Inpefa (sotagliflozin) / Lexicon Pharma - LARVOL DELTA

Unlocking the Potential of Sotagliflozin in Diabetes Mellitus targeting SGLT 1 & SGLT 2: A Comprehensive Review. (PubMed, Zhongguo Ying Yong Sheng Li Xue Za Zhi) - "However, its use is associated with some side effects, including gastrointestinal disturbances, urinary tract infections, and an elevated risk of diabetic ketoacidosis. This review explores the chemistry, pharmacology, and therapeutic implications of sotagliflozin, emphasizing its unique dual-target approach and potential to address unmet needs in diabetes management."

Journal • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Diabetes • Gastrointestinal Disorder • Heart Failure • Infectious Disease • Metabolic Disorders • Nephrology • Renal Disease • Type 2 Diabetes Mellitus • Urology

Cost-effectiveness analysis model for sotagliflozin compared with insulin monotherapy for patients with type 1 diabetes and chronic kidney disease. (PubMed, J Manag Care Spec Pharm) - "The ICER was $115,677 per QALY and the model was most sensitive to pharmacy costs. Sotagliflozin is a cost-effective adjunct to insulin therapy for T1D and CKD patients, providing clinical benefits and falling below the $150,000/QALY willingness-to-pay threshold in 59% of probabilistic sensitivity analysis simulations."

Clinical • HEOR • Journal • Monotherapy • Chronic Kidney Disease • Diabetes • Metabolic Disorders • Nephrology • Renal Disease • Transplantation • Type 1 Diabetes Mellitus

Cycloadditions as a Sweet Route to 'Double C-Glycosylation'. (PubMed, Biomolecules) - "Pharmaceuticals, such as the antibiotic erythromycin, and sodium-dependent glucose transporter (SGLT1 & SGTL2) inhibitors such as Bexagliflozin (diabetes) and Sotagliflozin (heart disease), are often sugar-decorated (glycosylated). The way in which this "double C-glycosylation" is naturally mediated is not yet known, yet has been speculated on. Here, we report the exploration and development of a potentially biomimetic procedure that utilises intermolecular cycloaddition chemistry to access new "double C-glycosylated" products and enables the creation of bridged polycyclic ethers from a common maltol-derived oxidopyrylium salt precursor."

Journal • Cardiovascular • Diabetes • Heart Failure • Metabolic Disorders

Sotagliflozin Added to Insulin Reduces the Risk of Clinically Important Hypoglycemic Events in Adults with Type 1 Diabetes Regardless of Kidney Function (ADA 2025) - "SOTA significantly reduced the risk of clinically important BG events ≤55 and ≤70 mg/dL, with a trend towards a reduction in severe hypoglycemic events in patients with T1D regardless of baseline kidney function."

Clinical • Diabetes • Hypoglycemia • Metabolic Disorders • Severe Hypoglycemia • Type 1 Diabetes Mellitus

The Broader Impact of Sotagliflozin—Meta-analysis of Its Efficacy in Diabetes Management, Cardiovascular Risk Reduction, and Renal Outcome (ADA 2025) - "Sotagliflozin demonstrates significant benefits in glycemic control and potential advantages in weight management and renal outcomes. However, uncertainties in cardiovascular safety and limited head-to-head comparisons with other therapies highlight the need for further high-quality studies to optimize its clinical use. These findings provide a foundation for advancing diabetes management strategies."

Retrospective data • Diabetes • Metabolic Disorders

Efficacy of sotagliflozin among older adults: a pooled analysis of SCORED and SOLOIST-WHF (ESC-WCC 2025) - No abstract available

Retrospective data • Cardiovascular

Safety and efficacy of adjuvant Sotagliflozin therapy in patients with T1D - an update and systematic review and meta-analysis. (PubMed, Front Endocrinol (Lausanne)) - "It also shows potential in lowering fracture risk, but the risk of DKA requires further clinical validation. https://www.crd.york.ac.uk/PROSPERO/#joinuppage, identifier CRD42023467427."

