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

SGLT2 Inhibitor, Ipragliflozin, Suglat, Effect on Lipid and Glucose Metabolism Study (clinicaltrials.gov) - P4 | N=200 | Completed | Sponsor: Fukujuji Hospital, Japan Anti-Tuberculosis Association | Unknown status ➔ Completed

Trial completion • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus • LEP

Favorable CGM metrics do not exclude SGLT2 inhibitor-associated euglycemic diabetic ketoacidosis: an educational case report with narrative review of literature. (PubMed, Endocr J) - "We report an educational case of a 45-year-old man with type 1 diabetes (T1D) receiving ipragliflozin who developed severe euDKA precipitated by COVID-19...Therefore, clinicians must prioritize symptom-based sick-day rules over "normal" glucose numbers to prevent false reassurance from clinically acceptable CGM metrics. This case underscores the inherent limitations of glucose-centric monitoring and the necessity of multifaceted patient education."

Journal • Diabetes • Infectious Disease • Metabolic Disorders • Novel Coronavirus Disease • Type 1 Diabetes Mellitus

Association of Sodium-Glucose Cotransporter-2 Inhibitors With Fournier Gangrene: A Disproportionality Analysis Using the Japanese Adverse Drug Event Report Database. (PubMed, Am J Ther) - "All 5 SGLT2 inhibitors were associated with FG, with empagliflozin carrying the highest risk. Male patients exhibited elevated susceptibility. Continuous monitoring throughout treatment is essential. Further clinical trials are warranted to clarify causal relationships."

Adverse events • Journal • Genetic Disorders • Obesity

Fatty Liver Index and Differential Glycemic Responses to Ipragliflozin Versus Sitagliptin Over 52 Weeks: An Exploratory Post Hoc Analysis of the Niigata Ipragliflozin and Sitagliptin With Metformin (N-ISM) Study. (PubMed, Diabetes Obes Metab) - "FLI-based stratification was associated with differential glycemic responses to ipragliflozin versus sitagliptin. These findings are hypothesis-generating, given the small, complete-case sample and the sample-derived cut-off. Prospective studies are warranted before FLI can inform antidiabetic drug selection."

Journal • Retrospective data • Atherosclerosis • Cardiovascular • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Effects of SGLT2 inhibitors on body composition and potential sarcopenia-related outcomes in type 2 diabetes mellitus: a network meta-analysis. (PubMed, Front Endocrinol (Lausanne)) - "For LM, empagliflozin (mean difference [MD] -1.22 kg, 95% CI -1.71 to -0.72), ipragliflozin (MD -0.99 kg, 95% CI -1.45 to -0.54), and canagliflozin (MD -0.80 kg, 95% CI -1.39 to -0.21) were associated with modest reductions in LM compared with placebo, whereas dapagliflozin and tofogliflozin showed neutral effects. Findings for LM should be interpreted cautiously, as LM does not directly reflect muscle mass. https://www.crd.york.ac.uk/prospero/, identifier CRD420261379719."

Clinical • Journal • Retrospective data • Review • Cardiovascular • Diabetes • Metabolic Disorders • Obesity • Sarcopenia • Type 2 Diabetes Mellitus

Short-term sodium-glucose cotransporter 2 inhibition with ipragliflozin enhances engraftment and function in murine islet transplantation. (PubMed, Transpl Immunol) - "Early hepatic expression of inflammatory markers (tumor growth factor-β, interferon-γ, and interleukin-6) was lower in the Tx + Ip group, whereas expression of the islet survival gene Pdx1 was higher on day 5, suggesting enhanced islet engraftment. These findings indicate that short-term perioperative ipragliflozin improves islet transplantation outcomes in diabetic mice by attenuating early inflammation and supporting islet survival and function, with potential translational relevance for clinical islet transplantation strategies."

