Suglat (ipragliflozin) / Kotobuki, Astellas, Merck (MSD) - LARVOL DELTA

Effect of SGLT-2 inhibitors on liver fibrosis progression in patients with MASLD: an updated meta-analysis based on RCTs. (PubMed, Front Med (Lausanne)) - "Subgroup analyses indicated that empagliflozin and ipragliflozin may be more efficacious, with their benefits more pronounced in patients receiving short-term treatment (<24 weeks) and those with combined T2DM. SGLT-2 inhibitors may delay the progression of liver fibrosis in patients with MASLD, particularly by improving serologic parameters. However, additional high-quality studies are needed to validate their clinical value."

Journal • Retrospective data • Review • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Type 2 Diabetes Mellitus

Comparison of the efficacy of antidiabetic agents in type 2 diabetes with MASLD: a network meta-analysis. (PubMed, Front Endocrinol (Lausanne)) - "Ertugliflozin was the most effective in reducing ALT and AST levels, followed by pioglitazone and metformin for ALT, and pioglitazone and ipragliflozin for AST. Ertugliflozin may be the most effective option for improving liver function and metabolic parameters in patients with MASLD and T2DM. Further studies are needed to confirm these findings."

Clinical • Journal • Retrospective data • Review • Diabetes • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Type 2 Diabetes Mellitus

Evaluating the Comparative Effectiveness of Sodium-Glucose Transporter 2 Inhibitors (SGLT-2i) on Liver Enzymes in Patients With Nonalcoholic Fatty Liver Disease: A Comprehensive Systematic Review and Bayesian Network Meta-Analysis of Randomized Controlled Trials. (PubMed, AACE Endocrinol Diabetes) - "Empagliflozin topped fibrosis-4 score reduction (MD: -0.12, 95% CrI: -0.42 to 0.13, SUCRA: 73.27%). SGLT-2 inhibitors significantly improve liver and metabolic outcomes in NAFLD, with dapagliflozin, ipragliflozin, and empagliflozin offering distinct benefits, supporting personalized treatment strategies."

HEOR • Journal • Retrospective data • Review • Diabetes • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Type 2 Diabetes Mellitus

Drug Development. (PubMed, Alzheimers Dement) - "These findings enhance understanding of LD formation and isoform-specific differences in astrocytes. Given the role of LDs in AD, these insights may contribute to understanding AD pathogenesis and identifying therapeutic strategies."

Journal • APOE • PLIN2

Effect of Oral Hypoglycaemic Agents on Carotid Artery Intima-Media Thickness in Patients With Cardiovascular Disease and/or Diabetes-A Systematic Review. (PubMed, Endocrinol Diabetes Metab) - "The study suggests that prolonged use of Pioglitazone, Repaglinide and Alogliptin may significantly slow CIMT progression, improving cardiovascular risk management in patients with diabetes and/or cardiovascular disease. Further research is needed to understand the benefits and optimise oral hypoglycaemic treatment strategies for these patients."

Journal • Review • Atherosclerosis • Cardiovascular • Diabetes • Hypoglycemia • Inflammation • Metabolic Disorders • Type 1 Diabetes Mellitus

Diabetic Ketoacidosis and Severe Hypoglycemia Risks with Ipragliflozin/Insulin Versus Insulin in Type 1 Diabetes: A Japanese Real-World Database Study. (PubMed, Diabetes Ther) - "Ipragliflozin/insulin combination therapy showed no difference in the incidence of DKA, but a lower incidence of SH, versus insulin therapy in patients with T1D in Japan. These results suggest that ipragliflozin treatment is not associated with increased incidences of initial DKA or SH; however, its use should be accompanied by appropriate monitoring, education, and risk mitigation strategies to minimize the occurrence of these events."

Journal • Real-world evidence • Diabetes • Hypoglycemia • Metabolic Disorders • Severe Hypoglycemia • Type 1 Diabetes Mellitus

A Meta-Analysis of Type 2 Diabetes Mellitus Treatments for MASLD (ACG 2025) - "Heterogeneity of fibrosis data was low with I2 of 0% and significant fixed and random effects models (p < 0.001). Out of the seven trials only Takahashi et al. (ipragliflozin) and Loomba et al."

