An Important Step in the FDA Review of Sotagliflozin (Zynquista™) for T1D

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You’ll hear it again and again: For some people with type 1 diabetes (T1D), SGLT inhibitor therapy* means taking less insulin, having increased time in range, reducing the minute-to-minute glucose variability, contributing to weight loss and lowering your A1c. But you’ll also hear about the risks. From dehydration and constant urination to urinary tract infections to the more dangerous diabetic ketoacidosis (DKA).


DKA is a life-threatening complication that happens when there isn’t enough insulin in the body. This is usually found in people whose blood sugar is very high. But with SGLT inhibitor therapy, many who experience DKA present with only slightly elevated blood-sugar levels (a condition referred to as euglycemic DKA), making it hard to recognize and treat. This is because people on an SGLT inhibitor are urinating out the glucose. Because of this, people with T1D on an SGLT inhibitor need to do ketone testing (ketoacidosis is an abundance of ketones in the blood). When elevated ketones are present in the blood (or urine), people have to inject insulin and consume carbohydrates, in order to avoid DKA and potential hospitalization—even if their blood-sugar levels are normal or near it.


The Food and Drug Administration (FDA) heard from its Endocrinologic and Metabolic Drugs Advisory Committee about SGLT inhibitors yesterday, as part of its review of sotagliflozin (Zynquista™), which has been submitted to the FDA for approval for T1D, for use in combination with insulin to improve blood-sugar control. The Advisory Committee spent the day hearing about sotagliflozin (Zynquista™)—its benefits, the risk of DKA, and the sponsor’s plan for DKA risk mitigation. What the Committee members were asked: Do the benefits outweigh the risks?

At the end of it, the Advisory Committee voted 8-8: 8 supported sotagliflozin approval, and 8 did not. The FDA will take all of the input provided by the Committee into account when it makes a decision, targeted for the end of March, about approval of the drug.

FDA and Committee members also heard from the public as part of the meeting. Sanjoy Dutta, Ph.D., presented JDRF’s remarks, emphasizing the unmet need in T1D for therapy options in addition to insulin, the potential benefits of SGLT inhibitors and the importance of a mitigation plan for the risk of DKA. Many individuals with T1D who had participated in the clinical trials of the drug also relayed their positive experiences to the FDA and the Advisory Committee.

If it is approved, it will be only the third drug for T1D (the first two are insulin and a drug called pramlintide). It has been almost 15 years since a drug has been approved for this condition and would be the only oral drug approved for this disease. Sotagliflozin (Zynquista™) has also been submitted in Europe for approval for T1D.


There are currently four SGLT inhibitors that have been FDA approved for type 2 diabetes:

  • dapagliflozin (Farxiga®/Forxiga®) (which has also been submitted in Europe for approval for T1D)
  • canagliflozin (Invokana®)
  • empagliflozin (Jardiance®)
  • ertugliflozin (Steglatro™)

It should be noted that a paper recently published in Diabetes Care summarizes an international consensus, which provides recommendations for the safe use of SGLT inhibitors in people with T1D. SGLT inhibitors, say the authors, demonstrate significant benefits for people with T1D, including improved blood-sugar control, increased time in range and weight loss, but “strategies for mitigating DKA risk are vital to the adoption and safe use” of these drugs.

JDRF was critical in fostering the drug development process for sotagliflozin (Zynquista™). JDRF was one of the first to support a clinical trial to see if it worked in T1D. In this and later clinical trials, the drug showed a significant reduction in blood-sugar levels, and also improved other key health measures.

As we heard yesterday, if it is FDA approved, this drug won’t be for everyone with T1D because of the DKA risk, but nonetheless, it will be a big win for the T1D community, giving them another possible tool in their diabetes management, which has been a longtime coming.

*It should be noted that these are taken, for the most part, off label.

By Alexandra Mulvey