Farxiga (dapagliflozin) / Ono Pharma, AstraZeneca - LARVOL DELTA

Dual Inhibition Strategy in Managing Neuronal Autophagy in PTZ-Induced Kindling in Mice: A Pharmacological Perspective on P2Y12 and SGLT2 Inhibitors. (PubMed, Eur J Pharmacol) - "This study demonstrated neuroprotective potential of dapagliflozin and ticagrelor in PTZ-induced kindling model. The therapy mitigated oxidative stress, restored E/I neurotransmission, promoted GABA receptor trafficking, and maintained neuronal integrity, suggesting its promising role in managing epilepsy."

Journal • Preclinical • CNS Disorders • Epilepsy • AMPK • BECN1 • GABARAP • mTOR • SQSTM1

DAPA-ICU: Dapagliflozin for Cardio-renal Protection After ICU Discharge (clinicaltrials.gov) - P3 | N=600 | Recruiting | Sponsor: Assistance Publique - Hôpitaux de Paris | Not yet recruiting ➔ Recruiting | Trial completion date: Oct 2028 ➔ Jan 2029 | Initiation date: Sep 2025 ➔ Dec 2025 | Trial primary completion date: Oct 2028 ➔ Jan 2029

Enrollment open • Trial completion date • Trial initiation date • Trial primary completion date • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Heart Failure • Nephrology • Renal Disease

Efficacy, Mechanisms and Safety of Sodium-Glucose Cotransporter-2 Inhibitors in Kidney Transplant Recipients: A Randomized, Double-Blind, Placebo-Controlled Trial. (PubMed, Clin J Am Soc Nephrol) - "Dapagliflozin activated expected physiological pathways, though key differences observed in KTR might suggest mechanistic heterogeneity compared to non-transplant populations. Clinical trials evaluating SGLT2 inhibitors in KTR are important to determine whether these mechanistic effects translate to improvements in kidney and cardiovascular outcomes."

Clinical • Journal • Cardiovascular • Diabetes • Hypertension • Infectious Disease • Metabolic Disorders • Transplantation • Type 2 Diabetes Mellitus • Urology

Design, Optimization, and Biological Evaluation of First-in-Class Triple Inhibitors of SGLT1, SGLT2, and DPP4 for Type 2 Diabetes Mellitus. (PubMed, J Med Chem) - "Following oral glucose challenge in Zucker diabetic rats, they demonstrated statistically superior plasma glycemic control versus SGLT2-selective inhibitor dapagliflozin and conferred a prolonged increase in active GLP-1 relative to the SGLT1/2 inhibitor sotagliflozin, implying synergistic SGLT1 and DPP4 inhibition. These results support triple-targeted inhibitors as multitarget, multiorgan drug candidates for improved glycemic control and cardiorenal benefits."

Journal • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Effectiveness of second-line therapies following upfront daratumumab plus bortezomib, cyclophosphamide and dexamethasone: A new benchmark (ASH 2025) - "Consolidative high dose melphalan and autologousstem cell transplant (HDM/ASCT) after achieving an optimal hematologic response to L1 (N=17) wasincluded in L1...For 2L, 19 (34%) ptsreceived a venetoclax (VEN)-based regimen including VEN monotherapy, VEN-daratumumab, VEN-pomalidomide, VEN-bortezomib or VEN-bortezomib-daratumumab...Four received HDM/ASCT, while others had various combinations of daratumumab,bortezomib, ixazomib, carfilzomib, lenalidomide, pomalidomide, cyclophosphamide, elotuzumab,dapagliflozin and bendamustine.Hematologic responses to L2 included 15 (31%) CR, 12 (25%) VGPR, 8 (17%) low dFLC PR and 13 (27%) PRor less...Data from two additional sites will be added to the dataset by09/2025. These multicenter data will serve as a benchmark for new drug approval in the non-responderand relapsed setting."

