BERLIN – A dry-powder nasal formulation of glucagon was as good as intramuscular delivery for the reversal of severe hypoglycemia in patients with type 1 diabetes mellitus (T1DM) in a randomized controlled trial.
A 100% treatment success rate (n = 66) was seen for both nasal glucagon and intramuscular glucagon, defined as an increase in plasma glucose to 70 mg/dL (3.9 mmol/L or greater) or more or an increase of 20 mg/L (1.1 mmol/L) or more from the glucose nadir within 30 minutes of administration.
Furthermore, slightly more than 97% of patients achieved treatment success within 15 minutes in both treatment groups, with mean times of 11.4 minutes for the nasal formulation and 9.8 minutes for intramuscular administration.
Similar glucose responses were observed within 40 minutes of glucagon administration, study investigatorreported at the annual meeting of the European Association for the Study of Diabetes. Dr. Plum-Mörschel is the CEO of the clinical research organization Profil Mainz (Germany), which helped Eli Lilly conduct the trial.
“We are all aware and fully agree that severe hypoglycemia is a serious and potentially life-threatening complication of diabetes treatment with insulin and the sulfonylureas,” said Dr. Plum-Mörschel. At least one in three patients with diabetes reports one hypoglycemic episode per year, she added. While this is quite prevalent in patients with T1DM, it’s not uncommon for those with type 2 diabetes mellitus (T2DM) to experience hypoglycemic episodes.
“Outside of a hospital or emergency room setting, injectable glucagon is currently the only option to treat severe hypoglycemia,” Dr. Plum-Mörschel reminded delegates. “Thankfully, the available injectable glucagon emergency kits are highly effective for the treatment of hypoglycemic events,” she added.
However, for untrained caregivers they can be “really challenging to use,” according to Dr. Plum-Mörschel. This is because the available kits involve multiple steps, including reconstitution, before being ready to inject. A severe hypoglycemic event is stressful enough without them worrying about getting things right, she suggested.
This is where a nasal formulation would be advantageous, and it is something that’s been touted to be on the horizon for a few years. Studies have previously shown that nasal glucagon is comparable to intramuscular glucagon in both adult and pediatric populations. Turning the formulation used in those studies into a commercial product however, has meant more clinical testing before being licensed by the regulatory authorities.
The nasal formulation consists of a dry power containing 3 mg glucagon that is provided in a single-use, compact, and thus, portable, device. It’s been designed to be stored at room temperature and is ready to use immediately. Pressing the plunger on the device releases the fine powder that does not require inhalation to work, which means it can be given easily to an unconscious patient with severe hypoglycemia.
“The aim of thewas to compare the efficacy and safety of commercially manufactured nasal glucagon with intramuscular glucagon for the treatment of insulin-induced hypoglycemia in adults with type 1 diabetes,” Dr. Plum-Mörschel said.
It was a randomized, single-dose, crossover study involving 70 adult patients with T1DM with hypoglycemia artificially induced by an intravenous insulin infusion during the two dosing visits. Five minutes after stopping insulin, nasal glucagon (3 mg) or intramuscular (1 mg) was given, with multiple plasma glucose measurements taken for up to 90 minutes.
The mean age of participants was 41.7 years old, 61% were male, the mean duration of diabetes was 19.8 years, with a baseline glycated hemoglobin (HbA1c) of 7.3%.
As for safety, Dr. Plum-Mörschel noted that nasal glucagon had a safety profile that was acceptable for emergency treatment. There was no difference between the nasal or intramuscular glucagon treatment groups in the percentages of patients experiencing treatment-emergent adverse events (at least 5% frequency): nausea was seen in 22% and 29%, vomiting in 10% and 12%, and headache in 12% and 7%, respectively.
Asking patients who had been treated with nasal glucagon about specific symptoms related to nasal administration showed around 63% had watery eyes, 49% nasal itching, 39% nasal congestion, 37% a runny nose, 24% sneezing, 20% itchy eyes, and 12.9% itchy throat. “All of these events were transient, generally mild or moderate in nature, and none were serious. Indeed, there were no deaths in the study and no other serious AEs [adverse events] occurred.”
Dr. Plum-Mörschel concluded: “These results support nasal glucagon as a viable alternative to intramuscular glucagon for the treatment of severe hypoglycemia.
“I personally would expect that, due to its simplicity of use, nasal glucagon will create a greater community who can render quick aid in a rescue situation.”
The study was funded by Eli Lilly. Dr. Plum-Mörschel is an employee of Profil Mainz and has received travel grants and speaker honoraria from Eli Lilly and Novo Nordisk.
SOURCE: Suico J et al. EASD 2018, .