New data show dasiglucagon a reliable and rapid treatment in restoring plasma glucose levels.
The need for proper treatment of severe hypoglycemia in patients with diabetes led to the development of dasiglucagon, a ready-to-use aqueous glucagon analog formulation.
Now, new data from investigators,led by Tadej Battelino, MD, of the University Children’s Hospital in Ljubljana, Slovenia, found that dasiglucagon had a rapid, effective response in restoring plasma glucose (PG) levels after insulin-induced hypoglycemia in children with type 1 diabetes (T1D).
The team evaluated the safety and efficacy in a group of pediatric individuals with T1D, aged 6 – 17 years old.
Incidence rates of severe hypoglycemia have reduced in recent years due to increased education and monitoring tools, investigators wrote. However, multiple hypoglycemic episodes could have negative cognitive effects, particularly in children.
Glucagon treatment often require reconstitution of the drug product, which creates a barrier in the timely administration of the treatment. Other developments do not require reconstruction, including subcutaneous (SC) injection or lyophilized nasal powder.
The team investigated dasiglucagon as an alternative treatment, which uses a continuous infusion SC pump delivery for patients with severe hypoglycemia.
Investigators used a multicenter, randomized, placebo-controlled, double-blind, parallel group trial design for the phase 3 assessment.
The study found children and adolescents with T1D at 5 sites in Germany, Slovenia, and the United States, between September 2018 – June 2019.
The team randomly allocated participants 2:1:1 to receive a single SC injection of 0.6 mg dasiglucagon, placebo, or reconstituted glucagon.
Participants were required to have been diagnosed with T1D for at least 1 years prior to trial, receiving daily insulin, and ≥20 kg in body weight.
Investigators had participants attend an on-site dosing visit. Hypoglycemia was induced through intravenous (IV) infusion of insulin glulisine (100 U/mL).
Infusion was stopped once the PG concentration was <80 mg/dL (4.4 mmol/L). If PG was ≥54 mg/dL, the study drug was administered by the SC injection.
The team’s primary endpoint was time from dosing to PG recovery. They defined the endpoint as time to first observed increase in PG of ≥20 mg/dL (1.1 mmol/L) from the baseline without IV glucose rescue treatment.
The PG was considered not recovered if IV glucose was administered prior to recovery, or recovery was not achieved by 45 minutes.
The trial screened 59 children and adolescents, with 41 eligible participants assigned dasiglucagon (n = 20), placebo (n = 11), glucagon (n = 10). All completed the trial.
Investigators found dasiglucagon was superior in comparison to the placebo in the primary endpoint of time from dosing to PG recovery.
Dasiglucagon had an estimated median of 10 minutes (95% CI, 8 – 12), while the placebo had a median of 30 minutes (95% CI, 20, upper limit not estimated; all P <.001).
The median in the glucagon group had a PG recovery time of 10 minutes (95% CI, 8 – 12).
Investigators found all participants but 1 in the dasiglucagon experienced PG recovery by 15 minutes, with all having PG recovery by 20 minutes.
In contrast, the team found no participant had PG recovery with placebo by 15 minutes, 2 had PG recovery by 20 minutes, and 4 had PG recovery over 45 minutes.
The most common adverse effects for dasiglucagon and glucagon were nausea and vomiting, particularly within 1.5 – 3 hours of dosing.
Investigators concluded that dasiglucagon is an effective, reliable treatment in restoring PG levels following insulin-induced hypoglycemia in children and adolescents with T1D.
The dasiglucsagon treatment was well tolerated, with the adverse effects expected from known safety profile of glucagon treatment.
“These findings are in line with results for dasiglucagon trials in adults, supporting the use of a common SC dose of dasiglucagon (0.6 mg) to treat severe hypoglycemia in pediatric (6 - 17 years) and adult individuals with diabetes,” investigators wrote.
The study, “Dasiglucagon, a next-generation ready-to-use glucagon analog, for treatment of severe hypoglycemia in children and adolescents with type 1 diabetes: results of a phase 3, randomized controlled trial,” was published online in Diabetes Care.