Data Demonstrating Sotagliflozin Reduces the Risk of Clinically Important Hypoglycemic Events in Adults with Type 1 Diabetes When Added to Insulin Presented at the 85th Scientific Sessions of the American Diabetes Association (ADA)

Rhea-AI Summary

Lexicon Pharmaceuticals (LXRX) presented post-hoc analysis data at the ADA's 85th Scientific Sessions showing that sotagliflozin, when added to insulin therapy, reduces hypoglycemic events in Type 1 diabetes patients. The analysis, based on inTandem 1 and 2 Phase 3 trials data, demonstrated that sotagliflozin treatment resulted in lower hypoglycemia rates compared to placebo, particularly in patients with blood glucose ≤55 mg/dL. The effect was consistent across different kidney function groups. This finding is significant as hypoglycemia accounts for 5% of T1D hospitalizations and up to 10% of T1D deaths, with chronic kidney disease affecting 20-40% of T1D patients being a major risk factor.

Positive

• Sotagliflozin demonstrated reduction in hypoglycemic events when added to insulin therapy
• Treatment showed consistent benefits across different kidney function groups
• Lower severe hypoglycemia event rates compared to placebo
• Results support potential improvement in patient care for Type 1 diabetes management

Negative

• None.

Insights

Endocrinologist

Lexicon's sotagliflozin shows promising hypoglycemia safety profile in T1D patients across kidney function levels, strengthening its clinical value proposition.

This post-hoc analysis of the inTandem 1 and 2 trials reveals significant clinical benefits for sotagliflozin as an adjunct to insulin therapy in type 1 diabetes (T1D). The data demonstrate that sotagliflozin not only improved glycemic control but actually reduced hypoglycemic events compared to placebo, particularly for blood glucose levels ≤55 mg/dL. This is clinically meaningful because hypoglycemia remains a major barrier to optimal diabetes management, accounting for 5% of T1D hospitalizations and up to 10% of T1D deaths.

What makes these findings particularly valuable is the consistent benefit across different kidney function levels, including patients with reduced eGFR. This is critically important since 20-40% of T1D patients develop chronic kidney disease (CKD), which independently increases hypoglycemia risk. Most diabetes medications require dose adjustments or are contraindicated in kidney impairment, so having an option that maintains its safety profile across varying eGFR levels addresses an unmet clinical need.

The dual SGLT1/2 inhibition mechanism of sotagliflozin likely contributes to this beneficial hypoglycemia profile. While SGLT2 inhibition reduces glucose reabsorption in the kidneys, the added SGLT1 inhibition in the intestine provides a complementary glucose-lowering effect that may be less dependent on kidney function, potentially explaining the consistent benefits across eGFR subgroups.

Pharmaceutical Market Analyst

This post-hoc analysis strengthens sotagliflozin's competitive positioning in the diabetes market by addressing a critical safety concern. The reduction in hypoglycemic events across all kidney function levels represents a significant clinical differentiator that could drive physician adoption and payer acceptance. Current T1D management focuses heavily on avoiding hypoglycemia while achieving glycemic targets, making sotagliflozin's dual benefit profile particularly valuable.

The consistency of benefit across different eGFR levels is commercially significant as it potentially broadens the eligible patient population to include those with compromised kidney function – approximately 20-40% of the T1D market. Many competing therapies have restrictions or warnings regarding use in patients with reduced kidney function, giving sotagliflozin a potential market advantage.

The timing of this presentation at the ADA Scientific Sessions maximizes visibility among key prescribers and opinion leaders. The favorable hypoglycemia data could help address physician concerns about adding agents to insulin therapy and potentially accelerate clinical adoption. Additionally, the reduced hospitalization risk implied by lower severe hypoglycemia rates could strengthen the drug's value proposition to payers, potentially supporting favorable formulary positioning.

While Lexicon still faces challenges in the competitive SGLT inhibitor landscape, these differentiated safety data help establish a unique clinical profile for sotagliflozin that addresses a significant unmet need in T1D management.

