Intranasal Glucagon Effective for Hypoglycemia in Type 1 Diabetes

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Intranasal glucagon was effective in treating insulin-induced hypoglycemia in type 1 diabetes.

When compared with intramuscular glucagon, intranasal glucagon was effective in treating insulin-induced hypoglycemia in patients with type 1 diabetes, according to data published in Diabetes Care.

Patients with insulin-dependent diabetes are prone to episodes of severe hypoglycemia caused by an excess of insulin. While glucagon counteracts how insulin lowers glucose, it is only available as a dry powder that is dissolved in a syringe before intramuscular injection, noted study researcher Michael R Rickels, MD, MS, associate professor of medicine at the University of Pennsylvania Perelman School of Medicine in Philadelphia.

“This process is prone to error or omission at times of emergency, leaving patients susceptible to prolonged periods of dangerously low blood glucose while awaiting emergency medical services,” Dr Rickels told Endocrinology Advisor.

For their study, Dr Rickels and colleagues evaluated 75 patients with type 1 diabetes (mean age, 33 years) at 8 clinical centers. Patients were given insulin to induce hypoglycemia and randomly assigned to receive intramuscular glucagon (1 mg) or intranasal glucagon (3 mg).

Needle-free intranasal glucagon was “discharged by a single-step device delivering a dry powder formulation that is absorbed across the nasal mucosa without any requirement for inhalation or other cooperation from the patient,” explained Dr Rickels.

“The intranasal glucagon preparation was effective in increasing the plasma glucose to ≥70 mg/dL or ≥20 mg/dL from the lowest glucose value within 30 minutes of administration (success), meeting the prespecified criteria for noninferiority in comparison to intramuscular glucagon,” Dr Rickels said.

Success criteria were met in 98.7% of intranasal glucagon visits and 100% of intramuscular glucagon visits.

“There was a delay of a few minutes in the initial glucose-raising response to intranasal glucagon, and more head and facial discomfort reported, although only during a quarter of the intranasal visits,” he added.

Specifically, the mean time to success was 16 minutes for patients in the intranasal group and 13 minutes in the intramuscular group (P<.001), according to the data.

Patients reported head or facial discomfort during 25% of intranasal visits as well as nausea with or without vomiting during 35% of intranasal visits.

For patients in the intramuscular group, head or facial discomfort was reported during 9% of visits, and nausea with or without vomiting occurred during 28% of visits.

Despite these complications, Dr Rickels said that intranasal glucagon delivery is a promising new approach to correct severe hypoglycemia in patients with diabetes treated with insulin.

“These differences should not affect intranasal glucagon being highly effective in treating insulin-induced hypoglycemia since it eliminates the time required for reconstitution of injectable glucagon would be used in patients with impaired consciousness,” he said.


  1. Rickels M, Ruedy K, Foster N, et al. Intranasal Glucagon for Treatment of Insulin-Induced Hypoglycemia in Adults With Type 1 Diabetes: A Randomized Crossover Noninferiority Study. Diabetes Care. 2015;doi: 10.2337/dc15-1498.