Lexicon Pharmaceuticals announced new clinical data demonstrating the efficacy of sotagliflozin in heart failure patients with preserved ejection fraction (HFpEF) without diabetes, presented at the American Heart Association Annual Scientific Sessions 2025. The SOTA P CARDIA trial represents the first study to show clinical benefits of sotagliflozin specifically in this patient population, addressing a significant unmet medical need.
Study Design and Patient Population
The SOTA P CARDIA trial was a prospective, randomized, double-blind, placebo-controlled study conducted under the direction of Dr. Juan J Badimon, PhD, FACC, FAHA, director of the Atherothrombosis Research Unit and professor of Medicine/Cardiology at Mount Sinai Medical Center in New York City. The study exclusively enrolled patients with HFpEF, described as the most rapidly increasing form of heart failure.
The trial enrolled 88 participants who were racially diverse and 70 percent female. Patients received either sotagliflozin or placebo for six months, with comparisons made between groups during and after treatment completion. The study's objective was to evaluate sotagliflozin's effects on cardiac functional and structural measures, including left ventricular mass, diastolic function, standard six-minute walk test, and Kansas City Cardiomyopathy Questionnaire (KCCQ) scores.
Primary Clinical Outcomes
Treatment with sotagliflozin resulted in statistically significant improvements across multiple key endpoints. Patients demonstrated significant improvements in left ventricular mass, diastolic function, capacity for a six-minute walk test, and KCCQ measurements. While peak VO2 improvement did not achieve statistical significance, there was a notable improvement after sotagliflozin treatment.
"The benefits observed with sotagliflozin treatment in the study include significant improvements in cardiac structure and function, symptom relief and, most importantly, quality of life and functional capacity," said Dr. Badimon. "Although sotagliflozin was approved more than two years ago for heart failure patients with or without diabetes, our study is the first to demonstrate important clinical benefits for patients with preserved ejection fraction without diabetes."
Clinical Significance and Disease Burden
According to the American College of Cardiology, nearly 6.7 million Americans have heart failure, with more than half having preserved ejection fraction. This condition frequently leads to hospitalizations and carries a one-year mortality risk of approximately 25 percent, highlighting the critical need for effective therapeutic interventions.
Craig Granowitz, M.D., Ph.D., Lexicon's senior vice president and chief medical officer, emphasized the broader therapeutic potential: "When you combine these study results with previously reported data on reductions among patients treated with sotagliflozin in the risks for MACE and rehospitalization following previous hospitalization for acute heart failure events, the potential for sotagliflozin to be considered a different class of medication starts to come into focus."
Drug Mechanism and Development
Sotagliflozin is an oral inhibitor of two proteins responsible for glucose regulation: sodium-glucose cotransporter types 2 and 1 (SGLT2 and SGLT1). SGLT2 handles glucose and sodium reabsorption by the kidney, while SGLT1 manages glucose and sodium absorption in the gastrointestinal tract. The drug was discovered using Lexicon's unique genomics-based approach to target identification.
The compound has been extensively studied across multiple patient populations, including heart failure, diabetes, and chronic kidney disease, with clinical studies involving approximately 20,000 patients. Sotagliflozin is currently under investigation for hypertrophic cardiomyopathy (HCM), expanding its potential cardiac applications beyond heart failure.
