The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended an additional indication for dapagliflozin (Forxiga/Farxiga/Edistride, AstraZeneca) for use in adults with type 1 diabetes who meet certain criteria.
The drug, a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor, is already approved for use in type 2 diabetes in the European Union, United States, and elsewhere.
If given the okay for this new use in the European Union, usually a formality, dapagliflozin would be the first oral add-on treatment to insulin for type 1 diabetes anywhere in the world.
To mitigate the risk for diabetic ketoacidosis (DKA) among patients with type 1 diabetes in trials of several different SGLT2 inhibitors, the proposed EU indication limits dapagliflozin's use to patients with type 1 diabetes with a body mass index of 27 kg/m2 or higher who aren't meeting glycemic goals despite high insulin doses.
Insulin doses would need to be continuously optimized during dapagliflozin treatment by a diabetes specialist and only reduced to avoid hypoglycemia.
And patients would need to be instructed to control ketone levels and recognize risk factors and signs and symptoms of DKA.
The CHMP positive opinion was based on data from two phase 3 clinical trials from the DEPICT (Dapagliflozin Evaluation in Patients With Inadequately Controlled Type 1 Diabetes) clinical program.
As previously reported by Medscape Medical News, both DEPICT-1 and DEPICT-2 were 24-week randomized, double-blinded trials with long-term extensions up to 52 weeks and each included about 800 patients. In both trials, significant reductions in HbA1c (the primary endpoint), weight, and total daily insulin dose were achieved with both 5-mg and 10-mg doses of dapagliflozin.
Rates of DKA were about equal across groups in DEPICT-1, occurring in 1% to 2% of the dapagliflozin and placebo groups. In DEPICT-2, there was a small but significant increase in DKA with the drug, up to 2.6% with the 10-mg dose, versus no cases with placebo.
But many experts worry that the risk for DKA may be much greater if such agents are used under real-world conditions, without the close monitoring performed in clinical trials.
That concern was expressed at a recent US Food and Drug Administration advisory panel meeting for sotagliflozin (Sanofi/Lexicon), a dual SGLT1 and SGLT2 inhibitor.
That panel vote was split down the middle, 8-8, on whether the benefits outweigh the risks for the drug as an add-on for type 1 diabetes, and even those who voted in favor did so with strong recommendations for DKA risk mitigation. Some advised that the company provide ketone testing kits for patients along with the medication.
An FDA decision on approval of sotagliflozin is expected by the end of March.
Dapagliflozin is currently under regulatory review in both the United States and Japan for use as adjunct treatment to insulin in adults with type 1 diabetes.
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Cite this: EU Panel Backs Dapagliflozin for Some With Type 1 Diabetes - Medscape - Feb 01, 2019.
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