Journal • Preclinical • Diabetes • Metabolic Disorders • Oncology • Transplantation • IFNG • IL6 • PDX1

Pheochromocytoma unmasked by rapid deterioration of previously stable type 2 diabetes. (PubMed, JCEM Case Rep) - "A 46-year-old man with a 15-year history of type 2 diabetes had maintained hemoglobin A1c (HbA1c) around 6.5% (SI: 48 mmol/mol) (reference range, 4.7%-6.2% [28-44 mmol/mol]) for approximately 12 years on saxagliptin monotherapy, but glycemic control worsened over 1 year despite additional ipragliflozin and metformin. Antihypertensive and glucose-lowering medications were discontinued postoperatively, and glycemic control remained stable without antidiabetic medication at 6 months. This case highlights pheochromocytoma as a reversible endocrine cause of rapid worsening of previously stable type 2 diabetes."

Journal • Cardiovascular • Diabetes • Endocrine Cancer • Metabolic Disorders • Oncology • Pain • Solid Tumor • Type 2 Diabetes Mellitus

SAT-626 - Efficacy of SGLT2 Inhibitors in Reducing Hepatic Fibrosis in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis (ENDO 2026) - "SGLT2 inhibitors are associated with improved liver health in patients with T2DM and MASLD by improving metabolic profile, reducing inflammation, and attenuating fibrosis. Dapagliflozin, empagliflozin, and ipragliflozin showed the most consistent benefits. However, variability in FIB-4 and NFS results highlights the need for larger multicenter studies to confirm long-term efficacy and support broader clinical use."

Late-breaking abstract • Retrospective data • Review • Diabetes • Fibrosis • Hepatology • Immunology • Inflammation • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Type 2 Diabetes Mellitus

Palladium-Catalyzed Synthesis of S-Glycosides Via Stereoretentive Cross-Coupling. (PubMed, Org Lett) - "The reactivity and versatility of this reaction are demonstrated in over 30 examples, including different monosaccharides and disaccharides. Furthermore, the synthetic utility was highlighted by the synthesis of thiosugar analogues of ipragliflozin and dapagliflozin."

Journal

When Antidiabetic Therapy Affects the Skin – case report and literature review. (EADV-Sp 2026) - "Initial dermatological management included systemic antihistamines and topical triamcinolone combined with tetracycline spray...The patient was maintained on metformin monotherapy...This drug class includes canagliflozin, dapagliflozin, empagliflozin, ipragliflozin, luseogliflozin, and tofogliflozin [3]...Conclusions In the present case, blistering lesions developed after more than one year of empagliflozin therapy and showed partial remission following drug substitution and complete resolution after discontinuation of SGLT2 inhibitor treatment , suggesting a possible association with a non-autoimmune bullous reaction. This observation highlights the importance of considering SGLT2 inhibitors (flozins) in the in the differential diagnosis of bullous or blistering skin eruptions in patients with type 2 diabetes mellitus."

Case report • Clinical • Review • Bullous Pemphigoid • Cardiovascular • Dermatopathology • Diabetes • Hypotension • Immunology • Infectious Disease • Metabolic Disorders • Nephrology • Pruritus • Psoriasis • Type 2 Diabetes Mellitus

Effect of sodium-glucose cotransporter 2 inhibitors on heart failure readmission in older patients with diabetes: A Japanese claims-based cohort study. (PubMed, J Diabetes Investig) - "Among older patients with HF and diabetes, SGLT2i administration was associated with reduced HF readmission risk, with no meaningful differences among the four agents. These findings support a class-wide effect of SGLT2i and highlight the importance of their appropriate initiation and continuation in older adults."

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

Drug-Associated Ketoacidosis: A Comprehensive Disproportionality Analysis Based on the FAERS Database. (PubMed, Diabetes Obes Metab) - "The high-risk drugs for inducing ketoacidosis are mainly sodium-glucose cotransporter 2 (SGLT2) inhibitors (e.g., dapagliflozin and empagliflozin), followed by psychotropic drugs (e.g., quetiapine). Attention should also be paid to the potential risk of ketoacidosis induced by some drugs that do not mention this adverse reaction in their package inserts. The findings of this study can provide data support for clinical medication monitoring and the revision of drug package inserts."

Journal • Metabolic Disorders

Ipragliflozin Exerts Anti-Fibrotic Effects via a Novel Multi-Pathway Mechanism: Targeting TLR4/NF-κB /TGF-β1 Cascade. (PubMed, Int J Biochem Cell Biol) - "Histopathological and immunohistochemical findings confirmed a reduction in fibrosis and inflammation. These findings highlight Ipragliflozin's promise as a multi-faceted therapeutic agent for liver fibrosis."