Clinical • Amyloidosis

Real-world Pharmacovigilance Study of Drug-induced Diabetes Insipidus from the FAERS Database. (PubMed, Endocr Connect) - "Lithium (n = 114, Information Component at the 95% lower credibility interval [IC025] = 6.12) and dexmedetomidine (n = 105, IC025 = 6.79) were identified as the most frequently reported drugs and showed the strongest association with DI. Several drugs, such as aripiprazole, letrozole, tigecycline, and dapagliflozin, were found to have unexpected potential associations with DI. This study provides a comprehensive overview of drug-induced DI based on real-world data. It highlights the importance of monitoring patients for DI when using certain medications, particularly high-risk nervous system drugs and antineoplastic agents."

Adverse events • Journal • Real-world evidence • Metabolic Disorders • Oncology

Dapagliflozin for treatment of sickle cell nephropathy: A multi-centre experience (ASH 2025) - "Thirty-five patients (90%)were receiving disease-modifying therapy for sickle cell disease (23 patients taking hydroxyurea and 12patients on a regular transfusion programme). Six patients were also prescribed anti-hypertensivetherapy (amlodipine, doxazosin or indapamide) and 6 patients were prescribed erythropoietinstimulating agents (ESA).Mean eGFR prior to starting dapagliflozin was 50ml/min/1.73m2 (standard deviation 14ml/min/1.73m2).There was a small reduction in eGFR shortly after commencing dapagliflozin treatment: mean decreaseof 5ml/min/1.73m2 (95% confidence interval 2-7ml/min/1.73m2, P<0.001), evaluated in 36 patients witheGFR measured at least one month (median 4.5months) after starting dapagliflozin...Dapagliflozinappeared generally well tolerated, with a few patients experiencing a recognised complication of urinarytract infections. A small rise in creatinine is expected during initial treatment due to a reduction inintraglomerular pressure caused by..."

Clinical • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Diabetes • Diabetic Nephropathy • Genetic Disorders • Heart Failure • Hematological Disorders • Hypertension • Infectious Disease • Metabolic Disorders • Nephrology • Renal Disease • Sickle Cell Disease • Type 2 Diabetes Mellitus

Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitors and Risk of Heart Failure Hospitalization in Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. (PubMed, Cureus) - "This benefit was consistent across most agents, including empagliflozin, canagliflozin, dapagliflozin, and sotagliflozin, while ertugliflozin showed a nonsignificant trend in the same direction. The results demonstrate that SGLT2 inhibitors confer clinically meaningful cardiorenal protection that is recognized to occur through mechanisms largely independent of glucose lowering, reinforcing their role as cornerstone agents in the management of T2DM. These findings highlight the importance of prioritizing SGLT2 inhibitors in contemporary diabetes care to reduce the global burden of heart failure (HF)."

Journal • Retrospective data • Review • Atherosclerosis • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Diabetes • Heart Failure • Metabolic Disorders • Nephrology • Renal Disease • Type 2 Diabetes Mellitus

Analysis of the Effects of Dapagliflozin on Cardiac Myocyte Injury Markers and Left Ventricular Diastolic Function in Heart Failure Patients with Preserved Ejection Fraction after PCI. (PubMed, Eur J Transl Myol) - "Dapagliflozin effectively reduces cardiac myocyte injury markers, improves left ventricular diastolic function, and lowers the incidence of MACE in HF-PEF patients after PCI, demonstrating significant translational benefits for cardiac muscle function."

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure • TNNI3

Efficacy and safety of pioglitazone versus dapagliflozin as an add-on to metformin and alogliptin combination therapy: the EPIDOTE study. (PubMed, Sci Rep) - "Pioglitazone added to metformin and alogliptin significantly improved glycemic control in patients with type 2 diabetes, and was non-inferior to dapagliflozin. This study suggests that pioglitazone could be an effective and safe option for patients with inadequate glycemic control on metformin and DPP4i."

Journal • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Comparative Long-Term Cardiovascular Outcomes of Empagliflozin and Dapagliflozin in Heart Failure Patients After Coronary Revascularization: A Retrospective Cohort Study. (PubMed, J Clin Med) - " In this real-world cohort of revascularized HF patients, empagliflozin and dapagliflozin demonstrated comparable long-term cardiovascular outcomes, supporting a class effect of SGLT2 inhibitors in this high-risk population. Beyond pharmacologic comparison, age and AF emerged as dynamic predictors of cardiac MACE, highlighting the importance of longitudinal, time-dependent risk assessment in heart failure management following coronary revascularization."

