Global Study Finds Dapagliflozin Benefits Type 1 Diabetic Patients

The results of the study were published in The Lancet Diabetes & Endocrinology and presented by Dandona, SUNY Distinguished Professor of medicine and chief of endocrinology, diabetes and metabolism, at the annual meeting of the European Association for the Study of Diabetes in Lisbon, Portugal.

Called DEPICT-1, which stands for Dapagliflozin in Patients with Inadequately Controlled Type 1 diabetes, the 24-week study was the first global multicenter investigation of dapagliflozin to test its efficacy and safety in Type 1 diabetes.

The double-blind, randomized, three-arm, phase 3 multicenter study was conducted at 143 sites in 17 countries, including the U.S.

Participants were 833 patients ages 18 to 75 who had inadequately controlled blood sugars with a mean baseline hemoglobin A1C (HbA1c) level of 8.53. A1C levels under seven for Type 1 diabetics are considered optimal.

The results demonstrate that when this drug, a sodium glucose cotransporter-2 inhibitor (SGLT-2) was administered as an adjunct therapy in addition to the insulin that patients with Type 1 diabetes need to survive, it significantly improved outcomes.

“Our paper provides the initial signal that dapagliflozin is safe and effective in patients with Type 1 diabetes and is a promising adjunct treatment to insulin to improve glycemic control,” Dandona says.

“The 24-week results from DEPICT-1 are important as they represent the first Phase 3 trial in Type 1 diabetes of the newer, selective SGLT-2 class of diabetes medicines as an oral adjunct to insulin,” he adds.

In the study, approximately half of the patients taking dapagliflozin reduced their A1C levels by more than 0.5 percent without experiencing severe drops in blood sugar (hypoglycemia).

Dandona explains that any fall in HbA1c of around .5 percent is considered significant and can lead to licensing of a drug as an anti-diabetic agent. He notes, however, that the findings will need further confirmation before the drug can be licensed by the FDA for use in Type 1 diabetes.

“Treating the millions of patients living with Type 1 diabetes while also managing the complications associated with the disease remains a daunting challenge,” says Dandona, who sees patients through UBMD Internal Medicine at the Diabetes-Endocrinology Center of Western New York, which is where the five Buffalo patients in the study were treated.

Dandona is renowned for his diabetes and metabolic research, particularly into new treatments that can be used in addition to insulin, to help patients with Type 1 diabetes achieve better blood sugar control.

He has led the field globally since he published an observational study in 2011 that found that another drug for Type 2 diabetes, liraglutide, could help treat Type 1 diabetes.

“Our key paper in 2011 has led to other drugs being considered for use in Type 1 diabetes,” he says. “We have been pioneers in conceptualizing new ways to help Type 1 diabetes patients achieve better outcomes with new therapies.”

Dandona points out that until these recent developments, there hadn’t been another significant treatment developed for Type 1 diabetes since the discovery of insulin in 1921.

Even Type 1 patients with good glycemic control experience what Dandona calls “glycemic excursions,” pronounced swings from hyperglycemic to hypoglycemic, motivating him and his colleagues to conduct groundbreaking research aimed at discovering non-insulin drugs that can help improve blood sugar control.

In addition, there was no ketoacidosis — an interesting aspect of the current study that is contrary to Dandona’s earlier pilot study with liraglutide and dapagliflozin, in which there were two cases of ketoacidosis in whom the dose of insulin had been reduced by 35 percent from the original baseline.

“We found out that any reduction of insulin dose greater than 20 percent, or the absence of a meal and missing the insulin dose, or the significant intake of alcohol makes you more vulnerable to ketoacidosis,” he explains, noting that since these issues were avoided in the DEPICT-1 study, no increase in ketoacidosis was observed.  

Co-authors on the study are researchers from the following institutions:

• University of Leuven, Belgium
• Schneider Children’s Medical Center of Israel and Sackler Faculty of Medicine, Tel Aviv University, Israel
• Juvenile Diabetes Research Foundation, New York City
• Ruhr University Bochum, Germany

Co-authors also included researchers from AstraZeneca and Bristol-Myers Squibb, the companies that funded the study and partnered to develop dapagliflozin.