Inpefa (sotagliflozin) / Lexicon Pharma - LARVOL DELTA

Comparative Cardiorenal Efficacy and Safety of Finerenone, SGLT2 Inhibitors, Semaglutide and Their Combination in Diabetic Kidney Disease. (PubMed, Diabetes Obes Metab) - "SGLT2i showed the broadest cardiorenal benefits, while finerenone and semaglutide provided additional protection across selected outcomes. Finerenone increased hyperkalaemia and treatment discontinuation. The efficacy of finerenone-SGLT2i combination therapy requires further investigation."

Journal • Cardiovascular • Diabetes • Diabetic Nephropathy • Metabolic Disorders • Nephrology • Renal Disease • Type 2 Diabetes Mellitus

SGLT2 Inhibitors in Cardiovascular-Kidney-Metabolic Syndrome: Drugs Unifying Heart, Kidney, and Metabolism Pharmacotherapy. (PubMed, Am J Cardiovasc Drugs) - "Importantly, SGLT2 inhibitors such as canagliflozin, dapagliflozin, empagliflozin, and sotagliflozin were well tolerated, though caution is advised in volume-depleted patients or those at risk for genitourinary infections. Positive effects, ranging from glycemic control to renoprotective and cardioprotective properties, support SGLT2 inhibitors as first-line therapy in improving clinical outcomes and quality of life in patients affected by this interconnected disease spectrum."

Journal • Review • Cardiovascular • Chronic Kidney Disease • Diabetes • Infectious Disease • Metabolic Disorders • Nephrology • Renal Disease • Type 2 Diabetes Mellitus • Urology

Effects of Sotagliflozin and Empagliflozin on Thrombus Formation in Healthy Volunteers: A Randomized Crossover Trial (AHA 2026) - "Abstract is embargoed at this time."

Clinical • Thrombosis

Sotagliflozin Synergizes with ETI to Ameliorate NASH-Like Pathology in Cystic Fibrosis Rabbits (NACFC 2026) - "Background: While Elexacaftor/tezacaftor/ivacaftor (ETI) has transformed pulmonary outcomes and life expectancy in cystic fibrosis (CF), extrapulmonary manifestations such as CF-related hepatobiliary involvement (CFHBI) remain a challenge. While ETI improves survival and general body condition, it is insufficient to fully resolve liver manifestations in CF rabbits. The addition of Sota to ETI produces a robust synergistic effect, reversing hepatic steatosis and significantly reducing hepatic and biliary fibrosis. These data suggest that SGLT inhibition addresses metabolic and inflammatory pathways refractory to CFTR modulator, positioning sota as a potent adjunct treatment for CFHBI."

Preclinical • Cystic Fibrosis • Fibrosis • Genetic Disorders • Hepatology • Immunology • Inflammation • Metabolic Dysfunction-Associated Steatohepatitis • Respiratory Diseases

Influence of hsCRP on treatment response to sotagliflozin in type 1 diabetes (EASD 2026) - P3 | "Nearly 40% of participants had an hsCRP level suggestive of high CV risk. Although the A1C efficacy response to adjunctive sotagliflozin was generally consistent across the hsCRP categories in participants with T1D, there was a trend for a larger response in those with elevated hsCRP."

Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus • CRP

Sotagliflozin, a Dual SGLT1/2 Inhibitor, Modulates DNMT1 and Class I/II HDAC Expression in Association With Anticancer Effects in Breast and Lung Cancer Cells. (PubMed, Cell Biol Int) - "Collectively, these findings demonstrate that sotagliflozin exerts broad anticancer effects in breast and lung cancer cells and provide preliminary evidence that its treatment is associated with modulation of DNMT1 and HDAC expression. Further studies are required to determine whether these epigenetic changes contribute directly to the observed cellular responses or represent downstream consequences of metabolic perturbation."

Journal • Breast Cancer • Lung Cancer • Oncology • Solid Tumor • BECN1 • DNMT1 • DNMT3A • DNMT3B • HDAC1 • PTEN

Benefits of sotagliflozin across the full range of baseline blood pressure in the SOLOIST-WHF Trial (ESC 2026) - "Furthermore, initiation of sotagliflozin in patients with low SBP was not associated with an increased incidence of AKI and hypotension. These results support the initiation of SGLT inhibition during hospitalization even in heart failure patients with “borderline” SBP."

Cardiovascular • Congestive Heart Failure • Heart Failure • Hypotension

Effects of SGLT2 inhibitors on the atrial rhythm: Sotagliflozin modifies the activity of NaV1.5 (ESC 2026) - "Beyond metabolic and hemodynamic effects, emerging evidence suggests that SGLT2i may exert direct antiarrhythmic effects, as subanalyses of large clinical trials have shown reduced incidence of atrial arrhythmias in patients treated with dapagliflozin. This finding indicates a direct interaction of sotagliflozin with the NaV1.5 binding site, consistent with results from in silico docking analysis.ConclusionSotagliflozin interacts with NaV1.5 channels through a direct pore-binding mechanism, leading to a peak current inhibition and altered activation kinetics. These findings identify NaV1.5 as a molecular target of sotagliflozin and indicate a potential mechanism contributing to the antiarrhythmic effects observed in clinical studies."