Retrospective data • Diabetes • Fibrosis • Genetic Disorders • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • Type 2 Diabetes Mellitus

Limited Approvals in MASLD Highlight the Need to Reevaluate FDA Guidance for Outcome Measures (ACG 2025) - "SGLT-2 inhibitor, Ipragliflozin demonstrated significant improvement in fibrosis (OR 7; 95% CI 1.77-27.68), however it's effect on steatohepatitis was not reported. While GLP-1 receptor agonist (GLP-1 RA) Liraglutide had significant impact of steatohepatitis resolution (OR 6.43; 95% CI 1.20-34.41) in a phase 2 trial without a follow up phase 3 study...Obeticholic acid did show improvement in fibrosis (OR 2.22; 95% CI 1.44-3.42), but did not receive FDA approval due to its risk-benefit profile. Resmetirom is currently the only FDA-approved therapy for MASLD... Of the 464 RCTs identified, only 63 were assessing pharmacotherapies. Despite these drugs demonstrating meaningful improvement through non-invasive assessments such as FibroScan and MRI-PDFF, over 75% of these studies were not eligible for FDA approval pathways, given the current regulatory requirement of biopsy-based endpoints. Only 10 of the 63 studies were evaluating liver biopsy based on steatohepatitis..."

Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease

SGLT-2 inhibitors beyond diabetes: A new frontier in cancer treatment. (PubMed, Diabetes Res Clin Pract) - "Sodium-glucose co-transporter 2 (SGLT-2) inhibitors, a new class of antidiabetic medications including canagliflozin, dapagliflozin, ipragliflozin, and empagliflozin, recently came to light as possible anti-cancer therapeutics. They seem to regulate a diverse array of intracellular and extracellular signaling pathways, encompassing those associated with microRNAs, AMPK, ERK, DNA and RNA metabolism, ATP homeostasis, and mitochondrial function. These data collectively underscore the potential of SGLT-2 inhibitors in clinical oncology and elucidate the processes driving their anti-cancer efficacy."

Journal • Review • Cardiovascular • Congestive Heart Failure • Diabetes • Heart Failure • Metabolic Disorders • Oncology • AMPK

Comparative efficacy of sodium-glucose transporter 2 inhibitors on lipid profiles in nonalcoholic fatty liver disease (NAFLD): a comprehensive Bayesian network meta-analysis. (PubMed, Ann Med Surg (Lond)) - "Empagliflozin and ipragliflozin demonstrated superior efficacy in improving lipid profiles, while dapagliflozin was most effective for BMI reduction in NAFLD patients. These findings align with their cardiovascular and metabolic benefits, offering a multifaceted approach to a complex disease. Further research is needed to confirm long-term effects and optimize treatment strategies for diverse NAFLD populations."

Journal • Retrospective data • Cardiovascular • Diabetes • Dyslipidemia • Genetic Disorders • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • Type 2 Diabetes Mellitus

Evaluation of three mechanisms of action (SGLT2 inhibitors, GLP-1 receptor agonists, and sulfonylureas) in treating type 2 diabetes with heart failure: a systematic review and network meta-analysis of RCTs. (PubMed, Front Endocrinol (Lausanne)) - "A Bayesian network meta-analysis was utilized to integrate direct and indirect evidence, facilitating a comparative ranking of various SGLT2 inhibitors-canagliflozin (CANA), ipragliflozin (IPRA), empagliflozin (EMPA), remogliflozin (REMO), licogliflozin (LICO), and dapagliflozin (DAPA)-as well as one GLP-1 receptor agonist-semaglutide (SEMA)-and a sulfonylurea-glimepiride (GLIM)-with respect to their efficacy and safety profiles. Despite its moderate efficacy, GLIM remains a viable choice for certain patients due to its favorable safety profile and cost-effectiveness. Collectively, these findings provide essential evidence-based insights to guide individualized therapeutic strategies in type 2 diabetes complicated by heart failure."

