Published Data in The Lancet Diabetes & Endocrinology Highlights Unique Efficacy Benefits of Sotagliflozin to Reduce Major Adverse Cardiovascular Events (MACE)

Rhea-AI Summary

Lexicon Pharmaceuticals (Nasdaq: LXRX) announced that The Lancet Diabetes & Endocrinology published a study highlighting the unique efficacy of sotagliflozin in reducing major adverse cardiovascular events (MACE). The study, a secondary analysis of the SCORED randomized trial, demonstrated that sotagliflozin, a dual SGLT1 and SGLT2 inhibitor, significantly reduced the risk of heart attack (MI) and stroke in patients with type 2 diabetes (T2D), chronic kidney disease (CKD), and high cardiovascular (CV) risk.

Patients on sotagliflozin had a lower rate of MACE outcomes (4.8 events per 100 person-years [p-y]) compared to placebo (6.3 events per 100 p-y) with a hazard ratio (HR) of 0.77, 95% confidence interval (CI) of 0.65-0.91, and P=0.002. The drug also reduced the rate of MI (1.8 events per 100 p-y vs. 2.7 events per 100 p-y, HR: 0.68, 95% CI: 0.52-0.89, P=0.004) and stroke (1.2 events per 100 p-y vs. 1.8 events per 100 p-y, HR: 0.66, 95% CI: 0.48-0.91, P=0.012).

Dr. Deepak L. Bhatt, Director at Mount Sinai Fuster Heart Hospital, emphasized that sotagliflozin is the only SGLT inhibitor to show significant reductions in both heart attack and stroke.

Positive

• Sotagliflozin significantly reduces major adverse cardiovascular events (MACE) in high-risk patients.
• The drug shows unique efficacy in lowering heart attack and stroke rates compared to other SGLT inhibitors.
• Sotagliflozin reduced MACE rates to 4.8 events per 100 person-years from 6.3 events per 100 person-years with placebo.
• Heart attack rates decreased to 1.8 events per 100 person-years from 2.7 events per 100 person-years with placebo.
• Stroke rates reduced to 1.2 events per 100 person-years from 1.8 events per 100 person-years with placebo.

Negative

• None.

Insights

Medical Research Analyst

The publication of sotagliflozin's SCORED trial analysis in The Lancet Diabetes & Endocrinology represents a pivotal development for Lexicon Pharmaceuticals, demonstrating unprecedented efficacy in reducing cardiovascular events. The data reveals several critical advantages:

Key statistical outcomes:

• MACE reduction: 23% (HR: 0.77, p=0.002)
• Myocardial infarction reduction: 32% (HR: 0.68, p=0.004)
• Stroke reduction: 34% (HR: 0.66, p=0.012)

The dual SGLT1 and SGLT2 inhibition mechanism of sotagliflozin creates a distinct competitive advantage in the $25 billion SGLT inhibitor market. This differentiation is particularly significant as it addresses a critical gap in current treatment options for high-risk cardiovascular patients with type 2 diabetes and chronic kidney disease.

The market implications are substantial. Cardiovascular complications represent the largest cost burden in diabetes care, with annual expenses exceeding $37,000 per patient with cardiovascular disease. Sotagliflozin's demonstrated ability to reduce both heart attacks and strokes - a unique feature not shown by other SGLT inhibitors - positions it favorably for premium pricing and preferred formulary placement.

The validation from a prestigious peer-reviewed journal strengthens Lexicon's position in discussions with payers and healthcare providers. This could accelerate market adoption, particularly among cardiologists and endocrinologists who treat high-risk patients where the drug's dual mechanism provides clear advantages over existing options.

Data reinforce unique clinical advantages of sotagliflozin

Published study is aligned with research presented in December 2024 at the American Society of Hematology showing clinical benefits of sotagliflozin compared to empagliflozin

THE WOODLANDS, Texas, Feb. 18, 2025 (GLOBE NEWSWIRE) -- Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX) today announced The Lancet Diabetes & Endocrinology has published a research paper analyzing the ability of sotagliflozin, a dual SGLT1 and SGLT2 inhibitor, to reduce the risks of life-threatening cardiovascular outcomes. 

