Inpefa (sotagliflozin) / Lexicon Pharma - LARVOL DELTA

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

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

Comparison of Antiplatelet Effects of Sotagliflozin to FDA-approved Antiplatelet Drugs (clinicaltrials.gov) - P1 | N=20 | Not yet recruiting | Sponsor: University of Michigan

New P1 trial

Efficacy and safety of sotagliflozin in patients with symptomatic obstructive and non-obstructive hypertrophic cardiomyopathy (SONATA-HCM): study design (HEART FAILURE 2025) - No abstract available

Clinical • Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy • Non-obstructive Hypertrophic Cardiomyopathy • Obstructive Hypertrophic Cardiomyopathy

Therapeutic Potential of Sotagliflozin in Animal Models of Non-alcoholic Fatty Liver Disease with and without Diabetes. (PubMed, Drug Res (Stuttg)) - "Both the treatments improved plasma fibroblast growth factor 21, hepatic interlukin-6, glucose tolerance, steatosis and mitigated fat pad weight, but their combination did not show additional benefit. However, combination treatment demonstrated added benefit in modulating NAFLD activity score, liver enzymes, glycogenated hepatic nuclei, plasma glucose and active GLP-1 levels.Study underscores sotagliflozin's potential to mitigate NAFLD and highlights the benefit of combining it with linagliptin in hyperglycemic NASH model, which showed limited efficacy in normoglycemic FLD mice."

Journal • Preclinical • Diabetes • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • FGF21

Sotagliflozin in Refractory Hypomagnesemia. (PubMed, Kidney Int Rep) - No abstract available

Journal

Incremental benefits of combined inhibition of SGLT1 and SGLT2 with sotagliflozin. (PubMed, Prog Cardiovasc Dis) - No abstract available

Journal

Sotagliflozin provides additional benefits for high-fat diet-induced cardiac inflammatory injury by extra inhibiting P38MAPK and JNK. (PubMed, Int Immunopharmacol) - "These findings suggest that the cardioprotective effects of sotagliflozin against obesity-related cardiomyopathy are mediated through multi-target inhibition of P38MAPK and JNK pathways. Targeting inflammatory signaling pathways while managing cardiovascular risk factors may represent a promising therapeutic strategy for obesity-associated cardiovascular diseases."

Journal • Cardiomyopathy • Cardiovascular • Diabetes • Dyslipidemia • Genetic Disorders • Hypertension • Inflammation • Metabolic Disorders • Obesity

Sotagliflozin Added to Insulin Reduces the Risk of Clinically Important Hypoglycemic Events in Adults with Type 1 Diabetes Regardless of Kidney Function (ADA 2025) - "Available on Friday, June 13, 2025 at 08:00am CDT."

Clinical • Diabetes • Hypoglycemia • Metabolic Disorders • 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) - "Available on Friday, June 13, 2025 at 08:00am CDT."

Retrospective data • Diabetes • Metabolic Disorders

EFFECT OF SGLT2I ON LEFT VENTRICULAR EJECTION FRACTION AND INFARCT SIZE IN ANIMAL MODELS OF MYOCARDIAL INFARCTION: SYSTEMATIC LITERATURE REVIEW AND META-ANALYSIS - Claudia Baez-Diaz (ACC 2025) - "We performed subgroup analysis looking at the influence of each individual gliflozin, diabetic status of the subjects (Y/N) and animal species (rodents versus swine). Eligible studies used empagliflozin, dapagliflozin, canagliflozin, ertugliflozin or sotagliflozin. The use of SGLT2i in animal models of MI and IR seems to have a beneficial effect on cardiac function irrespectively of the SGLT2i used as reflected by an improvement in EF, but dapagliflozin could be more effective in decreasing infarct size than empagliflozin in the experimental setting."

Preclinical • Retrospective data • Review • Cardiovascular • Congestive Heart Failure • Heart Failure • Myocardial Infarction • Reperfusion Injury

Insightful Perspectives on Sodium-glucose Co-transporter 2 Inhibitors: Navigating Safety Updates and Beyond. (PubMed, Curr Drug Res Rev) - "This class includes five drugs, including canagliflozin, ertugliflozin, sotagliflozin, dapagliflozin, and empagliflozin. In general, SLGT2 inhibitors are an efficient diabetes treatment with strong cardiovascular and renal protection and a favourable safety overview. This review sought to summarise the safety overview of commercially available SGLT2 inhibitors."

