This is the second agency rejection of a sodium-glucose co-transporter (SGLT) inhibitor for the treatment of type 1 diabetes that cannot be controlled by insulin.

Farxiga (dapagliflozin) is a blockbuster drug from AstraZeneca (AZ) for the treatment of type 2 diabetes. Farxiga is a member of the gliflozin class of sodium-glucose cotransporter-2 (SGLT2) inhibitors that, when combined with diet and exercise, lower blood sugar levels.

AZ was hoping to get Farxiga also approved for the treatment of type 1 diabetes in the United States, given that the European Medicines Agency (EMA) granted marketing authorization for this indication in March 2019.

The U.S. Food and Drug Administration (FDA), however, is concerned about the safety of SGLT inhibitors when given to type 1 diabetes patients. It has now rejected applications for Farxiga and Zynquista (sotagliflozin) from Sanofi and Lexicon over concerns about higher rates of diabetic ketoacidosis (DKA) associated with the use of these drugs. DKA can be hard to detect in type 1 diabetes patients, and therefore these patients do not know to take insulin and consume carbs and can end up requiring hospitalization.

AZ had included a safety program involving frequent determination of ketone levels that indicate DKA. The EMA was satisfied with the data, including evidence of weight loss, A1c control and lower insulin use.