European Commission Approves Zynquista, First Dual SGLT Inhibitor for T1D
New drug Zynquista (sotagliflozin), developed by Lexicon and Sanofi, has been granted marketing authorization by the European Commission for adults with Type 1 diabetes with a body mass index ≥ 27 kg/m2, who could not achieve adequate glycemic control despite optimal insulin therapy. The oral medication is an SGLT-1 and 2 inhibitor taken in addition to insulin. Zynquista is the first dual SGLT-1/2 inhibitor approved for use in Type 1 diabetes, and the second oral medication approved for use in Type 1 diabetes.
Trial results for Zynquista identified a notable reduction in HbA1c levels and increased time in range (between 3.9-10.0 mmol/L70-180 mg/dl). Additionally, the medication has been shown to help reduce insulin requirements, assist with weight loss, and help prevent glucose spikes after meals. However, clinical research also showed that diabetic ketoacidosis (DKA) was noted to be substantially higher in trial patients using the drug. The European approval comes with a note that DKA risk must be addressed with appropriate patient selection, education, and ketone monitoring in place.
Just last month, the FDA declined to approve the same drug, citing safety concerns around possible increased risk of DKA. Preliminary recommendations from the Committee for Medicinal Products for Human Use (CHMP) in Europe had been considerably more positive than the recommendations from the FDA Advisory Committee in the United States. The FDA did not issue an outright rejection, but a “Complete Response Letter” likely asking for further data and risk management. Lexicon and Sanofi have announced that they will “work closely with the FDA to determine the appropriate next steps” for an approval of Zynquista in the United States.
Zynquista is an oral inhibitor of sodium-dependent glucose co-transporters 1 and 2, two proteins responsible for glucose regulation. SGLT-1 works in the gastrointestinal tract and SGLT-2 in the kidneys. SGLT-2 inhibitors have been used since 2013 in the United States by patients with Type 2 diabetes and are also used off-label by Type 1 patients.
Recognizable name brand SGLT-2 inhibitors currently approved for use in patients with Type 2 diabetes include Farxiga, Invokana and Jardiance. In addition to Zynquista, Farxiga (or Forxiga) was recently approved for use in Type 1 diabetes in Europe and Japan.
To learn more about SGLT Inhibitors for use in Type 1 diabetes, click here.
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