Cardiovascular • Congestive Heart Failure • Heart Failure • NAV1

Benefit of Sotagliflozin Across the Full Range of Baseline Blood Pressure in the SOLOIST-WHF Trial. (PubMed, JACC Heart Fail) - No abstract available

Journal

Mitigating DKA in Type 1 Diabetes for Safe Use of SGLT Inhibitors Using Dual Continuous Ketone and Glucose Monitoring. (clinicaltrials.gov) - P2 | N=80 | Not yet recruiting | Sponsor: HealthPartners Institute | Trial completion date: Aug 2028 ➔ Feb 2030 | Trial primary completion date: May 2028 ➔ Feb 2029

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

SONATA-HCM: A Study to Evaluate the Efficacy and Safety of Sotagliflozin in Symptomatic Obstructive and Non-obstructive Hypertrophic Cardiomyopathy (clinicaltrials.gov) - P3 | N=500 | Active, not recruiting | Sponsor: Lexicon Pharmaceuticals | Trial completion date: Aug 2026 ➔ Feb 2027 | Trial primary completion date: Jul 2026 ➔ Jan 2027

Trial completion date • Trial primary completion date • Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy • Non-obstructive Hypertrophic Cardiomyopathy • Obstructive Hypertrophic Cardiomyopathy

Effect of Sotagliflozin on Kidney Function and Cardio-Kidney-Metabolic Parameters Across Baseline eGFR Subgroups in Patients With Type 2 Diabetes and Stage 4 CKD. (PubMed, Diabetes Obes Metab) - No abstract available

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

Non-anomeric glycoboranes: Synthesis and application to the construction of reversed CH2-linked C-glycosides (ACS-Fall 2026) - "However, despite recent work illustrating the value of substituting non-anomeric C–O bonds for C–C bonds, highlighted by the recent FDA approval of the reversed glycoside sotagliflozin, methods for modifying non-anomeric positions are comparatively limited...Exploration of the electrophile scope showed generality across a variety of aryl and heteroaryl bromides, including challenging pyridyl and unprotected indole electrophiles as well as four tripeptides containing a (hetero)aryl bromide-functionalized amino acid residue. Taken together, this work illustrates the viability of non-anomeric glycoboranes as intermediates in the synthesis of functionalized glycosides."

QbD-Assisted RP-HPLC Method Development and Validation for the Quantification of Sotagliflozin With LC-MS/MS Characterization of Its Degradation Products and Greenness Assessment Using AGREE and MoGAPI. (PubMed, Biomed Chromatogr) - "LC-MS/MS enabled identification and structural characterization of four major degradation products. Greenness assessment using AGREE and MoGAPI tools yielded scores of 0.89 and 91, respectively, confirming the method's eco-friendly nature for routine pharmaceutical analysis."

Journal • Cardiovascular • Diabetes • Metabolic Disorders

Mitigating DKA in Type 1 Diabetes for Safe Use of SGLT Inhibitors Using Dual Continuous Ketone and Glucose Monitoring. (clinicaltrials.gov) - P2 | N=80 | Not yet recruiting | Sponsor: HealthPartners Institute | Initiation date: Jun 2026 ➔ Sep 2026

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

Dual inhibition of SGLT 1 and 2 by sotagliflozin alleviates intracellular sodium overload and improves cardiometabolic remodelling in uraemic cardiomyopathy. (PubMed, Cardiovasc Res) - "Myocardial Naᵢ overload emerges as an early and potentially modifiable feature of uraemic cardiomyopathy. Dual SGLT1/2 inhibition with SOTA directly lowers Naᵢ and improves cardiac metabolic homeostasis, supporting Naᵢ as a mechanistically relevant and potentially targetable pathway in CKD-related cardiac remodelling."

Journal • Cardiomyopathy • Cardiovascular • Chronic Kidney Disease • Metabolic Disorders • Nephrology • Renal Disease

Dual SGLT1/2 inhibition with sotagliflozin improves cardiac function and metabolism in type 2 diabetic mice. (PubMed, NPJ Metab Health Dis) - "In the heart, SOTA partially restored glycolytic intermediates and improved bioenergetics, whereas systemic metabolic abnormalities largely persisted. These findings suggest dual SGLT1/2 inhibition induces selective cardiac metabolic remodelling in diabetic cardiomyopathy independent of global metabolic correction."

