The European Commission has granted marketing authorization for Zynquista ( Sotagliflozin ), at once-daily doses of 200 mg and 400 mg, for use as an adjunct to Insulin therapy to improve glycemic control in adults with type 1 diabetes ( T1D ) mellitus and a body mass index greater than or equal to 27 kg/m2, who could not achieve adequate glycemic control despite optimal Insulin therapy.
Sotagliflozin is an oral dual inhibitor of two proteins responsible for glucose regulation known as sodium-dependent glucose co-transporter types 1 and 2 ( SGLT1 and SGLT2 ).
SGLT1 is responsible for glucose absorption in the gastrointestinal tract, and SGLT2 is responsible for glucose reabsorption by the kidney.
The marketing authorization is based on evidence including data from the in tandem clinical trial program, which included three phase 3 clinical trials assessing the safety and efficacy of Sotagliflozin, involving approximately 3,000 adults with inadequately controlled type 1 diabetes.
These three trials have demonstrated that treatment with Sotagliflozin, when given to adults with inadequately controlled T1D as an oral adjunct to Insulin, resulted in consistent and significant reductions from baseline at 24 weeks in average blood sugar ( HbA1c ), body weight, systolic blood pressure, a significant improvement of time in target blood sugar range and improved patient-reported outcomes, versus insulin alone, at both 200-mg and 400-mg doses.
This was achieved without the usual increase in severe hypoglycemia that comes with intensification of Insulin and with less events of severe hypoglycemia in the 400-mg dose at 52 weeks.
Consistent with selective SGLT2 inhibitors, clinical trials with Sotagliflozin have shown an increased risk of genital mycotic infections and diabetic ketoacidosis ( DKA ), which is acknowledged to affect people with T1D more frequently than those with type 2 diabetes ( T2D ).
The risk of diabetic ketoacidosis will be addressed by careful selection of patients for treatment with Sotagliflozin and through a risk management plan and a mitigation strategy, including patient, healthcare professional and care giver educational activities, that will support its safe use.
Zynquista is also currently being evaluated in a program of 11 clinical trials in adults with T2D, including two trials in people living with T2D and renal impairment, and two large cardiovascular outcomes trials. ( Xagena )
Source: Sanofi, 2019