Sotagliflozin Efficacy in Nondiabetic HFpEF: Juan Badimon, PhD

Sodium-glucose cotransporter (SGLT) inhibitors have established themselves as foundational therapy for heart failure, but confirming their mechanism-agnostic efficacy across all patient groups is important, explained Juan Badimon, PhD, FACC, FAHA, professor of medicine and director of the Atherothrombosis Research Unit at The Mount Sinai School of Medicine’s Cardiovascular Institute.

At the 2025 American Heart Association Scientific Sessions, Badimon presented results from the SOTA-P-CARDIA trial, a dedicated, randomized, double-blind, placebo-controlled study, which was designed to test the dual SGLT1/2 inhibitor sotagliflozin (Inpefa; Lexicon Pharmaceuticals) in patients with heart failure with preserved ejection fraction (HFpEF) who do not have type 2 diabetes. The central rationale for this focused, randomized design was to ensure similarities between the study groups and standardize concomitant therapy.

Sotagliflozin was approved by the FDA more than 2 years ago for patients with heart failure regardless of their diabetic status,¹ but these new results demonstrate the clinical benefits for patients with preserved ejection fraction without diabetes, Badimon said in a press release.²

SOTA-P-CARDIA enrolled 50 patients (25 per arm) and set its primary end point as the change in plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) at 12 weeks, a key biomarker of cardiac stress. Secondary end points included changes in left ventricular function, quality of life, and exercise capacity based on the 6-minute walking test.

These data significantly broaden the potential treatment landscape, reinforcing the view that HFpEF is not solely a complication of diabetes. Badimon concluded that the data needs “to be corroborated in a larger clinical setting” to solidify its position as a standard of care regardless of a patient's diabetic status.

Reference

1. Inserro A. FDA approves sotagliflozin, a dual SGLT1/2 inhibitor, for full range of heart failure. AJMC®. May 27, 2023. Accessed November 10, 2025. https://www.ajmc.com/view/fda-sotagliflozin-a-dual-sglt1-2-inhibitor-for-full-range-of-heart-failure

2. 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. News release. Lexicon Pharmaceuticals. November 8, 2025. Accessed November 10, 2025. https://investors.lexpharma.com/news-releases/news-release-details/clinical-data-demonstrating-efficacy-sotagliflozin-preserved