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

Rhea-AI Summary

Lexicon Pharmaceuticals (Nasdaq: LXRX) reported new clinical data presented at AHA 2025 showing sotagliflozin produced statistically significant improvements in cardiac structure, diastolic function, six-minute walk distance and KCCQ scores in patients with preserved ejection fraction heart failure (HFpEF) without diabetes.

The prospective, randomized, double-blind, placebo-controlled SOTA P CARDIA trial enrolled 88 racially diverse participants (70% female) treated for six months. Peak VO2 improved but did not reach statistical significance. The company highlighted these results as the first demonstration of clinical benefit for HFpEF patients without diabetes.

Positive

• Statistically significant improvement in left ventricular mass
• Statistically significant improvement in diastolic function
• Statistically significant improvement in six-minute walk capacity
• Statistically significant improvement in KCCQ quality-of-life scores
• Trial enrolled 88 participants, 70% female

Negative

• Peak VO2 improvement did not reach statistical significance
• Relatively small trial size: 88 participants
• Treatment and follow-up limited to six months

Insights

Cardiovascular Clinical Expert

Randomized trial in 88 HFpEF patients without diabetes showed statistically significant improvements in cardiac structure, function, walk distance and KCCQ over six months.

The trial, "SOTA P CARDIA", randomized 88 racially diverse patients (70 % female) with preserved ejection fraction to sotagliflozin or placebo for six months. Reported statistically significant improvements included left ventricular mass, diastolic function, six‑minute walk distance and KCCQ scores; peak VO2 improved but did not reach statistical significance. These endpoints measure heart structure, filling dynamics, symptoms and health‑related quality of life, which are directly relevant to clinical benefit in HFpEF.

Key dependencies and risks include the small sample size and short treatment duration; the findings are promising but limited to 88 participants and a six‑month follow‑up, so broader reproducibility and durability remain untested. The reported statistical significance across multiple structural and patient‑reported measures strengthens credibility, but the non‑significant peak VO2 and lack of longer‑term outcomes require cautious interpretation.

Concrete items to watch over the next 6–24 months include publication of full data with exact p‑values and effect sizes, any larger confirmatory trials or regulatory filings that reference these results, and subgroup analyses given the 70 % female enrollment; these will determine how broadly the results apply and whether they affect clinical guidance or label language.

Oral presentation highlights sotagliflozin's unique benefits to HFpEF patients in significantly improving cardiac and physical performance, and quality of life

THE WOODLANDS, Texas, Nov. 08, 2025 (GLOBE NEWSWIRE) -- Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX) today announced that new sotagliflozin clinical data was presented at the AHA Annual Scientific Sessions 2025. The data highlighted benefits observed from sotagliflozin treatment in heart failure patients with preserved ejection fraction (HFpEF), and without diabetes, across a range of measures, including cardiac structure and function, quality of life and functional capacity.

Conducted under the direction of Dr. Juan J Badimon, PhD, FACC, FAHA, director, Atherothrombosis Research Unit, professor of Medicine/Cardiology at Mount Sinai Medical Center in New York City, “SOTA P CARDIA: A Randomized Trial of Sotagliflozin in HFpEF Patients without Diabetes” was a prospective, randomized, double-blind, placebo-controlled trial that exclusively enrolled patients with HFpEF, the most rapidly increasing form of heart failure.

The objective of the study was to compare treatment with sotagliflozin to placebo on a number of cardiac functional and structural measures, such as left ventricular mass, diastolic function, standard six-minute walk test, and KCCQ. The study enrolled 88 participants who were racially diverse and 70 percent female. Patients were treated with sotagliflozin or placebo for six months, and comparisons were made between groups during and after completion of treatment.

Treatment with sotagliflozin resulted in statistically significant improvements in left ventricular mass, diastolic function, capacity for a six-minute walk test, and KCCQ measurements. In addition, though peak VO₂ improvement did not achieve statistical significance, there was a notable improvement after treatment with sotagliflozin.

“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.”

According to the American College of Cardiology, nearly 6.7 million Americans have heart failure, more than half with preserved ejection fraction. This condition often leads to frequent hospitalizations and has a one-year risk of death of roughly 25 percent.

“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,” said Craig Granowitz, M.D., Ph.D., Lexicon’s senior vice president and chief medical officer.

