Sotagliflozin Faces Setback as FDA Advisory Committee Recommends Against Approval for T1D and Chronic Kidney Disease
Key Insights
An FDA advisory committee has recommended against approving sotagliflozin for blood glucose control in individuals with type 1 diabetes (search) (T1D) and chronic kidney disease (search) (CKD).
Breakthrough T1D (search) expresses disappointment, emphasizing the unmet need for additional therapies to improve health outcomes and quality of life for those with T1D and CKD.
Lexicon Pharmaceuticals announced they received a “deficiencies preclude discussion” letter from the FDA and will stop pursuing sotagliflozin for use in glucose control in people with T1D and CKD.
Lexicon Pharmaceuticals' sotagliflozin has encountered a setback as a U.S. Food and Drug Administration (FDA) advisory committee recommended against its approval for blood glucose control in individuals with type 1 diabetes (search) (T1D) and chronic kidney disease (search) (CKD). The decision was met with disappointment from Breakthrough T1D (search), formerly JDRF, which has been a strong advocate for the therapy's potential benefits.
Unmet Needs in T1D and CKD
For over a century, insulin has remained the primary treatment for T1D. While advancements in insulin therapies and technologies like continuous glucose monitors and automated insulin delivery systems have improved the lives of many, a significant portion of individuals with T1D still struggle to achieve optimal glycemic control. Recent data indicates that only 26% of individuals with T1D in the United States reach the recommended HbA1c target of less than 7%, highlighting the persistent need for additional therapeutic options. Moreover, people with T1D die 11 years earlier than their non-diabetic counterparts.
Breakthrough T1D (search) emphasizes the urgent need for novel therapies that can improve glycemic control, clinical outcomes, and overall quality of life for individuals with T1D, particularly those with co-existing CKD. The organization believes that sotagliflozin holds promise as an adjunctive therapy to insulin, potentially offering benefits in A1c levels, reduced hypoglycemia, and increased time-in-range.
Sotagliflozin: An SGLT Inhibitor
Sotagliflozin is an SGLT (search) (sodium-glucose co-transporter) inhibitor, a class of oral medications initially developed for type 2 diabetes (T2D). These drugs lower blood sugar by preventing the kidneys from reabsorbing glucose, leading to its excretion through urine. Beyond glucose control, SGLT inhibitors have demonstrated transformative benefits in heart and kidney health in individuals with T2D and even in those without diabetes, along with promoting weight loss and blood pressure reduction.
Potential Benefits for T1D and CKD
Maintaining tight glucose control is crucial for preventing CKD in individuals with T1D. Recent data suggest a significant correlation between high HbA1c levels and accelerated loss of kidney function in those with T1D who already have CKD. Sotagliflozin has shown promise in improving CKD outcomes in trials involving individuals with T2D, leading to the expectation that similar benefits could extend to those with T1D and CKD. While long-term kidney outcome data for sotagliflozin in T1D are still pending, existing data indicate improvements in key biomarkers of kidney function.
Risk of Diabetic Ketoacidosis (DKA)
A key consideration for the safe use of sotagliflozin is the potential risk of diabetic ketoacidosis (search) (DKA). SGLT (search) inhibitors can increase DKA risk in people with T1D, necessitating careful monitoring and management. Experts have convened to address these concerns, resulting in an international consensus on strategies to mitigate DKA risks in individuals with T1D using SGLT inhibitors. It's important to note that DKA is a risk for all individuals with T1D, regardless of SGLT inhibitor use, underscoring the need for vigilance in managing the condition.
Breakthrough T1D's Ongoing Commitment
Despite the FDA advisory committee's recommendation, Breakthrough T1D (search) remains committed to investing in research to develop therapies for kidney disease in T1D. The organization's Improving Lives program supports the development of SGLT (search) inhibitors for T1D, including trials to assess the benefits and risks of this drug class, as well as device-based and other strategies for DKA risk mitigation. Lexicon announced they received a “deficiencies preclude discussion” letter from the FDA and will stop pursuing sotagliflozin for use in glucose control in people with T1D and CKD.