麻豆传媒

ORLANDO -- Patients with poorly controlled type 1 diabetes appeared to get better glycemic control and lose weight when treated with dapagliflozin (Farxiga) as an add-on agent to insulin, according to a study presented here.

The phase III DEPICT-2 trial examined 6-month outcomes of adjustable insulin plus placebo or 5-mg or 10-mg doses of dapagliflozin. Patients on the sodium-glucose co-transporter-2 (SGLT2) inhibitor saw their HbA1c levels reduced by 0.37% or 0.42%, respectively, and lost 3.2 or 3.7 kg of body weight, reported Chantal Mathieu, MD, PhD, of the Catholic University of Leuven, Belgium.

"Introduction of dapagliflozin as an adjunct therapy could be an interesting and exciting new treatment for type 1 diabetes, almost 100 years after the discovery of life-saving insulin," said Mathieu during a press conference at the American Diabetes Association annual meeting. "However, adding dapagliflozin to the insulin regimen needs to be balanced against the increased risk of diabetic ketoacidosis, and this therapy should be coupled with intensive educational measures to cope with the small, but real risks."

There were no episodes of diabetic ketoacidosis among the placebo patients, but 2.6% of patients on the 5 mg dose of dapagliflozin and 2.2% of patients on the 10 mg dose experienced the potentially life-threatening condition, the researchers reported.

In commenting on the study, press conference moderator Bernard Zinman, MD, of the University of Toronto, told 麻豆传媒 that the incidence of diabetic ketoacidosis with use of dapagliflozin needed further examination.

"There needs to be restricted access to these SGLT2 agents by people with type 1 diabetes," he said. "We need to be very selective of who prescribes these drugs and to whom they are prescribed. People are going to have to be able to monitor ketones on their own."

In the study, at 24 weeks, the 271 patients assigned to dapagliflozin 5 mg daily achieved a 0.37% decline in HbA1c; the 270 patients assigned to dapagliflozin 10 mg daily achieved a 0.42% decline in HbA1c; the 272 patients assigned to placebo had no improvement in HbA1c (P<0.0001). All patients were on optimized insulin therapy.

"Results of the DEPICT-2 study were consistent with those of its twin study, DEPICT-1, which followed mostly European and American patients with type 1 diabetes," Mathieu said. Roughly a quarter of patients on DEPICT-2 were from Asia.

Mathieu suggested that dapagliflozin could help fill an unmet medical need for type 1 diabetics: improved HbA1c without weight gain and hypoglycemia -- which can be fatal among persons using insulin -- and with more stable glucose profiles.

"The results of our study add to a growing body of evidence showing that SGLT2 inhibitors have the potential to serve as promising adjunct therapies in people with type 1 diabetes who are not consistently in their target blood glucose range," she said.

In the 24-week interim analysis of the 52-week study, patients on the 5 mg dose of dapagliflozin lost an average of 3.4 kg and patients on the 10 mg dose lost 3.74 kg compared with a negligible change in body weight among patients who were on placebo (P<0.0001).

Patients on the 5 mg dose of dapagliflozin reduced their insulin requirements by 10.78% and those on the 10 mg dose reduced their insulin by 11.08% over the course of the study, while placebo patients increased their insulin dose by about 2% (P<0.0001).

In the secondary outcome composite measure of clinical benefit -- a ≥0.5% reduction in HbA1c without severe hypoglycemia -- 39.5% of patients on the 5 mg dose of dapagliflozin achieved this milestone, along with 41.6% of patients on the 10 mg dose, compared with 20.1% of patients on placebo (P<0.0001).

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