Lexicon Submits Additional Benefit-Risk Data to FDA for Sotagliflozin for Type 1 Diabetes

Lexicon Pharmaceuticals, Inc. has submitted additional clinical data to the US Food and Drug Administration (FDA) for the New Drug Application for sotagliflozin (Zynquista), a potential adjunct to insulin for glycemic control in adults with type 1 diabetes (T1D).1

This additional data follows a complete response letter from the FDA in December 2024, which cited concerns of increased risk of diabetic ketoacidosis as a result of sotagliflozin treatment. After further discussions with the FDA, Lexicon was granted a Type D meeting and has submitted data from 3 ongoing studies supporting the risk-benefit profile of sotagliflozin in T1D.1

“There has been an outpouring of patient support advocating for the approval of Zynquista in T1D,” said Mike Exton, PhD, chief executive officer and director of Lexicon Pharmaceuticals. “While we are no longer investing in clinical programs for Zynquista, we remain committed to exploring all opportunities to bring this medicine to patients, whose support for approval is unwavering.”1

The first of these studies, Steno1, is a randomized, open-label, multi-center study conducted by the Steno Diabetes Center. The trial aims to investigate multifactorial intervention (MFI) in patients with T1D at high risk of cardiovascular disease (CVD) with ambitious treatment targets. Patients were randomly assigned to semaglutide, sotagliflozin, finerenone, ezetimibe, and/or PCSK9 inhibitors. The primary endpoint is to determine whether MFI is superior to standard care regarding a composite of major adverse cardiovascular events (MACE) and hospitalization for heart failure (HHF).2

The second study, conducted by the Joslin Diabetes Center, is titled SUGARNSALT. Investigators aim to utilize a diabetic ketoacidosis prevention program over 3 years to test the kidney benefit of sotagliflozin in 150 patients with T1D and moderate to advanced diabetic kidney disease. The program includes participant education, close follow-up with study staff, systematic ketone body self-monitoring via a study-provided meter, and continuous glucose monitoring.3

The final study, titled SOPHIST, is being conducted by the University of Dundee. Investigators aim to compare the quality of life of patients taking sotagliflozin versus those taking placebo. The trial will run for roughly 6 months, during which time patients will take either sotagliflozin or placebo once daily for 4 months. Investigators plan to run the trial for 26 months.4

Sotagliflozin is an oral SGLT1 and SGLT2 inhibitor, which has been studied for heart failure (HF), diabetes, and chronic kidney disease in various clinical studies involving upwards of 20,000 patients. It was approved in May 2023 for the treatment of HF, including HF with reduced ejection fraction, HF with preserved ejection fraction, HF in patients with type 2 diabetes mellitus, and HF in patients with chronic kidney disease.5

Lexicon Pharmaceuticals expects to receive FDA feedback from the Type D meeting by the end of September 2025.1

References

1. Lexicon Pharmaceuticals, Inc. Lexicon Pharmaceuticals Announces Submission of Additional Data to US FDA Supporting the Benefit-Risk Profile of Zynquista in Type 1 Diabetes. GlobeNewswire. September 8, 2025. Accessed September 8, 2025. https://www.globenewswire.com/news-release/2025/09/08/3146089/0/en/Lexicon-Pharmaceuticals-Announces-Submission-of-Additional-Data-to-U-S-FDA-Supporting-the-Benefit-Risk-Profile-of-Zynquista-in-Type-1-Diabetes.html

2. Steno Diabetes Center Copenhagen. Multifactorial Intervention to Reduce Cardiovascular Disease in Type 1 Diabetes (Steno1). ClinicalTrials.gov identifier: NCT06082063. Updated January 10, 2025. Accessed September 8, 2025. https://www.clinicaltrials.gov/study/NCT06082063

3. Doria A. Sotagliflozin to Slow Kidney Function Decline in Persons With Type 1 Diabetes and Diabetic Kidney Disease (SUGARNSALT). ClinicalTrials.gov identifier: NCT06217302. Updated August 26, 2025. Accessed September 8, 2025. https://www.clinicaltrials.gov/study/NCT06217302

4. SOPHIST Clinical Trial. University of Dundee. Accessed September 8, 2025. https://sites.dundee.ac.uk/sophist-trial/

5. American College of Cardiology. FDA Update: Sotagliflozin Approved for Broad HF Treatment. ACC. June 5, 2023. Accessed September 8, 2025. https://www.acc.org/Latest-in-Cardiology/Articles/2023/06/05/18/34/FDA-Update-Sotagliflozin-Approved-For-Broad