Post hoc analysis of clinical research data shows that sotagliflosin added to insulin therapy in type 1 diabetes reduced the risk of hypoglycemia, a potentially life-threatening hypoglycemia. The data was recently presented at the 85th scientific session of the American Diabetes Association Conference. Furthermore, this effect appears to be consistent across EGFR subgroups, suggesting that sotagliflosin maintains this similar trend regardless of renal function.
Type 1 diabetes is an autoimmune disease affecting approximately 2 million Americans, about 5% to 10% of all diabetic cases, according to the Centers for Disease Control and Prevention (CDC).
The aim of this post hoc analysis was to assess the effect of renal function on the risk of hypoglycemia in patients with type 1 diabetes who were being treated with the dictionary drug sotagliflozin as an adjunct to optimized insulin therapy.
Sotagliflozin is an inhibitor of SGLT2 and SGLT1, responsible for glucose regulation in the kidney and gastrointestinal tract, respectively.
This analysis shows that adding sotagliflozin to insulin improves A1C. M. Belinda Hardin, Pharm.D. Lexicon's senior director of Medical Communications said in an interview. “While patients with type 1 diabetes still need control of A1c, even the best treatments they have available. We know that about 50% to 60% of patients are not reaching A1C's ADA target.”
The American Diabetes Association (ADA) recommends targets of less than 7% of A1C for most adults.
Hardin also said that adding sotagliflozin to insulin would result in improved measurements, a measure that assesses how long a patient is within the target blood glucose range. The ADA's recommendation is that at least 70% of people's days are on time.
At baseline, most patients only spent 10 to 12 hours in the distance, Hardin said. Sotagliflozin is added within the range from 2 to 4 hours.
The researchers analyzed pooled data for Intandem 1 and Intandem 2, which identically designed a 52-week Phase 3 clinical trial comparing 200 and 400 mg of sotagliflozin per day with placebo when added to optimized insulin therapy. In these studies, recorded hypoglycemia was defined as blood glucose levels below 70 mg/dL and ≤55 mg/dL, according to the definition of ADA level 3, and as a severe hypoglycemia.
In terms of adverse events, adding sotagliflozin to insulin increases the risk that patients develop diabetic ketosidosis. This is a serious complication that the body cannot use sugar for energy. The liver begins to break down fats for fuel, producing acids called ketones.
“Diabetic ketoacidosis was increased in both treatment groups,” Hardin said. “The good news is that there wasn't increased on the baseline we knew.”
Related: FDA Problems Zynquista Complete Reaction in Type 1 Diabetes
The increased risk of diabetic ketoacidosis with treatment with sotagliflozin led to the FDA's publication of a full response letter in December 2024 as an adjunct to insulin therapy for glycemic control in adults with type 1 diabetes and chronic kidney disease (CKD). The October 2024 Regulatory Advisory Committee voted between 11 and 3 against Sotagliflozin's approval, saying its benefits did not outweigh the risks. If it had been approved, therapy would have had the Zynquista brand name.
Hardin said Lexicon is being discussed continuously with the FDA about the NDA. “Our goal is to continue collecting scientific data from previous exams, not just ongoing research,” she said. “There is a study that continues to sotagliflosin in this patient population, and we are keeping the door open with the FDA to collect additional data we want to see. The route is still open.”
Sotagliflozin was approved as INPEFA by the FDA in May 2023 and as a one-day oral tablet that reduces the risk of heart failure or cardiac failure in adults with type 2 diabetes, chronic kidney disease, and other cardiovascular risk factors.