Sotagliflozin Meets End Point in Second Type 1 Diabetes Trial

Miriam E Tucker

December 23, 2016

A second randomized clinical trial suggests that the novel investigational agent sotagliflozin could be an effective adjunct to insulin therapy in patients with type 1 diabetes.

Sotagliflozin is a first-in-class oral dual inhibitor of sodium-glucose cotransporter types 1 and 2 (SGLT1 and SGLT2) and thereby acts on both glucose absorption in the gastrointestinal tract and glucose reabsorption in the kidney. Its effects are independent of insulin.

The drug was developed by Lexicon, which licensed it to Sanofi in November 2015. If approved, sotagliflozin would be the first oral agent licensed for people with type 1 diabetes as an adjunct to insulin for improving glycemic control.

Lexicon reported results from InTandem1, the first of three pivotal double-blind, placebo-controlled phase 3 trials, in September. InTandem1 was conducted in North America; a second trial, InTandem2, has the same design but took place in Europe and Israel.

Top-line results for InTandem2 were announced December 22 during a Lexicon conference call.

Study participants were 782 adults with type 1 diabetes on insulin pump or multiple daily injections with a baseline HbA1c of 7.0% to 11.0%. Prior to randomization, they underwent a 6-week insulin dose-optimization period, with the aim of improving glycemic control with insulin alone.

After optimization, participants were randomized to one of three arms: once-daily 200-mg or 400-mg sotagliflozin or placebo. At randomization, average HbA1c was 7.8% in the placebo group and 7.7% in the two sotagliflozin dose groups.

As with InTandem1, the study met its primary end point, with mean HbA1c reductions from baseline after 24 weeks of treatment of 0.39% with 200-mg sotagliflozin and 0.37% with 400-mg sotagliflozin (both P < .001) vs 0.03% with placebo.

For placebo, 200-mg sotagliflozin, and 400-mg sotagliflozin, the incidence of treatment-emergent adverse events was 51.4%, 55.9%, and 54.4%, respectively, and the incidence of serious adverse events was 3.5%, 4.2%, and 4.2%, respectively. Discontinuation rates because of adverse events were 1.6%, 1.9%, and 3.0%, respectively. Two deaths occurred in the placebo arm during the study.

Severe hypoglycemia occurred in 2.7%, 3.8%, and 2.3% of patients in the placebo, 200-mg, and 400-mg sotagliflozin arms, respectively. There were no diabetic ketoacidosis events in the placebo group, whereas one event (0.4%) occurred in the 200-mg sotagliflozin group and three events (1.1%) occurred in the 400-mg sotagliflozin group.

The third phase 3 clinical trial, inTandem3, enrolled approximately 1400 patients with type 1 diabetes treated with 400-mg sotagliflozin and insulin therapy, but without the optimization period. Data collection for that trial is expected to end in March 2017. Sanofi is also conducting phase 3 clinical trials of sotagliflozin in patients with type 2 diabetes.

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