Dandona Research Influences European OK of Diabetes Drug

In its announcement in March approving the Type 2 diabetes drug dapagliflozin for adults with Type 1 diabetes when insulin doesn’t provide adequate blood sugar control, the European Commission cited DEPICT-1 and DEPICT-2, randomized clinical trials that demonstrated how it benefits patients with Type 1 diabetes.

Dandona led DEPICT-1 and was the study’s principal investigator and lead author on the paper reporting the trial’s results in The Lancet Diabetes & Endocrinology in September 2017.

“Our pioneering work has led to the licensing of dapagliflozin for Type 1 diabetes in Europe,” Dandona says. “This is a novel oral treatment for Type 1 diabetes, which, when used as an adjunct to insulin, improves the predictability of blood sugar control and provides a real quality of life benefit for patients with the disease.”

Dapagliflozin is marketed under the brand name Forxiga in Europe and Farxiga in the U.S.; it is currently under regulatory review in the U.S. and Japan as an adjunct treatment to insulin for patients with Type 1 diabetes.

For decades, Dandona has been motivated to find new treatments for Type 1 diabetes, which is still addressed with multiple daily infusions of insulin, which, he likes to point out, was discovered nearly a century ago.

He has led the field in exploring potential treatments to use as adjunct therapies with insulin since his published work on another Type 2 diabetes drug, liraglutide, in 2011.

“The sad state of Type 1 diabetics has haunted me since I started my fellowship in endocrinology in the United Kingdom in 1975,” says Dandona, a physician with UBMD Internal Medicine, who also sees patients at the Diabetes-Endocrinology Center of Western New York.

DEPICT-1, which stands for Dapagliflozin in Patients with Inadequately Controlled Type 1 diabetes, was the first global multicenter investigation of dapagliflozin to test its efficacy and safety for 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. It was funded by AstraZeneca and Bristol-Myers Squibb, the companies that partnered to develop dapagliflozin. 

The results demonstrated 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.

In the study, approximately half of the patients taking dapagliflozin reduced their A1C levels by more than .5 of 1 percent without experiencing severe drops in blood sugar (hypoglycemia). Dapagliflozin exerts its plasma glucose-lowering effects by inducing the excretion of glucose in the urine.

Dandona is currently leading a study funded by JDRF — the leading global organization funding Type 1 diabetes research — to determine if dapagliflozin and semaglutide together with insulin would provide a potent “triple therapy” for improving outcomes in Type 1 diabetes. He expects more than 60 percent of patients with Type 1 diabetes to achieve hemoglobin A1c levels below 7 percent.