The findings from the study, “Reduction in Major Adverse Cardiovascular Events with Sotagliflozin: A Prespecified Analysis of the SCORED Randomized Trial,” concluded that the ischemic benefit of sotagliflozin on both heart attack (myocardial infarction, or MI), and stroke reduction has not been shown by other SGLT inhibitors. The researchers note that sotagliflozin reduced major adverse cardiovascular events (MACE), MI, and stroke among patients with type 2 diabetes (T2D), chronic kidney disease (CKD), and high cardiovascular (CV) risk.

The study was a secondary analysis of SCORED, a double-blind, placebo-controlled, randomized clinical trial enrolling patients with T2D and CKD. A pre-specified outcome was total MACE, which was defined as a composite of total CV death, nonfatal MI, and nonfatal stroke. Other outcomes included total MI and total stroke.

Patients in the sotagliflozin group had a lower rate of MACE outcomes (4.8 events per 100 person-years [p-y]) compared with the placebo group (6.3 events per 100 p-y) (hazard ratio [HR]: 0.77; 95% confidence interval [CI]: 0.65-0.91; P=0.002). MACE benefit was consistent across pre-specified subgroups. Additionally, sotagliflozin reduced the rate of MI (1.8 events per 100 p-y) compared with the placebo group (2.7 events per 100 p-y) (HR: 0.68; 95% CI: 0.52-0.89; P=0.004) and of stroke (1.2 events per 100 p-y vs 1.8 events per 100 p-y) (HR: 0.66, 95% CI: 0.48-0.91, P=0.012).

“Our research team found that sotagliflozin is the only SGLT inhibitor to demonstrate significant reduction of both heart attack and stroke,” said Deepak L. Bhatt, MD, MPH, MBA, FACC, FAHA, FESC, MSCAI, Director, of the Mount Sinai Fuster Heart Hospital, and the Dr. Valentin Fuster Professor of Cardiovascular Medicine at the Icahn School of Medicine at Mount Sinai, New York, NY. The Icahn School of Medicine receives research funding for Dr. Bhatt’s role as the Chair of SCORED.

“When you look at the published and presented findings holistically, you get a clear picture of how and why sotagliflozin stands apart from all other SGLT inhibitors,” said Craig Granowitz, M.D., Ph.D., Lexicon’s senior vice president and chief medical officer.

Click here to access the study abstract published by The Lancet Diabetes & Endocrinology on February 14, 2025.

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.

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 sotagliflozin and Lexicon’s financial position and long-term outlook on its business, 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 conduct preclinical and clinical development and obtain necessary regulatory approvals of its 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, 2023, 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

Media Contact
Sheryl Seapy
Real Chemistry
corpcomm@lexpharma.com

FAQ

What are the key findings of the sotagliflozin study published in The Lancet Diabetes & Endocrinology?

The study found that sotagliflozin significantly reduces major adverse cardiovascular events (MACE), heart attack, and stroke in patients with type 2 diabetes, chronic kidney disease, and high cardiovascular risk.

How effective is sotagliflozin in reducing MACE events compared to placebo?

Sotagliflozin reduced MACE events to 4.8 per 100 person-years compared to 6.3 per 100 person-years for placebo, with a hazard ratio of 0.77.

What impact does sotagliflozin have on heart attack rates?

Sotagliflozin reduced heart attack rates to 1.8 events per 100 person-years compared to 2.7 events per 100 person-years for placebo.

How does sotagliflozin affect stroke rates?

Sotagliflozin reduced stroke rates to 1.2 events per 100 person-years compared to 1.8 events per 100 person-years for placebo.

What makes sotagliflozin unique among SGLT inhibitors?

Sotagliflozin is the only SGLT inhibitor shown to significantly reduce both heart attack and stroke rates.

What was the scope of the SCORED trial analyzed in the study?

The SCORED trial was a double-blind, placebo-controlled, randomized clinical trial enrolling patients with type 2 diabetes and chronic kidney disease.

What were the pre-specified outcomes of the SCORED trial?

The pre-specified outcomes included total MACE, defined as a composite of total cardiovascular death, nonfatal heart attack, and nonfatal stroke, along with total heart attack and total stroke.