Journal • Retrospective data • Atrial Fibrillation • Cardiovascular • Congestive Heart Failure • Heart Failure

Heart failure with preserved ejection fraction: current insights and emerging therapeutic directions. (PubMed, Korean J Physiol Pharmacol) - "Empagliflozin significantly reduced the risk of cardiovascular death or heart failure hospitalization and dapagliflozin demonstrated comparable efficacy across regions. In numerous respects, the clinical and pathophysiological features of HFpEF in Asian populations diverge from those traditionally observed in Western cohorts. In this brief review, we will focus on therapeutics approved for HFpEF and agents currently under clinical trial, as well as the distinctive characteristics of HFpEF patients observed in Asia and the key considerations for future therapeutic development in this region."

Journal • Review • Cardiovascular • Congestive Heart Failure • Diabetes • Genetic Disorders • Heart Failure • Hypertension • Metabolic Disorders • Obesity

Effects of zibotentan and dapagliflozin combined in patients with compensated cirrhosis: A randomized placebo-controlled exploratory study. (PubMed, Br J Clin Pharmacol) - "Combined zibo/dapa was well tolerated and had a good safety profile in patients with compensated cirrhosis, but had no conclusive effect on HVPG."

Journal • Cardiovascular • Fibrosis • Hepatology • Hypertension • Immunology • Liver Failure • Metabolic Disorders • Portal Hypertension

A Case of Slowly Progressive Type 1 Diabetes Mellitus (SPIDDM, Probable) Successfully Managed With Oral Semaglutide for Glycemic Control and Weight Management Accompanied by Changes in Eating Behavior. (PubMed, Cureus) - "We report a case of a 23-year-old Japanese woman who had SPIDDM (probable) since the age of 19 and had poor glycemic and weight control despite treatment with insulin, dapagliflozin, and metformin. Notably, beneficial changes in her eating behavior were also evident after oral semaglutide administration. This case suggests that GLP-1 RAs are a beneficial therapeutic option for glucose and weight management in patients with SPIDDM (probable), particularly when accompanied by favorable alterations in eating behavior, thus warranting further investigation."

Journal • Diabetes • Immunology • Metabolic Disorders • Type 1 Diabetes Mellitus

When Falls Reveal Acidosis: Unmasking Sodium-Glucose Co-transporter 2 (SGLT2) Inhibitor-Induced Euglycemic Diabetic Ketoacidosis. (PubMed, Cureus) - "Dapagliflozin was discontinued, and she was treated successfully with IV insulin and aggressive fluid resuscitation. This case illustrates the importance of maintaining a high index of suspicion for euDKA in elderly patients on SGLT2 inhibitors, particularly when presenting with nonspecific symptoms such as confusion or falls. Early recognition, prompt discontinuation of the SGLT2 inhibitor, and appropriate management are critical to improving outcomes."

Journal • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

The RENAL LIFECYCLE Trial: A RCT to Assess the Effect of Dapagliflozin on Renal and Cardiovascular Outcomes in Patients With Severe CKD (clinicaltrials.gov) - P3 | N=1750 | Enrolling by invitation | Sponsor: University Medical Center Groningen | Trial completion date: Jan 2027 ➔ Jul 2027 | Trial primary completion date: Jan 2027 ➔ Jul 2027

Trial completion date • Trial primary completion date • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Heart Failure • Nephrology • Renal Disease • Transplantation

Meta-analysis of clinically available pharmacotherapy of biopsy confirmed metabolic dysfunction associated steatohepatitis (MASH). (PubMed, Diabetes Obes Metab) - "Clinically available medications are beneficial in reversing MASH. Improvements in RSw/oF and RFw/oS were greater at earlier stages of fibrosis. Future analyses of drug effects should include assessments adjusted for baseline study characteristics of Fibrosis Grades and may evaluate whether preventive therapy will have long term benefits if started at earlier stages of MASLD."