Clinical • Journal • Retrospective data • Review • Cardiovascular • Congestive Heart Failure • Diabetes • Genetic Disorders • Heart Failure • Hypoglycemia • Infectious Disease • Metabolic Disorders • Nephrology • Obesity • Type 2 Diabetes Mellitus

Efficacy of Sodium-Glucose Cotransporter 2 Inhibitors in Patients With Type 2 Diabetes Mellitus and Nonalcoholic Fatty Liver Disease: A Systematic Review of Randomized Controlled Trials. (PubMed, Cureus) - "Included randomized controlled trials (RCTs) investigated various SGLT2 inhibitors, such as dapagliflozin, empagliflozin, ertugliflozin, and ipragliflozin. These findings suggest SGLT2 inhibitors may offer dual benefits for managing both diabetes and fatty liver disease. Further long-term studies focusing on liver histology as a primary endpoint are needed to confirm these effects."

Journal • Review • Cardiovascular • Diabetes • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Type 2 Diabetes Mellitus

Adjunct Therapy with Ipragliflozin Exerts Limited Effects on Kidney Protection in Type 1 Diabetes: A Retrospective Study Conducted at 25 Centers in Japan (IPRA-CKD). (PubMed, Biomedicines) - " Adjunctive treatment with ipragliflozin exerted potential renal benefits by decreasing proteinuria in T1D subjects with CKD. Further investigations are required to determine whether its additional benefits exceed the increased risk of ketoacidosis."

Journal • Retrospective data • Cardiovascular • Chronic Kidney Disease • Diabetes • Metabolic Disorders • Nephrology • Renal Disease • Severe Hypoglycemia • Type 1 Diabetes Mellitus • Type 2 Diabetes Mellitus

Comparative efficacy and safety of SGLT2 inhibitor class members in patients with heart failure and type 2 diabetes: A systematic review and network meta-analysis of randomized controlled trials. (PubMed, Diabetes Res Clin Pract) - "Arms included canagliflozin (n = 2), dapagliflozin (n = 6), empagliflozin (n = 6), ertugliflozin (n = 1), ipragliflozin (n = 1), sotagliflozin (n = 1), placebo (n = 13), and standard of care (n = 4). In patients with HF and T2DM, SGLT2i class effects include ACM, ACH, and HHF reduction. Among SGLT2i, canagliflozin showed greatest ACM, CVD, and HHF benefit."

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

Impact of baseline left ventricular ejection fraction and body mass index on the effect of 24-week Ipragliflozin treatment on left ventricular diastolic function in patients with type 2 diabetes and chronic kidney disease: insights from the PROCEED trial. (PubMed, Cardiovasc Diabetol) - "In subgroups with higher LVEF and BMI, ipragliflozin improved diastolic function more than standard treatment. These results may partly support the beneficial effect of SGLT2 inhibitors on LV diastolic performance."

Journal • Chronic Kidney Disease • Diabetes • Metabolic Disorders • Nephrology • Renal Disease • Type 2 Diabetes Mellitus

Development of a Concise Synthetic Approach to Gliflozin Aglycones from Regioselective Deprotonation of 1,4-Dihalobenzenes. (PubMed, J Org Chem) - "Herein, we report a concise synthetic approach to gliflozin (SGLT2 inhibitors) aglycones from generating regioselective ortho-lithiation based on differentiating the acidifying effect of 1,4-dihalobenzenes and reacting with (hetero)aromatic aldehydes. Then, the resulting diarylmethyl alcohol was converted to diarylmethane using acid-mediated reduction, offering a two-step practical method for synthesizing aglycones of various gliflozins such as Dapagliflozin, Empagliflozin, and Ipragliflozins."

