Sotagliflozin Not Approved as Type 1 Diabetes Add-On

The US Food and Drug Administration (FDA) declined to approve sotagliflozin (Zynquista) as an adjunct to insulin therapy for people with type 1 diabetes (T1D) and chronic kidney disease (CKD).

Announced by Lexicon Pharmaceuticals, Inc., on December 20, 2024, the FDA’s complete response letter decision follows the October 31, 2024 11-3 vote of the FDA’s Endocrinologic and Metabolic Drugs advisory panel against the benefits of the drug outweighing the risks among people with T1D and CKD.

In March 2019, the FDA declined to approve sotagliflozin, a dual inhibitor of sodium-glucose cotransporter (SGLT) types 1 and 2, as adjunctive treatment to insulin therapy to improve glycemic control in adults with T1D. At that time, the FDA determined that the risk for diabetic ketoacidosis outweighed the benefits among those patients.

In its resubmission, Lexicon narrowed the approval they were seeking to people with T1D who also have CKD with estimated glomerular filtration rate (eGFR) of 45 to 2, 60 to 2, and ≥ 90 mL/min/1.73 m².

This time, the company said that patient group would accrue greater benefit from the same A1c reduction, given the known kidney benefits of the SGLT2 drug class. At the October advisory panel meeting, some members felt the drug benefits did outweigh its risks for the subgroup with eGFR of ≥ 60, but lacking specific subgroup data, they couldn’t support the risks outweighing the benefits overall.

In 2022, FDA approved sotagliflozin under the name Inpefa to reduce the risk for cardiovascular death, hospitalization for heart failure, and urgent heart failure visit in adults with heart failure or adults with type 2 diabetes, CKD, and other cardiovascular risk factors.

Anticipating the complete response letter, in November 2024 Lexicon announced it would completely eliminate all promotional efforts for Inpefa and planned commercial activities for Zynquista, but it will continue to manufacture Inpefa and make it available for patients and existing prescribers.

Lexicon said it will “reemerge” as a “clinical development-focused company,” concentrating on its current pipeline that includes the Phase 2b PROGRESS study evaluating LX9211 in diabetic peripheral neuropathic pain, with topline data anticipated in early 2025; the pivotal Phase 3 SONATA HCM study evaluating sotagliflozin in hypertrophic cardiomyopathy, with enrollment underway; and studies of LX9851, a novel, non-incretin oral development candidate in obesity and associated cardiometabolic disorders.

Miriam E. Tucker is a freelance journalist based in the Washington, DC, area. She is a regular contributor to Medscape Medical News, with other work appearing in the Washington Post, NPR’s Shots blog, and Diatribe. She is on X @MiriamETucker.