Journal • Retrospective data • Review • Cardiovascular • Chronic Kidney Disease • Diabetes • Hypoglycemia • Infectious Disease • Metabolic Disorders • Musculoskeletal Diseases • Nephrology • Oncology • Renal Disease • Type 1 Diabetes Mellitus

Impact of SGLT2 and Dual SGLT1/2 Inhibition on Salt-Sensitive Hypertension Progression in Dahl SS Rats (ERA 2025) - " Dahl salt-sensitive (SS) rats, a well-established model of salt-induced hypertension, were used to evaluate the effects of SGLT2 and dual SGLT1/2 inhibitors, dapagliflozin (Dapa) and sotagliflozin (Sota), respectively. This study demonstrates that SGLT2 and SGLT1/2 inhibition in a nondiabetic model of salt-sensitive hypertension attenuates the development and severity of salt-induced hypertension. Chronic SGLT2 inhibition enhances glucose and sodium excretion without impacting the expression or function of other sodium transporters and channels along the nephron or altering hormone levels in the renin-angiotensin-aldosterone system. Transcriptomic analyses of the kidney cortex identified lipid and amino acid metabolism, molecular transport, and cell function as the top biological pathways influenced by SGLT2 inhibition."

Preclinical • Cardiovascular • Congestive Heart Failure • Diabetic Nephropathy • Fibrosis • Heart Failure • Hypertension • Hypotension • Immunology • Metabolic Disorders • Renal Disease

COMPARATIVE EFFICACY AND SAFETY OF DIURETICS IN ACUTE DECOMPENSATED HEART FAILURE: A NETWORK META-ANALYSIS (ERA 2025) - "Loop diuretics, such as furosemide, are most often used as the diuretic of choice for diuresis, however, the optimal diuretic class for improving patient outcomes remains unclear... Among individual agents, empagliflozin (RR 0.50 [0.25, 0.98], p-score 0.8981) and hypertonic saline (HTS) (RR 0.55 [0.47, 0.64], p-score 0.8973) significantly reduced mortality. HTS and sotagliflozin demonstrated the greatest hospitalization risk reduction (RR 0.55 [0.49, 0.63], p- score 0.9447 and RR 0.74 [0.60, 0.92], p-score 0.7797, respectively). Tolvaptan and dapagliflozin were associated with non-improvement of dyspnea (RR 1.09 [1.05, 1.13], p-score 0.3821, and RR 1.40 [1.08, 1.81] p-value 0.0612, respectively), while no significant differences in hypotension were observed across treatment arms... This network meta-analysis comprehensively compares diuretic classes in ADHF, identifying HTS and MRA as the most effective in reducing mortality. SGLT2i demonstrated hospitalization reduction..."

Retrospective data • Cardiovascular • Congestive Heart Failure • Heart Failure • Hypotension • Pulmonary Disease

"Is sotagliflozin a 'wonder drug'? A review of its impact on cardiovascular, diabetic, renal, neuroprotective, and hepatic outcomes". (PubMed, Ann Med Surg (Lond)) - "Trials with other SGLT2 inhibitors, like dapagliflozin and empagliflozin, in HF, diabetes, and renal disease also showed significant reductions in major adverse cardiovascular events, hospitalizations, and improved kidney function. While adverse effects like hypoglycemia and ketoacidosis remain concerns, tailored dosing, and monitoring strategies may mitigate these risks. Thus, SGLT inhibitors, especially dual inhibitors like sotagliflozin, offer broad therapeutic benefits in diabetes, HF, CKD, and potentially neurological conditions."

Journal • Review • Alzheimer's Disease • Cardiovascular • Chronic Kidney Disease • CNS Disorders • Congestive Heart Failure • Diabetes • Diabetic Nephropathy • Heart Failure • Hypoglycemia • Inflammation • Metabolic Disorders • Movement Disorders • Nephrology • Parkinson's Disease • Renal Disease

Advances in Cardiovascular Pharmacotherapy. III. Sodium-Glucose Cotransporter Type 2 Inhibitors, Part 1: Efficacy in Heart Failure and Myocardial Infarction. (PubMed, J Cardiothorac Vasc Anesth) - "This two-part article provides an overview of SGLT2 inhibitor cardiovascular pharmacology. The first part briefly describes the physiology of SGLT2, including its role in glucose regulation and the impact of its inhibition in type 2 diabetes; discusses the safety trials indicating that these drugs had previously unrecognized advantages in patients with heart failure and atherosclerotic cardiovascular disease; and reviews the major clinical trials and their substudies demonstrating the efficacy of these medications across heart failure phenotypes and in myocardial infarction."

