Dasiglucagon studies show safety for children, adults experiencing severe hypoglycemia
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A next-generation glucagon analog provided rapid and effective treatment of severe hypoglycemia for children and adults with type 1 diabetes, without the need to reconstitute lyophilized powder used in traditional glucagon rescue kits.
“Dasiglucagon provided rapid and effective reversal of hypoglycemia in adults with type 1 diabetes, with safety and tolerability similar to that reported for reconstituted glucagon injection,” Ronnie Aronson, MD, FRCPC, FACE, chief medical officer for LMC Diabetes and Endocrinology in Toronto, told Healio. “The ready-to-use, aqueous formulation of dasiglucagon offers the potential to provide rapid and reliable treatment for severe hypoglycemia. The study showed a reversal of hypoglycemia — with a median recovery time of 10 minutes — with 99% of trial participants reaching recovery within 15 minutes. We know minutes matter in terms of treating severe hypoglycemia, and the findings from this study are very promising.”
Dasiglucagon (Zegalogue, Zealand Pharma), a human glucagon analog, has a unique stability profile in a ready-to-use, aqueous solution, according to the company. As Healio previously reported, the FDA approved dasiglucagon in March as an auto injector or prefilled syringe for the treatment of severe hypoglycemia in people with diabetes aged 6 years and older. The approval of dasiglucagon injection 0.6 mg is based on results from three trials with children and adults with diabetes, which showed a median time to blood glucose recovery from severe hypoglycemia of 10 minutes.
Safety data
Aronson and colleagues analyzed data from 170 adults with type 1 diabetes, each randomly assigned a single subcutaneous dose of 0.6 mg dasiglucagon, placebo or 1 mg reconstituted glucagon during controlled, insulin-induced hypoglycemia. The primary endpoint was time to plasma glucose recovery, defined as an increase of 20 mg/dL from baseline without rescue IV glucose. The primary comparison was dasiglucagon vs. placebo; reconstituted lyophilized glucagon was included as reference.
The median time to recovery was 10 minutes for dasiglucagon compared with 40 minutes for placebo (P < .001); the corresponding result for reconstituted glucagon was 12 minutes.
In the dasiglucagon group, plasma glucose recovery was achieved within 15 minutes in all but one participant, superior to placebo (99% vs 2%; P < .001) and similar to glucagon (95%). Similar outcomes were observed for the other investigated time points at 10, 20, and 30 minutes after dosing. The findings were published in Diabetes Care.
In a second study published in Pediatric Diabetes, Tadej Battelino, MD, PhD, professor of pediatrics and the head of department of pediatric endocrinology, diabetes and metabolism at University Children’s Hospital Ljubljana in Slovenia, and colleagues randomly assigned 42 children and adolescents aged 6 to 17 years a single subcutaneous 0.6 mg injection of dasiglucagon, placebo or reconstituted glucagon, also during insulin-induced hypoglycemia. The primary endpoint was time to plasma glucose recovery, defined as the first plasma glucose of at least 20 mg/dL after treatment initiation without rescue IV glucose. The primary comparison was dasiglucagon vs placebo; glucagon acted as a reference.
For that study, median time to glucose recovery after injection was 10 minutes for dasiglucagon vs. 30 minutes for placebo (P < .001); the median time for glucagon was 10 minutes, which did not include the time taken to reconstitute the lyophilized powder. Glucose recovery was achieved among all participants in the dasiglucagon and glucagon groups within 20 minutes of dosing compared with two of 11 patients (18%) with placebo. For both studies, the most frequent adverse effects were nausea and vomiting, which are known complications of glucagon treatment.
Advantages of rescue pen
“Existing injectable glucagon products require mixing a powdered glucagon product with diluent, drawing up in a syringe and then injecting,” Aronson told Healio. “Even among trained caregivers, the process has had documented obstacles in complexity, leading to administration delays with a mean delivery time of 2.5 minutes. Simulation studies have found that even up to 88% of the time, the dose isn’t delivered fully, or at all.”
Aronson said a syringe or injector device, prefilled with a stable glucagon product like dasiglucagon, has the potential of removing the legacy obstacles of earlier glucagon products.
“People with diabetes and their caregivers will be more likely to fill their prescriptions and deliver a dose with more confidence and accuracy, in these stressful urgent situations,” Aronson said. “The potential benefits are less calls to emergency medical services, less hospitalization, resulting in reduced health care costs and improved quality of life for these individuals.”
Reference:
For more information:
Ronnie Aronson, MD, FRCPC, FACE, can be reached at ronnie.aronson@lmc.ca.
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