Journal • Review • Cardiovascular • Congestive Heart Failure • Diabetes • Heart Failure • Hypoglycemia • Infectious Disease • Metabolic Disorders • Musculoskeletal Diseases • Nephrology • Orthopedics • Type 2 Diabetes Mellitus

EVALUATING THE COST-EFFECTIVENESS OF SOTAGLIFLOZIN IN HEART FAILURE PATIENTS WITH PRESERVED AND REDUCED EJECTION FRACTIONS: INSIGHTS FROM THE SOLOIST-WHF TRIAL - Zugui Zhang (ACC 2025) - "Sotagliflozin, priced at $434/month, is a clinically and economically favorable option for patients with diabetes and recent heart failure exacerbations, particularly benefiting HFpEF."

Clinical • Cost effectiveness • HEOR • Cardiovascular • Congestive Heart Failure • Diabetes • Heart Failure • Metabolic Disorders • Type 2 Diabetes Mellitus

SOTAGLIFLOZIN, A DUAL SGLT1/2 INHIBITOR, UNLIKE THE SELECTIVE SGLT2 INHIBITOR EMPAGLIFLOZIN, INHIBITS HUMAN PLATELET ACTIVATION AND IN VIVO THROMBUS FORMATION - Livia Stanger (ACC 2025) - "SOTA inhibits platelet activation by targeting SGLT1 and SGLT2, while EMPA is highly selective for SGLT2. SOTA, but not EMPA, was shown to significantly inhibit platelet activation and thrombosis. The findings presented here provide insight into the potential mechanism by which SOTA reduces stroke and MI in patients with T2DM and CKD and provides a basis for further exploration into the role of SOTA in cardiovascular protection for patients at risk for ischemic events."

Preclinical • Chronic Kidney Disease • Diabetes • Hematological Disorders • Metabolic Disorders • Myocardial Infarction • Nephrology • Renal Disease • Thrombosis • Type 2 Diabetes Mellitus

Effect of Hypoglycemic Drugs on Patients with Heart Failure with or without T2DM: A Bayesian Network Meta-analysis. (PubMed, Rev Cardiovasc Med) - "Sotagliflozin was the most effective in reducing the risk of re-admission due to HF and all-cause death, with a cumulative probability of 0.84 and 0.83, respectively. Liraglutide reduced the risk of cardiovascular death in HF patients with a cumulative probability of 0.97 and had the best efficacy in reducing NTpro-BNP levels with a cumulative probability of 0.69. Empagliflozin was best in improving LVEF in HF patients, with a cumulative probability of 0.69...However, due to the small number of articles in this study, our results must be treated cautiously. Subsequently, there is an urgent need for more high-quality studies to validate our findings."

Journal • Retrospective data • Review • Cardiovascular • Congestive Heart Failure • Diabetes • Heart Failure • Metabolic Disorders • Type 2 Diabetes Mellitus • NPPB

Economic impact of sotagliflozin among patients with heart failure and type 2 diabetes: Budget impact analysis from the US payer perspective. (PubMed, J Manag Care Spec Pharm) - "Breakeven rebate rates ranged between 31.5% and 79.4%. Although sotagliflozin increases pharmacy costs for recently hospitalized HF patients with T2D, approximately 21%-68% of pharmacy costs were offset from reduced rehospitalization and ED visits."

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

Effects of sotagliflozin on kidney and cardiac outcome in a hypertensive model of subtotal nephrectomy in male mice. (PubMed, Physiol Rep) - "Sotagliflozin, however, did not improve markers of kidney injury, inflammation, fibrosis, albuminuria, and plasma FGF23, or signs of cardiac overload, fibrosis, or impaired function. Limited sotagliflozin responsiveness may relate to short treatment time, limited metabolic benefits in nondiabetic setting and/or the model's dominant angiotensin II-driven effects/hypertension."