Click here and search for “SOTA P CARDIA” to access the study abstract.

About Sotagliflozin 
Discovered using Lexicon’s unique approach to gene science, sotagliflozin is an oral inhibitor of two proteins responsible for glucose regulation known as sodium-glucose cotransporter types 2 and 1 (SGLT2 and SGLT1). SGLT2 is responsible for glucose and sodium reabsorption by the kidney and SGLT1 is responsible for glucose and sodium absorption in the gastrointestinal tract. Sotagliflozin has been studied in multiple patient populations encompassing heart failure, diabetes, and chronic kidney disease in clinical studies involving approximately 20,000 patients. Sotagliflozin is also currently under investigation for another cardiac condition, hypertrophic cardiomyopathy (HCM). 

About Lexicon Pharmaceuticals    
Lexicon is a biopharmaceutical company with a mission of pioneering medicines that transform patients’ lives. Through the Genome5000™ program, Lexicon’s unique genomics target discovery platform, Lexicon scientists studied the role and function of nearly 5,000 genes and identified more than 100 protein targets with significant therapeutic potential in a range of diseases. Through the precise targeting of these proteins, Lexicon is pioneering the discovery and development of innovative medicines to treat disease safely and effectively. Lexicon has a pipeline of promising drug candidates in discovery and clinical and preclinical development in neuropathic pain, HCM, obesity, metabolism and other indications.  For additional information, please visit www.lexpharma.com.

Safe Harbor Statement    
This press release contains “forward-looking statements,” including statements relating to Lexicon’s financial position and long-term outlook on its business, including the commercialization of its approved products and the clinical development of, regulatory filings for, and potential therapeutic and commercial potential of sotagliflozin and its other drug candidates. In addition, this press release also contains forward looking statements relating to Lexicon’s growth and future operating results, discovery, development and commercialization of products, strategic alliances and intellectual property, as well as other matters that are not historical facts or information. All forward-looking statements are based on management’s current assumptions and expectations and involve risks, uncertainties and other important factors, specifically including Lexicon’s ability to meet its capital requirements, successfully commercialize its approved products, successfully conduct preclinical and clinical development and obtain necessary regulatory approvals of its other drug candidates on its anticipated timelines, achieve its operational objectives, obtain patent protection for its discoveries and establish strategic alliances, as well as additional factors relating to manufacturing, intellectual property rights, and the therapeutic or commercial value of its approved products and other drug candidates. Any of these risks, uncertainties and other factors may cause Lexicon’s actual results to be materially different from any future results expressed or implied by such forward-looking statements. Information identifying such important factors is contained under “Risk Factors” in Lexicon’s annual report on Form 10-K for the year ended December 31, 2024, as filed with the Securities and Exchange Commission. Lexicon undertakes no obligation to update or revise any such forward-looking statements, whether as a result of new information, future events or otherwise.    

For Investor and Media Inquiries:   

Lisa DeFrancesco    
Lexicon Pharmaceuticals, Inc.   
lexinvest@lexpharma.com  

FAQ

What did Lexicon announce about sotagliflozin in HFpEF on November 8, 2025 (LXRX)?

Lexicon presented SOTA P CARDIA data showing sotagliflozin produced statistically significant improvements in left ventricular mass, diastolic function, six-minute walk distance and KCCQ in HFpEF patients without diabetes.

How large and how long was the SOTA P CARDIA trial for sotagliflozin (LXRX)?

SOTA P CARDIA enrolled 88 racially diverse participants (70% female) treated with sotagliflozin or placebo for six months.

Did sotagliflozin improve peak VO2 in the HFpEF trial presented at AHA 2025 (LXRX)?

Peak VO2 showed a notable improvement after treatment but did not achieve statistical significance in the trial.

Which clinical measures improved with sotagliflozin in the HFpEF study (LXRX)?

The trial reported statistically significant improvements in left ventricular mass, diastolic function, six-minute walk capacity and KCCQ quality-of-life scores.

Does the SOTA P CARDIA trial show sotagliflozin benefits for HFpEF patients without diabetes (LXRX)?

Yes; investigators reported this is the first trial to demonstrate important clinical benefits for HFpEF patients without diabetes.