Clinical • Journal • Review • Atherosclerosis • Cardiovascular • Congestive Heart Failure • Diabetes • Heart Failure • Metabolic Disorders • Myocardial Infarction • Type 2 Diabetes Mellitus

Sotagliflozin: Two Birds with One Stone? (PubMed, Cardiovasc Drugs Ther) - "These observations suggest that dual SGLT1-2 inhibition may offer additional benefits over single SGLT2-i. Further comparative and mechanistic studies are required to understand and differentiate the clinical impact of SGLT2i vs. SGLT1-2i, particularly in non-diabetic HF patients."

Journal • Review • Cardiovascular • Congestive Heart Failure • Diabetes • Fibrosis • Heart Failure • Hematological Disorders • Immunology • Metabolic Disorders • Myocardial Infarction • Thrombosis

In type 2 diabetes with CKD and additional CV risk factors, sotagliflozin reduced total MACE vs. placebo at a median 14 mo. (PubMed, Ann Intern Med) - "GIM/FP/GP: [Formula: see text] Cardiology: [Formula: see text] Endocrinology: [Formula: see text] Nephrology: [Formula: see text]."

Journal • Cardiovascular • Diabetes • Endocrine Disorders • Metabolic Disorders • Nephrology • Type 2 Diabetes Mellitus

SGLT2 Inhibitors in Cancer Patients: A Comprehensive Review of Clinical, Biochemical, and Therapeutic Implications in Cardio-Oncology. (PubMed, Int J Mol Sci) - "Among the currently available SGLT2i, such as empagliflozin, canagliflozin, dapagliflozin, and sotagliflozin, there is growing evidence supporting their role in reducing major adverse cardiovascular events (MACEs), hospitalization for heart failure, and the progression of chronic kidney disease. We explore the common pathophysiological pathways between cardiovascular dysfunction and cancer, the molecular rationale for the use of SGLT2is in cancer patients, and the potential benefits in both primary and secondary prevention of cardiovascular toxicity related to oncological treatments. The aim is to propose a therapeutic paradigm utilizing SGLT2is to reduce cardiovascular mortality, MACE, and the burden of cardiotoxicity in high-risk oncology patients, fostering an integrated approach to cardio-oncology care."

Journal • Review • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Coronary Artery Disease • Diabetes • Fibrosis • Heart Failure • Immunology • Metabolic Disorders • Nephrology • Oncology • Renal Disease • Type 2 Diabetes Mellitus • MYD88 • NLRP3

Synergistically enhanced Ni-MOF/CNTs nanocomposite as an electrochemical platform for ultrasensitive determination of sotagliflozin in various matrices, with whiteness and blueness assessments. (PubMed, Mikrochim Acta) - "The sensor's outstanding performance addresses the unmet need for a simple and accurate tool for sotagliflozin determination in biological and pharmaceutical samples, as no existing analytical methods are available for its determination in different matrices. This makes it a valuable tool for sotagliflozin therapeutic drug monitoring, point-of-care diagnostics, and quality control."

Journal

Comparison chart: Some drugs for HFrEF. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure

Drugs for chronic heart failure. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure

Efficacy and safety of sotagliflozin in patients with symptomatic obstructive and non-obstructive hypertrophic cardiomyopathy (SONATA-HCM): study design (HEART FAILURE 2025) - "The findings could demonstrate that dual SGLT1 and SGLT2 inhibition with sotagliflozin is a therapeutic option to improve disease-specific symptoms and physical limitations in patients with symptomatic HCM."