Journal • Preclinical • Cardiovascular • Chronic Kidney Disease • Fibrosis • Hypertension • Immunology • Inflammation • Metabolic Disorders • Nephrology • Renal Disease • Type 2 Diabetes Mellitus • FGF23

SOTATHROMBUS: Antithrombotic Activities of Sotagliflozin Vs. Empagliflozin (clinicaltrials.gov) - P4 | N=16 | Recruiting | Sponsor: Icahn School of Medicine at Mount Sinai | Not yet recruiting ➔ Recruiting

Enrollment open • Cardiovascular • Congestive Heart Failure • Hematological Disorders • Thrombosis

SOTAGLIFLOZIN IMPROVES TIME IN RANGE (TIR) IN PATIENTS WITH TYPE 1 DIABETES AND CHRONIC KIDNEY DISEASE (ATTD 2025) - "The improvement in TIR was associated with a significant reduction in TAR without an increase in TBR. Conclusions In patients with T1D and CKD, treatment with sotagliflozin 400 mg significantly improved TIR by more than 4 hours at week 24."

Clinical • Chronic Kidney Disease • Diabetes • Metabolic Disorders • Nephrology • Renal Disease • Type 1 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

Lexicon Pharmaceuticals Reports Fourth Quarter and Full Year 2024 Financial Results and Provides Business Updates (GlobeNewswire) - "Pilavapadin (LX9211) for DPNP: The Company is moving toward an end of Phase 2 meeting with FDA and targeting initiation of U.S. and ex-U.S. Phase 3 trials in DPNP in 2025, while selecting a future medical meeting for release of additional clinical data later this year....LX9851 for Obesity and Associated Cardiometabolic Disorders: LX9851 is progressing in IND-enabling studies and on track for a 2025 investigational new drug (IND) application submission. Zynquista (sotagliflozin): Discontinued preparation for potential Zynquista launch in type 1 diabetes following receipt of complete response letter from FDA."

Discontinued • IND • New P3 trial • P3 data • Diabetic Neuropathy • Obesity • Peripheral Neuropathic Pain • Type 1 Diabetes Mellitus

Published Data in The Lancet Diabetes & Endocrinology Highlights Unique Efficacy Benefits of Sotagliflozin to Reduce Major Adverse Cardiovascular Events (MACE) (GlobeNewswire) - P3 | N=10,584 | SCORED (NCT03315143) | Sponsor: Lexicon Pharmaceuticals | "The findings from the study...concluded that the ischemic benefit of sotagliflozin on both heart attack (myocardial infarction, or MI), and stroke reduction has not been shown by other SGLT inhibitors. The researchers note that sotagliflozin reduced major adverse cardiovascular events (MACE), MI, and stroke among patients with type 2 diabetes (T2D), chronic kidney disease (CKD), and high cardiovascular (CV) risk...Patients in the sotagliflozin group had a lower rate of MACE outcomes (4.8 events per 100 person-years [p-y]) compared with the placebo group (6.3 events per 100 p-y) (hazard ratio [HR]: 0.77; 95% confidence interval [CI]: 0.65-0.91; P=0.002). MACE benefit was consistent across pre-specified subgroups. Additionally, sotagliflozin reduced the rate of MI (1.8 events per 100 p-y) compared with the placebo group (2.7 events per 100 p-y) (HR: 0.68; 95% CI: 0.52-0.89; P=0.004)..."

P3 data • Cardiovascular • Chronic Kidney Disease • Type 2 Diabetes Mellitus

Effect of sotagliflozin on major adverse cardiovascular events: a prespecified secondary analysis of the SCORED randomised trial. (PubMed, Lancet Diabetes Endocrinol) - P3 | "Sotagliflozin reduced MACE, with independent reductions in myocardial infarction and stroke, among patients with type 2 diabetes, chronic kidney disease, and additional cardiovascular risk. The ischaemic benefit on both myocardial infarction and stroke has not been previously observed with other SGLT inhibitors and warrants investigation of combined SGLT1 and SGLT2 inhibition as a possible underlying mechanism."

Adverse events • Journal • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Diabetes • Heart Failure • Metabolic Disorders • Myocardial Infarction • Nephrology • Renal Disease • Type 2 Diabetes Mellitus

SOPHIST: Sotagliflozin in Patients with Heart Failure Symptoms and Type 1 Diabetes (clinicaltrials.gov) - P2 | N=320 | Recruiting | Sponsor: University of Dundee | Not yet recruiting ➔ Recruiting

Enrollment open • Cardiovascular • Congestive Heart Failure • Diabetes • Heart Failure • Metabolic Disorders • Type 1 Diabetes Mellitus