Journal • Fibrosis • Immunology • Inflammation • Liver Cirrhosis • IL1B • TGFB1 • TLR4

Do SGLT2 Inhibitors Influence Parkinson’s Disease Risk? A Meta-analysis of Randomized Trials (AAN 2026) - "No eligible data were found for ertugliflozin, enavogliflozin, henagliflozin, ipragliflozin, luseogliflozin, or tofogliflozin...Subgroup analyses showed no significant effect for individual agents: empagliflozin 10 mg (OR 0.64, 95% CI 0.17–2.43), empagliflozin 25 mg (OR 0.33, 95% CI 0.01–8.15), dapagliflozin 10 mg (OR 0.33, 95% CI 0.09–1.23), sotagliflozin (OR 0.25, 95% CI 0.03–2.24), canagliflozin 100 mg (OR 3.00, 95% CI 0.31–28.81), and bexagliflozin (OR 1.50, 95% CI 0.06–36.99)...Conclusions SGLT2 inhibitors do not significantly alter the risk of PD. These findings support their neurological safety, though longer follow-up and dedicated neurodegenerative outcome trials are warranted."

Retrospective data • Cardiovascular • Chronic Kidney Disease • CNS Disorders • Congestive Heart Failure • Diabetes • Heart Failure • Metabolic Disorders • Movement Disorders • Nephrology • Parkinson's Disease • Renal Disease • Type 2 Diabetes Mellitus

Effects of individual sodium-glucose cotransporter-2 inhibitors on all-cause mortality in patients with diabetic kidney disease. (PubMed, Clin Exp Nephrol) - "Comparable effects of SGLT2is on all-cause mortality risk were observed in patients with DKD using the Asian real-world data. This apparent class effect on all-cause mortality suggests that different agents may confer comparable short-term mortality benefits when selected according to patient characteristics."

Journal • Diabetic Nephropathy • Nephrology • Renal Disease

SGLT2 INHIBITOR PREVENTS LOOP DIURETIC–INDUCED PLASMA VOLUME LOSS THROUGH A VASOPRESSIN-INDEPENDENT THIRSTSTIMULATING MECHANISM (ISN-WCN 2026) - "We recently reported that SGLT2 inhibitor–loop diuretic combination therapy preserves body fluid balance in chronic kidney disease (Front Med 2023, Diagnostics 2024), but the underlying mechanism remains unclear.Methods Non-diabetic male Sprague–Dawley rats were divided into four groups: vehicle (Veh), SGLT2 inhibitor ipragliflozin (Ipra; 5 mg/kg), loop diuretic furosemide (Furo; 50 mg/kg), and combination. Plasma renin activity and aldosterone were markedly increased in the combination group.Conclusion SGLT2 inhibitor–loop diuretic coadministration prevents diuretic-induced plasma volume contraction by stimulating thirst and fluid intake despite reduced AVP activity. This indicates a novel vasopressin-independent thirst mechanism contributing to maintenance of plasma volume during combined diuretic therapy.I have potential conflict of interest to disclose.Astellas Pharma provided ipragliflozin for this project.I did not use generative AI and AI-assisted technologies in..."

Chronic Kidney Disease • Nephrology • Renal Disease

The Effects of SGLT2 Inhibitors on Muscle Health in Older Adults: A Systematic Review and Meta-Analysis. (PubMed, Pharmacol Res Perspect) - "Subgroup analysis confirmed that fat mass was reduced with dapagliflozin/ipragliflozin (SMD = -0.67, p < 0.001; I2 = 26.4%) and empagliflozin (SMD = -0.53, p < 0.001; I2 = 66.4%). Although muscle mass declined modestly, the predominance of fat loss suggests weight reduction occurs through favorable metabolic changes. Given the slight muscle mass changes and study heterogeneity, careful monitoring in older adults is warranted, and further studies in diverse populations are needed."

Clinical • Journal • Retrospective data • Review • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Sarcopenia • Type 2 Diabetes Mellitus

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