Inpefa (sotagliflozin) / Lexicon Pharma - LARVOL DELTA

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

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

Targeting Metabolic Dysfunction and Inflammation with Sotagliflozin Reverses Diastolic Dysfunction in Experimental HFpEF. (PubMed, bioRxiv) - "Dual SGLT1/2 inhibition with sotagliflozin exerts coordinated cardiometabolic benefits in experimental HFpEF through metabolic reprogramming toward enhanced lipid utilization and suppression of cardiac and systemic inflammation. These findings establish that sotagliflozin targets the intertwined metabolic-inflammatory axis central to HFpEF pathogenesis, providing mechanistic insight into the therapeutic efficacy of dual SGLT inhibition in cardiometabolic heart failure."

Journal • Cardiovascular • Congestive Heart Failure • Fibrosis • Genetic Disorders • Heart Failure • Hypertension • Immunology • Inflammation • Metabolic Disorders • Obesity • CCR2 • IL1B

Impact of diabetes on the effects of SGLT2 inhibitors on kidney outcomes: An updated drug/dose-dependent meta-analysis. (PubMed, Clin Nephrol) - "SGLT2 inhibitors confer renal protection in both diabetic and non-diabetic populations, supporting their use in CKD management across a broad spectrum of patients. However, careful drug selection is warranted in diabetic patients at risk for DKA."

Journal • Retrospective data • Acute Kidney Injury • Cardiovascular • Chronic Kidney Disease • Diabetes • Metabolic Disorders • Nephrology • Renal Disease

Association of SGLT2 Inhibitors with Reduced Mortality and Improved Clinical Outcomes in Patients with Cancer and CKD: A Real-World Propensity-Matched Analysis (KIDNEY WEEK 2025) - "Patients prescribed SGLT2i (dapagliflozin, empagliflozin, canagliflozin, ertugliflozin, sotagliflozin) were matched 1:1 to controls without SGLT2i. Conclusion SGLT2i use in cancer patients with CKD is associated with substantial reductions in mortality and major adverse renal, cardiovascular, and healthcare utilization outcomes, but is linked to a higher hazard of DKA. These findings support SGLT2i therapy as a promising strategy in this vulnerable population, with appropriate DKA risk monitoring."

Clinical • Clinical data • Real-world • Real-world evidence • Acute Kidney Injury • Anemia • Chronic Kidney Disease • Congestive Heart Failure • Diabetic Nephropathy • Fatigue • Heart Failure • Metabolic Disorders • Myocardial Infarction • Nephrology • Oncology • Renal Disease

Dual SGLT1/2 Inhibition Attenuates Salt-Sensitive Hypertension and Kidney Injury More Effectively than SGLT2 Inhibition (KIDNEY WEEK 2025) - "The recent FDA approval of the dual SGLT1/2i sotagliflozin (Sota) for HFpEF and HFrEF underscores the therapeutic potential of SGLT inhibition...Methods Eight-week-old Dahl SS rats of both sexes were treated with dapagliflozin (Dapa; 2 mg/kg/day) or Sota (30 mg/kg/day) for 3 weeks while maintained on a high salt diet (4% NaCl)...Conclusion Dual SGLT1/2 inhibition more effectively reduces SS HTN and renal injury compared to SGLT2 inhibition. These findings suggest distinct and possibly additive mechanisms, warranting further investigation of underlying molecular pathways."

Cardiovascular • Diabetes • Hypertension • Metabolic Disorders • Renal Disease • Type 2 Diabetes Mellitus

Cardiovascular Risk Prediction Modelling with Sotagliflozin in Type 1 Diabetes: Analysis of inTandem 1-3 Trials (KIDNEY WEEK 2025) - "Conclusion Sotagliflozin improves predicted CVD risk in T1D participants at low cardiorenal risk. By highlighting the predicted cardiovascular risk benefit in a large low-risk T1D cohort, our findings underline the need to investigate the effect of SGLT inhibitors on hard cardiovascular endpoints in T1D, especially in high-risk cohorts."