Clinical • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure • Hypertrophic Cardiomyopathy • Non-obstructive Hypertrophic Cardiomyopathy • Obstructive Hypertrophic Cardiomyopathy • TNNI3

Type 2 diabetes mellitus - conventional therapies and future perspectives in innovative treatment. (PubMed, Biochem Biophys Rep) - "Conventional therapies, including metformin, sulfonylureas, and insulin, have long served as the cornerstone of treatment...Recent advances in diabetes management feature dual incretin receptor agonists, like tirzepatide, which combine GLP-1 and GIP receptor agonism, resulting in increased insulin secretion, decreased glucagon release, and significant weight loss. Additionally, dual SGLT1/2 inhibitors, such as sotagliflozin, show promise for more significant blood glucose reduction and improved weight loss by targeting glucose regulation in both the gut and kidneys...This article reviews the conventional therapies currently in use. It investigates future perspectives on innovative treatments for T2DM, emphasizing the potential of these new therapies to transform diabetes care and enhance patient outcomes."

Journal • Review • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus • FGF21

Evaluating Sotagliflozin Effects on HbA1c and Body Weight across Stages of Diabetic Kidney Disease (AACE 2025) - "Approximately 20-40% of patients with diabetes develop chronic kidney disease (CKD), a condition characterized by albuminuria and a reduced estimated glomerular filtration rate (eGFR). Investigating the impact of dual inhibitors of SGLT-1/2 on glycemic control across various stages of CKD will support clinical decision-making."

Chronic Kidney Disease • Diabetes • Diabetic Nephropathy • Metabolic Disorders • Nephrology • Renal Disease

Cost-Effectiveness of Sotagliflozin for Patients With Type 1 Diabetes and Chronic Kidney Disease, With and Without Dynamic Pricing (ISPOR 2025) - "Sotagliflozin with insulin offers a cost-effective strategy for improving health outcomes in patients with T1D and CKD. Not accounting for dynamic pricing may underestimate the value of add-on therapies like sotagliflozin."

Clinical • Cost effectiveness • HEOR • Pricing • Chronic Kidney Disease • Diabetes • Metabolic Disorders • Nephrology • Renal Disease • Type 1 Diabetes Mellitus

Efficacy and Safety of Sotagliflozin in Patients with Type 1 Diabetes by Kidney Function, A Subgroup Analysis of the inTandem trials (ESPE-ESE 2025) - "Sotagliflozin, when added to optimized insulin, demonstrated improvements in glycemic control, reduction in SBP, and insulin dose reduction in groups with higher eGFR. Benefits in weight loss was observed across varying degrees of kidney function. Most favorable safety profile was seen in patients with preserved kidney function."

Clinical • Late-breaking abstract • Diabetes • Metabolic Disorders • Severe Hypoglycemia • Type 1 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

SGLT2 inhibitors Use in Kidney Disease: What Did We Learn? (PubMed, Am J Physiol Endocrinol Metab) - "Post marketing cardiovascular outcome trials (CVOT) have demonstrated improved cardiovascular outcomes with use of sodium-glucose cotransporter-2 inhibitors SGLT2i) like canagliflozin, dapagliflozin, empagliflozin, ertugliflozin, and sotagliflozin in patients with type 2 diabetes mellitus (T2DM), Similarly, secondary analysis of CVOT and renal outcome trials with the use of SGLT2i in patients without T2DM showed improved renal function and albuminuria. Based on our research of published literature, we present a review and propose, consideration of SGLT2i in non-diabetic kidney disease for long term cardiovascular and renal benefit (1). We will highlight relevant translational studies to propose a possible cell-based mechanism for cardiovascular benefits noted secondary to use of SGLT2i."

Journal • Review • Cardiovascular • Chronic Kidney Disease • Diabetic Nephropathy • Fibrosis • Immunology • Inflammation • Metabolic Disorders • Nephrology • Renal Disease • Type 2 Diabetes Mellitus

ASPIRE: Ambrisentan Sotagliflozin and Prevention of Renal Injury; a Randomized Evaluation (clinicaltrials.gov) - P2 | N=36 | Not yet recruiting | Sponsor: University Medical Center Groningen | Trial completion date: Mar 2025 ➔ Dec 2027 | Trial primary completion date: Mar 2025 ➔ Sep 2027

Trial completion date • Trial primary completion date • Chronic Kidney Disease • Diabetes • Diabetic Nephropathy • Metabolic Disorders • Nephrology • Renal Disease • Type 1 Diabetes Mellitus