Oral presentation highlighted the post-hoc analysis during the “Interventions to Prevent Hypoglycemia: Bench to Bedside” session

Treatment with sotagliflozin resulted in no increased risk and a reduction in hypoglycemia events, particularly in patients with blood glucose ≤55 mg/dL

THE WOODLANDS, Texas, June 23, 2025 (GLOBE NEWSWIRE) -- Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX) announced that a post-hoc analysis of clinical study data showing a reduction in hypoglycemic events when sotagliflozin was added to optimized insulin therapy for people with type 1 diabetes (T1D) was presented yesterday during the 85th Scientific Sessions of the American Diabetes Association (ADA) in Chicago, Illinois.

The ADA emphasizes that hypoglycemia remains an important patient management issue in T1D. Its Standards of Care in Diabetes -- 2025 clinical update states, "Health care professionals should be vigilant in preventing hypoglycemia." In addition, severe hypoglycemia accounts for 5% of T1D hospitalizations and up to 10% of T1D deaths.

Chronic kidney disease (CKD) is an important, independent risk factor for hypoglycemia in people with T1D. Approximately 20% to 40% of people with T1D develop CKD. Treatment with sotagliflozin as an adjunct to insulin therapy has been shown to improve glycemic control while also reducing hypoglycemic events.

The aim of this post-hoc analysis was to evaluate the effect of kidney function on hypoglycemia risk in patients with T1D who were being treated with sotagliflozin, a dual inhibitor of SGLT 1 and 2, as an adjunct to optimized insulin therapy. Researchers analyzed pooled data from inTandem 1 and inTandem 2, identically designed 52-week Phase 3 clinical trials in which once-daily 200 mg and 400 mg doses of sotagliflozin were compared to placebo when added to optimized insulin therapy. In these studies, documented hypoglycemia was defined as blood glucose of ≤ 70 mg/dL and ≤ 55 mg/dL, and severe hypoglycemia per the ADA Level 3 definition.

Results were evaluated by subgroups defined by estimated glomerular filtration rate (eGFR) cut points: eGFR < 60 ml/min/1.73m², eGFR ≥ 60 to < 90 ml/min/1.73m², and eGFR ≥ 90 ml/min/1.73m². The overall trend favored sotagliflozin, indicating no increased risk and a reduction in hypoglycemia events, particularly in patients with blood glucose ≤55 mg/dL. Notably, the effect appears consistent across eGFR subgroups, suggesting that sotagliflozin maintains this similar trend regardless of kidney function. Treatment with sotagliflozin generally resulted in severe hypoglycemia event rates lower than that of placebo.

“This analysis is important because it demonstrated that adding sotagliflozin on top of optimized insulin therapy resulted in fewer people developing significant hypoglycemia,” said Craig Granowitz, M.D., Ph.D., Lexicon’s senior vice president and chief medical officer. “Practitioners recognize that hypoglycemia remains an obstacle to optimal care in people with diabetes.”

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 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 are the key findings of LXRX's sotagliflozin study presented at ADA 2025?

The study showed that sotagliflozin, when added to insulin therapy, reduces hypoglycemic events in Type 1 diabetes patients, particularly in those with blood glucose ≤55 mg/dL, with consistent effects across different kidney function groups.

How does sotagliflozin affect hypoglycemia risk in Type 1 diabetes patients?

Sotagliflozin demonstrated no increased risk and actually showed a reduction in hypoglycemia events, with lower severe hypoglycemia rates compared to placebo when added to optimized insulin therapy.

What is the significance of LXRX's sotagliflozin study for kidney disease patients?

The study showed that sotagliflozin's benefits in reducing hypoglycemia were consistent across all kidney function groups, which is important as 20-40% of Type 1 diabetes patients develop chronic kidney disease.

What were the design parameters of LXRX's sotagliflozin clinical trials?

The analysis pooled data from inTandem 1 and 2, which were 52-week Phase 3 trials comparing daily 200mg and 400mg doses of sotagliflozin to placebo when added to optimized insulin therapy.

What is the current impact of hypoglycemia on Type 1 diabetes patients?

Hypoglycemia remains a significant management issue, accounting for 5% of Type 1 diabetes hospitalizations and up to 10% of deaths, making prevention a key focus in diabetes care.