Sotagliflozin Provides Consistent Relative Risk Reduction in Heart Failure and Major Cardiovascular Events Across All Age Ranges, Including Greater Than 75, in Data Presented at the European Society of Cardiology (ESC) 2025 Congress

Rhea-AI Summary

Lexicon Pharmaceuticals (NASDAQ:LXRX) presented compelling post-hoc analysis results for sotagliflozin at the ESC 2025 Congress in Madrid. The analysis, pooling data from SCORED and SOLOIST-WHF trials with nearly 12,000 participants, demonstrated consistent cardiovascular benefits across all age groups.

The study showed sotagliflozin, a dual SGLT-1 and SGLT-2 inhibitor, reduced heart failure endpoints and major cardiovascular events regardless of age. Key findings include reduction in cardiovascular death and heart failure hospitalization (8.5 vs 11.8 events/100 person-years) and decreased MACE events (5.7 vs 7.1 events/100 person-years). The drug showed particular efficacy in patients over 65, who represented 70% of the study population.

Positive

• Consistent reduction in cardiovascular events across all age groups, including elderly patients over 75
• Strong efficacy data in large study population of 12,000 participants
• Demonstrated benefits in high-risk elderly population, which represents a significant market opportunity
• FDA-approved drug shows potential for expanded use in heart failure patients

Negative

• None.

Insights

Pharmaceutical Clinical Trials Expert

Lexicon's sotagliflozin shows consistent cardiovascular benefits across all age groups, including elderly patients often excluded from trials.

Lexicon Pharmaceuticals has presented compelling post-hoc analysis from the SCORED and SOLOIST-WHF trials demonstrating that sotagliflozin, their dual SGLT-1/SGLT-2 inhibitor, provides consistent cardiovascular benefits regardless of patient age. This analysis is particularly noteworthy as it included a robust dataset of nearly 12,000 participants with approximately 70% aged 65 or older, addressing a critical demographic often underrepresented in clinical trials despite having high rates of type 2 diabetes, chronic kidney disease, and heart failure.

The data revealed that sotagliflozin reduced the primary endpoint of total cardiovascular death and heart failure events with a hazard ratio of 0.72 overall, showing similar efficacy in patients under 65 (HR: 0.68) and those 65 and older (HR: 0.73). For major adverse cardiovascular events (MACE), sotagliflozin demonstrated a hazard ratio of 0.80 across age groups. These consistent relative risk reductions regardless of age are clinically meaningful, as elderly patients typically face substantially higher absolute risks for these outcomes.

The inclusion of patients over 75 years old is especially significant, as this population is frequently excluded from cardiovascular outcome trials despite having the highest event rates. This analysis helps fill an important evidence gap in geriatric cardiology and supports the drug's utility in a broader population than many competing therapies. What distinguishes sotagliflozin from other SGLT inhibitors is its dual mechanism targeting both SGLT-1 and SGLT-2, which may contribute to its consistent efficacy profile across these age demographics.

Oral presentation highlighted improvements in heart failure endpoints and major adverse cardiovascular events (MACE) among older adults irrespective of age

THE WOODLANDS, Texas, Sept. 02, 2025 (GLOBE NEWSWIRE) -- Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX) announced that a post-hoc analysis (“Efficacy of Sotagliflozin Among Older Adults: A Pooled Analysis of SCORED and SOLOIST-WHF”) of clinical data was presented Sunday, August 31, during an oral presentation at the European Society of Cardiology (ESC) 2025 Congress in Madrid, Spain.