Cardiovascular • Chronic Kidney Disease • Diabetes • Metabolic Disorders • Nephrology • Renal Disease • Type 1 Diabetes Mellitus • Type 2 Diabetes Mellitus

Add-On SGLT2 Inhibitors: New Era of Diuresis in Acute Heart Failure (KIDNEY WEEK 2025) - "The add-on agents were Dapagliflozin (6 trials), Empagliflozin (4 trials), and Sotagliflozin (1 trial). Conclusion While the current guidelines of AHF recommend intensifying LD therapy prior to adding a second agent to enhance the decongestion process, there is no consensus on an optimal diuretic strategy. This study shows that 1) there is significant inconsistency in reporting of the decongestion markers and their timing in the studies of AHF, 2) while adding SGLT2 inhibitors to LD seems to be an intriguing option, a reliable comparison of their efficacy is challenging, and 3) these agents do not seem to increase the rate of AKI despite efficient decongestion in AHF."

Acute Kidney Injury • Cardiovascular • Congestive Heart Failure • Heart Failure • Nephrology • Renal Disease

Comparison of the Anti-Platelet and Anti-Thrombotic Effects of the Dual SGLT1/2 Inhibitor Sotagliflozin to the Relatively Selective SGLT2 Inhibitor Empagliflozin (ASH 2024) - "The overwhelming majority of the anti-thrombotic effects of SOTA appear to be due to SGLT1 inhibition. While further investigation is warranted, our results underscore the potential of SOTA to reduce cardiovascular outcomes in patients with T2DM and CKD at high risk for thrombotic events."

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

SOTA-P-CARDIA Trial (ATRU-V). A Randomized Trial of Sotagliflozin in HFpEF patients without diabetes. (AHA 2025) - P4 | "Additionally, Peak VO2 improved in the sotagliflozin group, but without reaching statistical significance. In conclusion, our data support the potential use of sotagliflozin in the management of HFpEF patients without diabetes, expanding the therapeutic benefit of dual SGLT1/2 inhibition beyond the diabetic population."

Clinical • Cardiovascular • Congestive Heart Failure • Diabetes • Heart Failure • Metabolic Disorders

Effects on major adverse cardiovascular events in persons treated with sotagliflozin: Prespecified pooled analyses of the Phase 3 type 2 diabetes program (AHA 2025) - "Of these, 2,904 participants were treated with sotagliflozin (200 or 400 mg QD), while 2,196 were in an All-Comparators group (pooling placebo, empagliflozin, and glimepiride). Two independent data sources (9 cardiometabolic Phase 3 studies and the SCORED CV outcomes trial), including approximately 15,000 participants, support a reduction in MACE with sotagliflozin in a broad group of persons with T2D, and reinforce the role of sotagliflozin in reducing atherosclerotic cardiovascular risk."

Adverse events • P3 data • Atherosclerosis • Cardiovascular • Chronic Kidney Disease • Diabetes • Metabolic Disorders • Myocardial Infarction • Nephrology • Renal Disease • Type 2 Diabetes Mellitus

SGLT2 Inhibitors in Rheumatic Heart Disease (AHA 2025) - "Patients with documented exposure to SGLT2i (empagliflozin, dapagliflozin, or sotagliflozin) formed the treatment group, while those unexposed to any SGLT2i comprised the control group. However, SGLT2i users experienced a higher incidence of acute kidney injury (AKI) (RR 1.483, 95% CI: 1.396–1.575, p < 0.001; HR 1.382, 95% CI: 1.299–1.470, p < 0.001) atrial fibrillation (RR 1.460, 95% CI: 1.365–1.562, p < 0.001; HR 1.352, 95% CI: 1.262–1.449, p < 0.001) and increased risk for emergency department visits (RR 1.380, 95% CI: 1.289–1.477, p < 0.001; HR 1.275, 95% CI: 1.188–1.367, p < 0.001).ConclusionIn this study, SGLT2i use in patients with RHD was associated with a significant reduction in all-cause mortality but increased risk of AKI, atrial fibrillation, and ED visits. These findings suggest that while SGLT2 inhibitors may offer mortality benefit in RHD, they may carry unique risks in this structurally distinct population, highlighting the need for..."

Acute Kidney Injury • Atrial Fibrillation • Cardiovascular • Heart Failure • Nephrology • Renal Disease

Sotagliflozin Enhances Left Ventricular Function and Myocardial Perfusion in Chronic Myocardial Ischemia Through Metabolic and Redox Remodeling (AHA 2025) - "Sotagliflozin treatment improved left ventricular function, myocardial perfusion, and diastolic relaxation, likely through reduced oxidative stress and myocardial fibrosis, improved nitric oxide coupling, enhanced insulin signaling, and favorable metabolic shifts. This study suggests a potential role for sotagliflozin as a cardioprotective therapy in patients with IHD beyond current treatment strategies."

Cardiovascular • Coronary Artery Disease • Diabetes • Fibrosis • Heart Failure • Immunology • Metabolic Disorders • Myocardial Ischemia • Nephrology • Renal Disease • SLC2A4

Dual SGLT1 and 2 Inhibition with Sotagliflozin Ameliorates Adverse Cardiac Remodeling and Diastolic Dysfunction in Mice with HCM Due to Tropomyosin E180G Mutation (AHA 2025) - "Dual SGLT1 and 2 inhibition with Sota attenuated myocardial hypertrophy, diastolic dysfunction, SERCA oxidation and fibrosis in E180G HCM mice. Mitigation of SERCA oxidation and fibrosis by Sota may contribute to improved diastolic function. The attenuation of SERCA oxidation further indicates that Sota decreased oxidative stress, which is a stimulus for myocardial SERCA dysfunction, hypertrophy and fibrosis."

Preclinical • Cardiomyopathy • Cardiovascular • Fibrosis • Hypertrophic Cardiomyopathy • Immunology • Non-obstructive Hypertrophic Cardiomyopathy

Impact of sotagliflozin on glomerular hyperfiltration in people with type 1 diabetes: A post hoc analysis of the inTandem3 trial. (PubMed, Diabetes Obes Metab) - No abstract available

Journal • Retrospective data • Diabetes • Metabolic Disorders • Nephrology • Renal Disease • Type 1 Diabetes Mellitus

Resolution sequence stratigraphic division of the Da2 member in the Yanji Basin based on INPEFA and Milankovitch cycles. (PubMed, Sci Rep) - "Finally, The Da2 sequence is subdivided into 1 long-term, 6 mid-term, and 16 short-term base level cycles, based on which a sequence stratigraphic division scheme is proposed. Based on this, a high-resolution stratigraphic framework is established, which provides accurate geological basis for subsequent comprehensive reservoir evaluation and sand body prediction."

Journal

Comparison of the renal outcomes of novel antidiabetic agents in patients with type 2 diabetes with chronic kidney disease: A systematic review and network meta-analysis of randomized controlled trials. (PubMed, Diabetes Obes Metab) - "In patients with T2DM and CKD, SGLT2 inhibitors provide the most consistent renal protection, while GLP-1 receptor agonists offer additional but variable benefits. Dapagliflozin showed the greatest efficacy, and canagliflozin most strongly reduced albuminuria, highlighting meaningful heterogeneity across agents. DPP-4 inhibitors conferred no renal benefit. Overall, evidence from placebo-controlled trials was robust, whereas certainty was lower for indirect estimates, highlighting the need for drug-specific evaluation in clinical practice."

Journal • Retrospective data • Chronic Kidney Disease • Diabetes • Diabetic Nephropathy • Metabolic Disorders • Nephrology • Renal Disease • Type 2 Diabetes Mellitus

Authors' Reply: Further Considerations on the Clinical Evaluation of Sotagliflozin in Type 1 Diabetes with CKD. (PubMed, J Am Soc Nephrol) - No abstract available

Journal • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

Further Considerations on the Clinical Evaluation of Sotagliflozin in Type 1 Diabetes with CKD. (PubMed, J Am Soc Nephrol) - No abstract available

Journal • Chronic Kidney Disease • Diabetes • Metabolic Disorders • Nephrology • Renal Disease • Type 1 Diabetes Mellitus

CKM For Safe Use of SGLT2i in Type 1 Diabetes (clinicaltrials.gov) - P3 | N=52 | Not yet recruiting | Sponsor: University of California, San Diego

New P3 trial • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

Unveiling The Hidden Risks Of Sotagliflozin: A Nationwide Pharmacovigilance Analysis Of Adverse Events From The FDA Reporting System (HFSA 2025) - "In this pharmacovigilance analysis, sotagliflozin's safety profile included common AEs consistent with its drug class (e.g., dizziness). Notably, older (65-85 years) and male patients showed a higher incidence of reported AEs. Clinicians should remain vigilant when prescribing sotagliflozin to these higher-risk populations, ensuring appropriate monitoring for side effects."

Adverse events • Cardiovascular • Congestive Heart Failure • Diabetes • Gastrointestinal Disorder • Heart Failure • Hypotension • Metabolic Disorders • Pulmonary Disease • Type 1 Diabetes Mellitus

Safety and Tolerability of Sotagliflozin Among Kidney Transplant Recipients. (PubMed, Transplantation) - "Among stable KTRs, sotagliflozin caused an initial decline in eGFR of similar magnitude to patients with chronic kidney disease, with reversibility upon withdrawal. Access to follow-up eGFR measurements did not affect study adherence."

Journal • Chronic Kidney Disease • Infectious Disease • Nephrology • Renal Disease • Transplantation • Urology

Lexicon Pharmaceuticals Announces Update on Submission of Additional Data to U.S. FDA Supporting the Benefit-Risk Profile of Zynquista in Type 1 Diabetes (GlobeNewswire) - "The FDA has informed Lexicon that it requires additional time to review this data and now expects to provide feedback from the September Type D meeting in the fourth quarter, previously anticipated by end of September....Lexicon has been granted a Type D meeting and has submitted data from three ongoing studies of sotagliflozin conducted by the Steno Diabetes Center (STENO1), the Joslin Diabetes Center (SUGARNSALT) and the University of Dundee (SOPHIST) supporting the benefit-risk profile of Zynquista in T1D."

FDA event • Type 1 Diabetes Mellitus

SGLT2 inhibitors for the prevention and treatment of heart failure: A scientific statement of the HFA and the HFAI. (PubMed, ESC Heart Fail) - "Further trials showed efficacy of empagliflozin and dapagliflozin in patients with HF with preserved ejection fraction (HFpEF)...In SOLOIST-WHF and EMPULSE, sotagliflozin (enrolling only patients with T2DM) and empagliflozin, respectively, were beneficial when initiated at the end or soon after an episode of decompensated HF...Potential benefits of SGLT2 inhibitors in further specific conditions (i.e., cardiac amyloidosis, grown-up congenital heart disease and paediatric patients with HF) have been reported in observational studies but need confirmation from prospective trials. This scientific statement summarizes current evidence regarding the effects of SGLT2 inhibitors for the prevention and treatment of HF."

Clinical • Journal • Review • Amyloidosis • Cardiac Amyloidosis • Cardiovascular • Congestive Heart Failure • Diabetes • Heart Failure • Metabolic Disorders • Pediatrics • Type 2 Diabetes Mellitus

Comparison of Antiplatelet Effects of Sotagliflozin to FDA-approved Antiplatelet Drugs (clinicaltrials.gov) - P1 | N=20 | Recruiting | Sponsor: University of Michigan | Not yet recruiting ➔ Recruiting | Trial completion date: May 2026 ➔ Sep 2026 | Trial primary completion date: May 2026 ➔ Sep 2026

Enrollment open • Trial completion date • Trial primary completion date