SOTA-P-CARDIA: Sotagliflozin Exhibits Antithrombotic Effects in Patients with HFpEF, With Juan Badimon, PhD

Sotagliflozin treatment resulted in a statistically significant improvement in left ventricular mass, diastolic function, capacity for the 6-minute walk test, and Kansas City Cardiomyopathy Questionnaire (KCCQ) measurements in patients with heart failure with preserved ejection fraction (HFpEF) without diabetes, according to results from the SOTA-P-CARDIA study.1

These data were presented at the American Heart Association’s Scientific Sessions 2025 in New Orleans, Louisiana, by Juan Badimon, PhD, professor of medicine and director of the atherothrombosis research unit at the Cardiovascular Institute at the Icahn School of Medicine at Mount Sinai. Although the trial reached statistical significance in several measures, it failed to achieve significance in peak VO2 improvement, despite producing a notable improvement after sotagliflozin treatment.1,3

Sotagliflozin is an oral combination SGLT2 and SGLT1 inhibitor, which simultaneously monitors glucose and sodium reabsorption in the kidney and the gastrointestinal tract. It has been studied in patients with HF, diabetes, and chronic kidney disease, and is currently under investigation for hypertrophic cardiomyopathy.1

The previous SOLOIST and SCORED trials investigated sotagliflozin’s efficacy in patients with type 2 diabetes mellitus (T2DM) hospitalized for worsening HF and patients with T2DM and chronic kidney disease, respectively. Both trials achieved their endpoints and saw effects on HF irrespective of left ventricular ejection fraction. However, despite these outcomes, neither trial established sotagliflozin’s mechanism of action.2

The editorial team at HCPLive sat down with Badimon to discuss the implications of these data and next steps for SGLT2 inhibitor research in patients with HF.

“One of the things to take into account is that the SOLOIST and the SCORED trials enrolled exclusively diabetic patients,” Badimon told HCPLive. “So, one of the objectives that we wanted to investigate is whether we could expand the benefits seen in the SOLOIST and SCORED trials to a non-diabetic HFpEF population.”

For enrollment in the SOTA-P-CARDIA study, patients were required to be ambulatory, exhibit no diabetes as confirmed by HbA1c <6.5%, fasting serum glucose <126 mg/dL, and review of concomitant medications and medical history, as well as having a diagnosis of heart failure (HF), LVEF >50%, and being on medical therapy for HF for ≥4 weeks prior to screening. Patients with type 1 and 2 diabetes, acute coronary syndrome or cardiac surgery within the last week, acute decompensated HF or hospitalized HF within 1 month, or who had been receiving SGLT inhibitors 3 months prior to randomization were excluded.2

A total of 88 patients were included, with notable racial diversity and of whom 70% were female. Patients were randomly assigned in blocks of 4 to either sotagliflozin or placebo, administered daily over 6 months. The primary outcome was change in left ventricular mass at 6 months compared to baseline, while secondary endpoints included changes in left ventricular end-systolic volume (LVESV) at 6 months, changes in left ventricular end-diastolic volume (LVEDV) at 6 months, changes in extracellular volume at 6 months, changes in peak oxygen consumption at 6 months, changes in 6-minute walk test results at 6 months, and changes in KCCQ results at 6 months, among other factors.2

Ultimately, investigators found that 6-month satagliflozin administration resulted in improvements in left ventricular mass, diastolic function, 6-minute walk test, and KCCQ measurements. Badimon spoke with HCPLive on the results of the trial, as well as the next steps for sotagliflozin research in patients with HFpEF.

“I think we need to start getting familiar with the dual SGLT-2/SGLT-1 inhibitors because they have similar effects to the specific SGLT-2 inhibitor; they have this effect on reducing atherothrombotic events,” Badimon said. “Theoretically, inhibiting SGL-1 and -2 seems to offer the better choice. But again, we need to be patient; we have more data coming.”

References

1. DeFrancesco L. Clinical Data Demonstrating Efficacy of Sotagliflozin in Preserved Ejection Fraction Heart Failure (HFpEF) without Diabetes Presented at American Heart Association (AHA) Annual Scientific Sessions 2025. Lexicon Pharmaceuticals. November 8, 2025. Accessed November 18, 2025. https://investors.lexpharma.com/news-releases/news-release-details/clinical-data-demonstrating-efficacy-sotagliflozin-preserved

2. Badimon J. Sotagliflozin in Heart Failure with Preserved Ejection Fraction (HFpEF) Patients. ClinicalTrials.gov Identifier: NCT05562063. Updated July 18, 2025. Accessed November 18, 2025. https://www.clinicaltrials.gov/study/NCT05562063

3. Badimon J, Requena JA, Santos-Gallego C, et al. SOTA-P-CARDIA Trial (ATRU-V): A Randomized Trial of Sotagliflozin in HFpEF patients without diabetes. Abstract presented at the American Heart Association’s Scientific Sessions 2025. New Orleans, Louisiana. November 8-10, 2025.