Zynquista Pill Approved for Adults with Type 1 Diabetes in Europe

By Emma Ryan and Ann Carracher

The EMA approved Zynquista (sotagliflozin), an SGLT-1/2 dual inhibitor, for adults with a BMI above 27

The European Medicines Agency (EMA) recently approved Zynquista, a once-a-day glucose lowering pill, for people with type 1 diabetes and a BMI (body mass index) above 27. Zynquista, has been shown to lower blood glucose, reduce the amount of insulin needed, and result in weight loss. Zynquista joins Forxiga as the first “adjunct” (added to insulin) pills for people with type 1 diabetes in Europe. (Read about Forxiga’s approval here.)

Results from the inTandem drug trials showed that compared to placebo (a “nothing” pill) people with type 1 diabetes taking Zynquista:

• Reduced A1C by 0.25% from an average starting A1C of 7.6%,

• Increased time in range (70-180 mg/dl) by 1.3 hours per day,

• Lost about 5 pounds from an average starting weight of 192 pounds, and

• Decreased their total daily insulin dose by 4%, or about two units.

As a dual SGLT-1/2 inhibitor, Zynquista works in two ways: the SGLT-1 inhibitor delays and reduces glucose from being absorbed by the intestines, and the SGLT-2 inhibitor allows glucose to be excreted through the urine – independently of insulin.

SGLT-2 inhibitors pose an increased risk for a type of DKA (known as ‘euglycemic DKA’) because when you use these drugs, insulin doses are generally lower. If insulin levels get too low, however, the body breaks down fat for energy, leading to an accumulation of ketones. While having some ketones in the blood is not harmful – e.g., ketones that appear in low-carb diets – sustained high ketone levels can result in DKA. Learn more about ketones here.  See our infographic on strategies to reduce risk for DKA here. The EMA is limiting use to people with a BMI over 27 because evidence suggests that individuals at this body weight may be at a lower risk of DKA.

In the United States, the FDA has decided not to approve Zynquista or Farxiga for people with type 1 diabetes at this stage. Though FDA did not discuss their approach or reasons publicly, we are hopeful that FDA approval is possible in the future. Lexicon and Sanofi, the manufacturers of Zynquista, and AstraZeneca, the manufacturer of Farxiga, are currently seeking meetings with the FDA to determine next steps.

Two other SGLT-2 inhibitors, Jardiance and Invokana, are only available for people with type 2 diabetes in both the US and Europe.