Journal

Exploring SGLT2 Inhibitors' Activity in Breast Cancer: An Overview. (PubMed, Curr Top Med Chem) - "The effects of four different SGLT2 inhibitors on breast cancer cells were investigated in this study via both in vitro and in vivo testing: dapagliflozin, ipragliflozin, canagliflozin, and empagliflozin. Additionally, this study highlights how SGLT2 inhibitors may be used in conjunction with precision medicine techniques to treat breast cancer. Although encouraging outcomes have been noted, this review highlights the necessity of additional clinical studies to evaluate the safety and effectiveness of SGLT2 blockers in patients with breast cancer, in addition to ongoing research into the molecular mechanisms underlying the anticancer effects of these drugs."

Journal • Breast Cancer • Diabetes • Metabolic Disorders • Oncology • Solid Tumor

Physiologically based pharmacokinetic model of sodium-glucose cotransporter 2 inhibitors predicted pharmacokinetics and pharmacodynamics to explore dosage regimen for patients with type 2 diabetes mellitus and renal insufficiency. (PubMed, Front Pharmacol) - "It was predicted that optimal hypoglycemic effects would be achieved in T2DM patients with mild, moderate, and severe renal insufficiency, when treated with ipragliflozin 50 mg qd, dapagliflozin 10 mg qd or canagliflozin 100 mg qd, empagliflozin 10 mg, respectively. This study provided a scientific basis for optimizing the dosage regimen in T2DM patients with renal insufficiency."

Journal • PK/PD data • Diabetes • Metabolic Disorders • Nephrology • Renal Disease • Type 2 Diabetes Mellitus

Efficacy and safety of 11 sodium-glucose cotransporter-2 inhibitors at different dosages in type 2 diabetes mellitus patients inadequately controlled with metformin: a Bayesian network meta-analysis. (PubMed, BMJ Open) - "As add-on therapy, SGLT2is demonstrated favourable antidiabetic efficacy and acceptable safety. 300 mg of canagliflozin was the best option among the included interventions considering favourable glucose control and WL. Some novel SGLT2is (eg, henagliflozin) exhibited promising efficacy and safety profiles, but more research is needed to validate the findings."

Clinical • Journal • Retrospective data • Review • Diabetes • Hypoglycemia • Infectious Disease • Metabolic Disorders • Nephrology • Type 2 Diabetes Mellitus

Hypouricemic effect of sodium glucose transporter-2 inhibitors: a network meta-analysis and meta-regression of randomized clinical trials. (PubMed, Expert Rev Endocrinol Metab) - "Specific reductions were noted for ertugliflozin (-42.17 μmol/L), dapagliflozin (-40.28 μmol/L), empagliflozin (-46.75 μmol/L), canagliflozin (-35.55 μmol/L), and ipragliflozin (-10.48 μmol/L). These findings suggest a potential role in reducing cardiovascular risk. Further research is needed to explore their effects on hyperuricemic patients, and monitoring serum uric acid levels is recommended."

Clinical • Journal • Retrospective data • Review • Cardiovascular

Effects of the SGLT2 inhibitor ipragliflozin and metformin on hepatic steatosis and liver fibrosis: Sub-analysis of a randomized controlled study. (PubMed, Diabetes Obes Metab) - "Compared with metformin, ipragliflozin improved multiple hepatic steatosis and liver fibrosis indices, suggesting that ipragliflozin exerts potential hepatoprotective effects in early-stage liver disease associated with T2D."

Journal • Addiction (Opioid and Alcohol) • Diabetes • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Type 2 Diabetes Mellitus

Effect of the SGLT2 inhibitor ipragliflozin on the expression of genes that regulate skin function. (PubMed, Diabet Med) - "It was revealed that ipragliflozin reduces the expression of genes involved in skin barrier and moisturizing functions, which this may be one of the mechanisms through which this drug causes skin disorders."

Journal • Dermatology • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus • ASAH1 • COL1A1 • COL1A2 • FLG • LORICRIN

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

A Study to Assess the Safety and Tolerability of ASP1941 in Adults With Type 2 Diabetes Mellitus. (clinicaltrials.gov) - P2 | N=61 | Completed | Sponsor: Astellas Pharma Inc | Phase classification: P2a ➔ P2

Phase classification • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus