT2 inhibition mitigates transition from acute kidney injury to chronic kidney disease by suppressing ferroptosis. (PubMed, Sci Rep) - "Immunostaining showed reduced 4-hydroxynonenal and malondialdehyde levels, especially in renal tubules, indicating suppressed ferroptosis. Luseogliflozin may protect the kidney from I/R injury by inhibiting ferroptosis through oxidative stress reduction."

Journal • Acute Kidney Injury • Cardiovascular • Chronic Kidney Disease • Fibrosis • Immunology • Nephrology • Renal Disease • Reperfusion Injury • GPX4 • SIRT3 • TFRC

A Randomized Controlled Trial on the Effect of Luseogliflozin on Bone Microarchitecture Evaluated Using HR-pQCT in Elderly Type 2 Diabetes. (PubMed, Diabetes Ther) - "In the pilot trial, we observed no negative effect of 48-week luseogliflozin treatment on bone microarchitecture or bone strength in elderly people with T2D."

Journal • Cardiovascular • Diabetes • Metabolic Disorders • Musculoskeletal Diseases • Orthopedics • Osteoporosis • Rheumatology • Type 2 Diabetes Mellitus

Effects of luseogliflozin on suspected MASLD in patients with diabetes: a pooled meta-analysis of phase III clinical trials. (PubMed, J Gastroenterol) - "This 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."

Journal • P3 data • Retrospective data • Diabetes • Fibrosis • Hepatology • Immunology • Liver Failure • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease

Preadministration of SGLT2 Inhibitor Reduces Frequency of Anti-VEGF Agent Administration in Patients with Mild Diabetic Macular Edema—A Multicenter Randomized Controlled Open-Label Trial (ADA 2024) - "However, no interventional studies have been conducted. Sixty patients with DME were enrolled and divided into an SGLT2i group (SG) treated with luseogliflozin and a control group treated with glimepiride. The pre-administration of SGLT2i reduced the frequency of anti-VEGF agent administration for mild DME."

Clinical • Metabolic Disorders

Efficacy and safety of luseogliflozin in patients with type 2 diabetes mellitus: a systematic review and meta-analysis. (PubMed, Endocrine) - "The current study identified a significant improvement in efficacy outcomes of HbA1c, FPG, PPG, and body weight in the luseogliflozin group. Non-significant safety results may be due to a smaller population size and fewer studies. Hence, long-term multicentric RCTs are needed to identify the safety and efficacy in a diversified population."

Journal • Retrospective data • Review • Diabetes • Hypoglycemia • Metabolic Disorders • Type 2 Diabetes Mellitus

Effects of Switching From Another Sodium-Glucose Cotransporter 2 Inhibitor to Tofogliflozin on Nocturia in Patients With Type 2 Diabetes. (PubMed, Cureus) - "The switch from another SGLT2 inhibitor to tofogliflozin may reduce the frequency of nocturnal urination, implying that it may have a positive impact on the quality of life of patients with type 2 diabetes."

Journal • Diabetes • Genito-urinary Cancer • Metabolic Disorders • Oncology • Prostate Cancer • Solid Tumor • Type 2 Diabetes Mellitus

Evaluation of glomerular hemodynamic changes by sodium-glucose-transporter 2 inhibition in type 2 diabetic rats using in vivo imaging. (PubMed, Kidney Int) - "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. 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."

Journal • Preclinical • Diabetes • Diabetic Nephropathy • Metabolic Disorders • Nephrology • Renal Disease • Type 2 Diabetes Mellitus • NGFR

Effect of Luseogliflozin, a Sodium-Glucose Cotransporter 2 Inhibitor, and Dipeptidyl-Peptidase 4 Inhibitors on the Quality-of-Life and Treatment Satisfaction of Patients With Type 2 Diabetes Mellitus: A Subanalysis of a Multicenter, Open-Label, Randomized-Controlled Trial (J-SELECT Study). (PubMed, Diabetes Ther) - "Physicians should pay attention to side effects of SGLT2is to maintain the patients' QOL when SGLT2is are initiated or added-on. Add-on of luseogliflozin increased patients' QOL more than DPP-4is. Considering patients' QOL and treatment satisfaction is important for selecting SGLT2is or DPP-4is."

HEOR • Journal • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

The Early Pathogenesis of Diabetic Retinopathy and Its Attenuation by Sodium-Glucose Transporter 2 Inhibitors. (PubMed, Diabetes) - "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. In vitro study, 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, SGLT2i may directly prevent early pathogenic mechanisms, thereby potentially playing a role in preventing DR."

Journal • Diabetes • Diabetic Retinopathy • Metabolic Disorders • Retinal Disorders • ANGPT2

Effect of Luseogliflozin on Myocardial Flow Reserve in Patients with Type 2 Diabetes Mellitus (LUCENT-J Study). (PubMed, Diabetes Ther) - "The LUCENT-J study will elucidate the mechanisms of cardioprotection by SGLT2 inhibitors in patients with T2D. Japan Registry of Clinical Trials (JRCTs051220016)."

Journal • Cardiovascular • Congestive Heart Failure • Coronary Artery Disease • Diabetes • Heart Failure • Metabolic Disorders • Myocardial Infarction • Type 2 Diabetes Mellitus