Journal • Preclinical • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Diabetes • Genetic Disorders • Heart Failure • Metabolic Disorders • Obesity • Reperfusion Injury • Type 2 Diabetes Mellitus

SONATA-HCM: A Study to Evaluate the Efficacy and Safety of Sotagliflozin in Symptomatic Obstructive and Non-obstructive Hypertrophic Cardiomyopathy (clinicaltrials.gov) - P3 | N=500 | Active, not recruiting | Sponsor: Lexicon Pharmaceuticals | Recruiting ➔ Active, not recruiting

Enrollment closed • Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy • Non-obstructive Hypertrophic Cardiomyopathy • Obstructive Hypertrophic Cardiomyopathy

Sodium-glucose Cotransporter-2 Inhibitors and Risk of Venous Thromboembolism: A Systematic Review and Meta-analysis (ISTH 2026) - "Among individual agents, empagliflozin was associated with lower VTE risk (OR, 0.62 [95% CI: 0.58-0.90]), whereas estimates for dapagliflozin, canagliflozin, ertugliflozin, and sotagliflozin did not differ significantly from placebo. Additional studies are warranted to clarify which patient populations may derive the greatest benefit. Table or Figure Upload (1) Forest plot summarizing the association of SGLT2 inhibitors and overall total venous thromboembolism events Page 2 Table or Figure Upload (2) Forest plot summarizing the association of individual SGLT2 inhibitors and overall total venous thromboembolism events DOI*10.1016/j.rpth.2026.103717"

Retrospective data • Review • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Diabetes • Heart Failure • Hematological Disorders • Metabolic Disorders • Nephrology • Renal Disease • Respiratory Diseases • Type 2 Diabetes Mellitus • Venous Thromboembolism

Efficacy and Safety of SGLT2 Inhibitors and Sotagliflozin in Heart Failure: A Systematic Review and Meta-Analysis of 59 Randomized Controlled Trials. (PubMed, Cureus) - "Results were directionally consistent across 13 sensitivity scenarios and five alternative statistical models. SGLT2 inhibitors reduce HFH, CV death, the composite endpoint, and serious adverse events with moderate-to-high certainty; the all-cause mortality reduction is of low certainty and sensitive to publication bias."

Journal • Retrospective data • Review • Acute Kidney Injury • Cardiovascular • Congestive Heart Failure • Heart Failure • Hypotension • Infectious Disease • Metabolic Disorders • Nephrology • Renal Disease

Load-Dependent Effects of Sodium Glucose Co-Transporter Inhibitors on Work in Human Hypertrophic Cardiomyopathy Living Myocardial Slices. (PubMed, bioRxiv) - "Following baseline measurements, slices were loaded with drug (isoproterenol, mavacamten, sotagliflozin, or empagliflozin) or vehicle (DMSO) and work loop analysis was repeated, allowing each slice to serve as its own control. Our LMS platform enables assessment of myocardial mechanics across controlled loading conditions and is an ideal platform to rigorously phenotype human myocardial tissue and interrogate direct effects of pharmacologic intervention. We demonstrate that SGLTi and ketones have distinct and discordant effects on human myocardial contractility."

Journal • Cardiomyopathy • Cardiovascular • Hypertension • Hypertrophic Cardiomyopathy

Direct Antiplatelet Effects of the Dual Sodium Glucose Transporter Inhibitor (SGLT1 and SGLT2) Sotagliflozin Support its Use in Prevention of Thrombosis (ISTH 2026) - "Aims To determine the cardiovascular protective effect of sotagliflozin compared to the SGLT2-selective inhibitor, empagliflozin, by evaluating effects on platelet activation and thrombus formation. This study is the first to demonstrate the potential therapeutic benefit of sotagliflozin for prevention of thrombosis. DOI*10.1016/j.rpth.2026.105249"

Cardiovascular • Diabetes • Hematological Disorders • Metabolic Disorders • Myocardial Infarction • Thrombosis • Type 2 Diabetes Mellitus

Sotagliflozin pretreatment attenuates acute LPS-induced depression-like behavioral abnormalities and modulates the gut microbiota-immune-brain axis. (PubMed, Psychopharmacology (Berl)) - "SOTA pretreatment attenuates acute LPS-induced depression-like behavioral abnormalities in association with reduced systemic inflammation, blunted synaptic protein loss, and altered gut microbiota profiles. Dual SGLT1/2 inhibition warrants further investigation in inflammation-associated mood disorders."

Journal • CNS Disorders • Depression • Inflammation • Mood Disorders • Psychiatry • IL6 • TNFA

Relationship Between hsCRP, Glycaemic Control and Response to Sotagliflozin in Type 1 Diabetes: A Post Hoc Analysis of the inTandem3 Trial. (PubMed, Diabetes Obes Metab) - No abstract available

Journal • Retrospective data • Cardiovascular • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus • CRP

Sotagliflozin improves cognitive deficits and attenuates neuroinflammation of Alzheimer's disease. (PubMed, Neurotherapeutics) - "Our findings suggest that Sota improved cognitive impairment and attenuates neuroinflammation in AD. Sota may be a promising candidate for the treatment of AD."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Diabetes • Inflammation • Metabolic Disorders