Suglat (ipragliflozin) / EMD Serono, Kotobuki, Astellas - LARVOL DELTA

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

ZNF480 Accelerates Chemotherapy Resistance in Breast Cancer by Competing With TRIM28 and Stabilizing LSD1 to Upregulate the AKT-GSK3β-Snail Pathway. (PubMed, Mol Carcinog) - "Ipragliflozin was identified as a small-molecule inhibitor of ZNF480 and LSD1 interaction that may block breast cancer progression...Mechanistically, ZNF480 accelerates proliferation and neoadjuvant chemotherapy resistance in breast cancer cells via the AKT-GSK3β-Snail pathway by interacting with and stabilizing LSD1 in a competitive manner within TRIM28. This research has implications for developing targeted drugs against chemotherapy resistance in breast cancer."

Journal • Breast Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • TRIM28 • ZNF480

BALANCE: A Study to Evaluate the Effect of ASP1941 in Combination With Metformin in Adult Patients With Type 2 Diabetes Mellitus (clinicaltrials.gov) - P2 | N=343 | Completed | Sponsor: Astellas Pharma Inc | Phase classification: P2b ➔ P2

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

Effects of ipragliflozin on skeletal muscle adiposity in patients with diabetes and metabolic dysfunction-associated steatotic liver disease. (PubMed, Intern Med) - "Regardless of the treatment, a specific phenotype of adiposity and hepatic steatosis before treatment is associated with the long-term outcomes of myosteatosis. Maintaining skeletal muscle mass and better glycemic control during treatment are essential for the future improvement of myosteatosis."

Journal • Diabetes • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • Sarcopenia • Type 2 Diabetes Mellitus

Drug repurposing: An antidiabetic drug Ipragliflozin as Mycobacterium tuberculosis sirtuin-like protein inhibitor that synergizes with anti-tuberculosis drug isoniazid. (PubMed, Int J Biol Macromol) - "It can potentiate the first-front anti-TB drug isoniazid. As an antidiabetic drug, Ipragliflozin can be potentially included in the regimen to treat diabetes-tuberculosis comorbidity."

Journal • Diabetes • Infectious Disease • Metabolic Disorders • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Additive Diuretic Action of SGLT2 Inhibitor and Loop Diuretic Combination Avoids Body Fluid Loss by Promoting Vasopressin-Independent Compensatory Fluid Intake (KIDNEY WEEK 2024) - "In addition, we recently reported that the combination of SGLT2 inhibitor and loop diuretic maintains body fluid balance in chronic kidney disease patients (Front Med 2023), but the mechanism remains unclear. Non-diabetic Sprague-Dawley rats were divided into 4 groups: 1) Vehicle (Veh), 2) SGLT2 inhibitor ipragliflozin 5 mg/kg (Ipra), 3) loop diuretic furosemide 50 mg/kg (Furo), and 4) ipragliflozin and furosemide combination (Ipra+Furo) with free access to fluid and normal rodent chow. Combination of SGLT2 inhibitor and loop diuretic avoided body fluid loss by promoting compensatory fluid intake despite suppressed AVP tone and absence of serum Na+ and osmolality increase. These results may indicate a novel non-osmoregulatory thirst mechanism induced by the combination of SGLT2 inhibitors and loop diuretics."

Chronic Kidney Disease • Nephrology • Renal Disease

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

Water and sodium conservation response induced by SGLT2 inhibitor ipragliflozin in Dahl salt-sensitive hypertensive rats. (PubMed, Hypertens Res) - "A high-salt diet significantly increased systolic blood pressure, but ipragliflozin did not significantly change systolic blood pressure in normal- or high-salt groups. In conclusion, SGLT2 inhibitor ipragliflozin did not change fluid and Na+ balance regardless of basal fluid retention, suggesting the potential of SGLT2 inhibitors to maintain body water and Na+."

Journal • Preclinical

Exploring the Anti-Cancer Potential of SGLT2 Inhibitors in Breast Cancer Treatment in Pre-clinical and Clinical Studies. (PubMed, Eur J Pharmacol) - "Preclinical studies have demonstrated that various SGLT2 inhibitors, such as canagliflozin, dapagliflozin, ipragliflozin, and empagliflozin, can inhibit the proliferation of breast cancer cells, induce apoptosis, and modulate key cellular signaling pathways. Ongoing and future clinical trials investigating the use of SGLT2 inhibitors, both as monotherapy and in combination with other agents, will be crucial in elucidating their translational potential and guiding their integration into comprehensive breast cancer care. Overall, SGLT2 inhibitors represent a novel and promising therapeutic approach with the potential to improve clinical outcomes for patients with various subtypes of breast cancer, including the aggressive and chemo-resistant TNBC."

Journal • Preclinical • Review • Breast Cancer • Diabetes • Metabolic Disorders • Oncology • Solid Tumor • Triple Negative Breast Cancer • Type 2 Diabetes Mellitus • AMPK

Effects of Ipragliflozin and Metformin on Hepatic Steatosis and Liver Fibrosis (ADA 2024) - "Compared with metformin, ipragliflozin significantly improved multiple hepatic steatosis and liver fibrosis indexes, suggesting that ipragliflozin may alleviate hepatic steatosis, prevent liver fibrosis progression, and improve glycemic control. Therefore, it may prevent MASLD/MASH."

Diabetes • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • Type 2 Diabetes Mellitus

Real-World Study of the Efficacy of an Adjunctive Use of Ipragliflozin for Prevention of Chronic Kidney Disease in People with Type 1 Diabetes (IPRA-CKD)—A Multicenter Retrospective Study (ADA 2024) - "This real-world study indicated that 24 months of adjunctive IPRA treatment might benefit glycemic control but did not significantly improve kidney function compared to insulin monotherapy in people with T1D."

Real-world • Real-world evidence • Retrospective data • Diabetes • Metabolic Disorders • Severe Hypoglycemia • Type 1 Diabetes Mellitus • Type 2 Diabetes Mellitus

Long-term effects of different hypoglycemic drugs on carotid intima-media thickness progression: a systematic review and network meta-analysis. (PubMed, Front Endocrinol (Lausanne)) - "This network meta-analysis compared the effects of 14 antidiabetic drugs (acarbose, alogliptin, exenatide, glibenclamide, glimepiride, ipragliflozin, metformin, nateglinide, pioglitazone, rosiglitazone, sitagliptin, tofoglifozin, troglitazone, voglibose) on the progression of cIMT. Long-term treatment of exenatide, alogliptin, and metformin may be more effective than other hypoglycemic drugs in slowing the progression of cIMT. https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024519474."

Clinical • Journal • Retrospective data • Review • Atherosclerosis • Cardiovascular • Diabetes • Dyslipidemia • Metabolic Disorders

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

Effect of ipragliflozin on liver enzymes in type 2 diabetes mellitus: a meta-analysis of randomized controlled trials. (PubMed, Expert Opin Pharmacother) - "Findings suggest the beneficial effects of ipragliflozin on liver enzymes. Further large-scale RCTs are required to confirm ipragliflozin's role for liver-related conditions in T2DM."

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