medwireNews: Dapagliflozin is a promising adjunct treatment to insulin for patients with type 1 diabetes, suggest phase III trial results presented at the EASD annual meeting in Lisbon, Portugal, and published simultaneously in The Lancet Diabetes & Endocrinology.
The DEPICT-1 (Dapagliflozin Evaluation in Patients With Inadequately Controlled Type 1 Diabetes) investigators found that insulin-treated patients with inadequately controlled diabetes who were randomly assigned to receive the sodium–glucose cotransporter-2 (SGLT2) inhibitor at a dose of 5 mg (n=277) or 10 mg (n=296) once daily experienced a mean reduction in glycated hemoglobin (HbA1c) levels from 8.5% at the time of randomization to approximately 8.0% at week 24.
By comparison, HbA1c levels among the 260 patients who received placebo alongside insulin therapy remained consistent at around 8.5% throughout the study.
We have known for a long time that insulin alone is not sufficient for many of our patients
These findings translate into a significant 0.42% greater decrease in HbA1c levels for patients receiving dapagliflozin 5 mg compared with placebo, and a significant 0.45% greater decrease for those receiving the 10 mg dose relative to placebo, report Paresh Dandona (State University of New York at Buffalo, USA) and study co-authors.
Furthermore, participants receiving dapagliflozin at either dose had significant reductions in total daily insulin dose and in bodyweight over the study period compared with placebo-treated patients.
The most commonly reported adverse event was nasopharyngitis, experienced by 14%, 12%, and 15% of patients in the 5 mg, 10 mg, and placebo groups, respectively, followed by urinary tract infection, upper respiratory tract infection, and headache.
Most adverse events were mild or moderate in intensity, and rates of hypoglycemia and severe hypoglycemia were comparable across the groups.
“The overall adverse event profile was similar to clinical study experience with dapagliflozin in patients with type 2 diabetes,” summarize Dandona and colleagues.
They note that “[d]iabetic ketoacidosis is a recognised risk in type 1 diabetes, and reductions in insulin dose associated with the use of SGLT2 inhibitors have been linked to diabetic ketoacidosis,” and therefore insulin dose was reduced by a maximum of 20% over the study period to avoid ketoacidosis while reducing the risk for hypoglycemia. Patients were also given blood ketone monitors and advised on how to identify potential symptoms of ketoacidosis.
In all, 1.4% of participants in the 5 mg dapagliflozin group, 1.7% of those in the 10 mg group, and 1.2% of patients receiving placebo experienced definite ketoacidosis over the study period, and “[a] small increase in ketone-related events seen with dapagliflozin was manageable with standard care,” say the researchers.
Summing up the DEPICT-1 results, Dandona told delegates at the EASD meeting that “dapagliflozin is the first selective SGLT2 inhibitor to demonstrate a significant reduction in HbAc through 24 weeks when used as an adjunct to adjustable insulin for the treatment of type 1 diabetes at doses of 5 and 10 mg daily.”
He believes that “based on this 24-week study, dapagliflozin may be considered a good candidate as an adjunct to insulin to improve glycemic control.”
The study commentator Maciej Malecki (University Hospital, Krakow, Poland) agreed, telling the audience that the “DEPICT-1 study results give hope for a prompt registration of dapagliflozin as adjunct therapy” for type 1 diabetes.
And Malecki concluded that “further post-registration observations will be required to fully define its safety profile in type 1 diabetes.”
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