Journal • Retrospective data • Fibrosis • Hepatitis C • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease

OPTIMAR: Optimising Metabolic Management for People With Human Immunodeficiency Virus (HIV) on Integrase Based Antiretroviral Therapy (ART) (clinicaltrials.gov) - P3 | N=300 | Active, not recruiting | Sponsor: Kirby Institute | Recruiting ➔ Active, not recruiting

Enrollment closed • Congestive Heart Failure • Human Immunodeficiency Virus • Infectious Disease

The effect of SGLT2 inhibitor and HIF-PHI on the podocyte-specific molecules and cytoskeleton of diabetic podocytes. (PubMed, BMC Nephrol) - "SGLT2i Dapagliflozin and HIF-PHI Roxadustat partly restore the podocyte morphology and intracellular mRNA and protein levels of podocyte-associated molecule in a diabetic milieu."

Journal • Chronic Kidney Disease • Diabetes • Diabetic Nephropathy • Hematological Disorders • Metabolic Disorders • Nephrology • Renal Disease • NPHS1 • PODXL

Empagliflozin and Dapagliflozin Outcomes in Heart Failure. (PubMed, JAMA Netw Open) - "In this cohort study of patients with HF, dapagliflozin and empagliflozin had similar clinical outcomes in HF management. Further research and clinical trials are necessary to validate these findings and inform clinical decision-making."

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure

New Horizons in Diabetic Neuropathy: Highlights from the 2025 ADA and EASD Conferences. (PubMed, Int J Low Extrem Wounds) - "Therapeutically, dapagliflozin promoted corneal nerve regeneration through anti-inflammatory pathways...Basic science studies elucidated new mechanisms, including Schwann cell ferroptosis, and a gut-brain axis contributing to neuropathic pain and cognitive decline. Taken together, these findings promote our understanding of DN pathophysiology and therapy."

Journal • Review • Cardiovascular • CNS Disorders • Congestive Heart Failure • Diabetes • Diabetic Neuropathy • Heart Failure • Metabolic Disorders • Myocardial Infarction • Neuralgia • Pain • Peripheral Neuropathic Pain • Type 1 Diabetes Mellitus • Type 2 Diabetes Mellitus

Sodium-Glucose Cotransporter-2 Inhibitor for Patients With Acute Cardiorenal Syndrome (clinicaltrials.gov) - P2 | N=130 | Not yet recruiting | Sponsor: Yale University

New P2 trial • Acute Kidney Injury • Cardiovascular • Congestive Heart Failure • Heart Failure • Nephrology • Renal Disease

Dapagliflozin in acute heart failure: lessons from the DAPA ACT HF-TIMI 68 trial. (PubMed, Heart Fail Rev) - No abstract available

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure

Efficacy and safety of dapagliflozin in inactive lupus nephritis: a randomized crossover trial. (PubMed, Nephrol Dial Transplant) - "We demonstrate a significant reduction in residual proteinuria in patients with inactive LN with dapagliflozin without safety concerns."

Journal • Diabetes • Glomerulonephritis • Hypotension • Immunology • Infectious Disease • Inflammatory Arthritis • Lupus • Lupus Nephritis • Metabolic Disorders • Nephrology • Renal Disease • Urology

The concentration-dependent protective effects by new generation hypoglycemic agents on delirium, depression, dementia and coma: evidence from a network meta-analysis. (PubMed, J R Soc Med) - "This analysis highlights agent-specific neuroprotective profiles: SGLT2 inhibitors, especially high-dose dapagliflozin, may mitigate the onset of delirium and depression, while GLP-1 receptor agonists, notably dulaglutide and liraglutide, may enhance cognitive function. These findings warrant consideration in selecting antihyperglycemic therapies for individuals at elevated neuropsychiatric risk."

Journal • Retrospective data • Alzheimer's Disease • CNS Disorders • Dementia • Depression • Diabetes • Mental Retardation • Metabolic Disorders • Mood Disorders • Psychiatry • Type 2 Diabetes Mellitus