Lexicon Reports Positive Results for Sotagliflozin in Type 1 Diabetes

Lexicon Pharmaceuticals has reported that its pivotal phase 3 trial of sotagliflozin, a first-in-class treatment for type 1 diabetes (T1D), has met its primary endpoint with statistically significant reductions in glycated hemoglobin (A1C) for these patients at 24 weeks.

Top-line results from the trial, inTandem2, show that patients had mean A1C reductions of 0.39% from baseline while taking 200 mg of the sotagliflozin, and mean A1C reductions of 0.37% on 400 mg of the drug, compared with a mean reduction of 0.03% on placebo. According to a statement from Lexicon, the results were achieved “with a favorable overall safety profile, including rates of severe hypoglycemia similar to placebo and low overall rates of diabetic ketoacidosis.”

Sotagliflozin is an oral dual inhibitor, which means it targets 2 proteins that affect glucose regulation in patients with diabetes. That means the drug targets not only the sodium glucose co-transporter-2 (SGLT2) protein, which is involved in glucose reabsorption in the kidney, but also the SGLT1 protein, which affects glucose absorption in the gastrointestinal tract.

There are several drugs already approved which are SGLT2 inhibitors, which allow excess sugar to be expelled through the urinary tract. SGLT2 inhibitors are approved to treat patients with type 2 diabetes and are being studied in patients with T1D, who have taken it alongside insulin. Patients in the inTandem2 study were all on optimized insulin therapy.

Lexicon has a collaborative agreement with Sanofi to license and develop sotagliflozin. There is an additional study, inTandem3, involving 1400 patients treated with sotagliflozin (400 mg/daily) or placebo on a background of insulin therapy, but without insulin optimization prior to randomization. Sanofi is responsible for this trial, according to the statement.

“The inTandem2 study demonstrated a compelling safety and efficacy profile for sotagliflozin in adults living with type 1 diabetes,” said Thomas Danne, MD, head of the Center for Children Endocrinology and Diabetes, at the Children’s Hospital on the Bult, in Germany. “The potential to significantly lower A1C levels without an increase in hypoglycemia would represent a major shift in the treatment paradigm for type 1 diabetes.”