It is well-established that the incidence of stroke and myocardial infarction (MI, or heart attack), known collectively as major cardiovascular adverse events (MACE), rises with age, as does incidence of heart failure (HF) events. Sotagliflozin, a dual sodium-glucose cotransport 1 and 2 (SGLT-1 and SGLT-2) inhibitor, was approved by the FDA based on its demonstrated efficacy in improving HF endpoints in patients with chronic kidney disease (CKD) or HF. This latest Lexicon-funded analysis examined how the efficacy of sotagliflozin varies with age, particularly among older adults, and used data pooled from the two previous pivotal Phase 3 studies of sotagliflozin, SCORED and SOLOIST-WHF. The robust data set included nearly 12,000 participants, about 70% of whom were 65 or older. This age group represents a very large population in which type 2 diabetes, CKD and/or worsening HF are relatively common. Patients were evaluated by age, both categorically (≥65 years vs <65 years) and continuously. The primary endpoint was total cardiovascular (CV) death, hospitalization for HF, or urgent visit for HF. Additional endpoints included total MACE. Sotagliflozin demonstrated a consistent reduction in both endpoints, as compared to placebo across the spectrum of age.

“Among patients with type 2 diabetes and either chronic kidney disease or heart failure, the addition of sotagliflozin reduced heart failure endpoints and major adverse cardiovascular events, irrespective of age,” said Rahul Aggarwal, MD, Brigham and Women’s Hospital Heart and Vascular Center, Harvard Medical School, Boston, MA, lead study author and presenter of the oral presentation at ESC 2025. "Our team noted meaningful benefit in older adults, including those over the age of 65 and 75 years, who are often at the highest risk for cardiovascular events.”

“The findings are unique to sotagliflozin among SGLT inhibitors and demonstrate that people of all ages, including elderly patients, can benefit when sotagliflozin is included in their treatment regimen,” said Dr. Craig Granowitz, Lexicon’s senior vice president and chief medical officer. “Future research could focus on benefits from sotagliflozin treatment in heart failure patients with preserved ejection fraction, or HFpEF, a population that is generally older and includes more women than other conditions.”

Study Results

The pooled analysis of SCORED and SOLOIST-WHF included a total of 5,900 (50.0%) and 5,906 (50.0%) patients were in the sotagliflozin and placebo groups, respectively. The median age of such patients was 69 years (interquartile range: 63, 74 years), with 3,588 (30.4%) and 8,218 (69.6%) patients <65 vs ≥65 years old, respectively.

Compared to placebo, sotagliflozin reduced the rate of the primary endpoint (total CV death and hospitalization or urgent visit for HF) overall (8.5 vs 11.8 events/100 person-years [p-y]; hazard ratio [HR]: 0.72), among adults <65 years (7.6 vs 10.2 events/100 p-y; HR: 0.68), and ≥65 years (8.9 vs 12.4 events/100 p-y; HR: 0.73).

Sotagliflozin similarly reduced total MACE compared with placebo (5.7 vs 7.1 events/100 p-y; HR: 0.80), with consistent findings among adults <65 years (5.1 vs 6.2 events/100 p-y; HR: 0.79) and ≥65 years (5.9 events/100 p-y vs 7.4 events/100 p-y; HR: 0.80).

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, hypertrophic cardiomyopathy (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 its other drug candidates, including sotagliflozin. 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 were the key findings of LXRX's sotagliflozin study presented at ESC 2025?

The study showed sotagliflozin reduced cardiovascular death and heart failure hospitalization (8.5 vs 11.8 events/100 person-years) and decreased MACE events (5.7 vs 7.1 events/100 person-years) across all age groups.

How effective was sotagliflozin in elderly patients with heart failure?

Sotagliflozin showed consistent benefits in patients ≥65 years, reducing heart failure events (8.9 vs 12.4 events/100 person-years) and MACE (5.9 vs 7.4 events/100 person-years) compared to placebo.

What percentage of participants in the LXRX sotagliflozin trials were over 65?

Approximately 70% of the nearly 12,000 study participants were 65 or older, representing a significant elderly population with type 2 diabetes, CKD, and/or worsening heart failure.

What is unique about sotagliflozin compared to other SGLT inhibitors?

Sotagliflozin is a dual SGLT-1 and SGLT-2 inhibitor that demonstrated consistent benefits across all age groups, including elderly patients over 75, which is unique among SGLT inhibitors.

What are the potential future applications for LXRX's sotagliflozin?

Future research may focus on benefits in heart failure patients with preserved ejection fraction (HFpEF), a population that is generally older and includes more women than other conditions.