1. Grant, Joan S. PhD, RN
  2. Graven, Lucinda J. PhD, MSN, ARNP

Article Content

Q: I understand there is a new intranasal glucagon to treat hypoglycemia being released in the near future. Is it as effective as injectable glucagon? What other information should I know about this agent?


Approximately 6 million or nearly 29% of individuals with diabetes mellitus take insulin, either alone or in conjunction with oral glucose-lowering agents, to control their diabetes mellitus. Unfortunately, severe hypoglycemia is a complication associated with insulin administration. In 2011, hypoglycemia accounted for approximately 282,000 emergency department visits by adults with diabetes (Centers for Disease Control and Prevention, 2014). Glucagon is a hormone that stimulates the liver to release stored glucose. However, reconstituting and administrating injectable glucagon for hypoglycemia to either uncooperative or unconscious individuals can be stressful and lead to medication errors by caregivers in the home.


In addressing this issue, Eli Lilly and Company (2015) announced worldwide rights to a dry mist intranasal glucagon developed by Locemia Solutions (2016) that is in Phase III trials. Intranasal glucagon uses a proprietary glucagon nasal powder formulation that is delivered using a single-use, ready-to-use device. This dry power does not need to be inhaled but rather, pushing the base of the container ejects (with a semiloud click sound) the dry powder of glucagon into nasal passages, where it is directly absorbed (Eli Lilly and Company; Locemia Solutions). Nasal congestion does not affect glucagon absorption or medication pharmacokinetics (Tucker, 2015). Although current studies have focused on adults and children with type 1 diabetes mellitus who take insulin, intranasal glucagon could be potentially useful for individuals with type 2 diabetes who take either insulin or sulfonylureas (Tucker). The product's safety in pregnancy is unknown.


Based upon study findings, the suggested dosage for both children (i.e., 4 to 16 years; Sherr et al., 2016) and adults (Rickels et al., 2016) is a single 3 mg dose of intranasal glucagon. A second dose of the medication can be administered, if necessary, to treat the hypoglycemia (Boido et al., 2015). Side effects for intranasal glucagon when compared with injectable glucagon vary among age-groups. Although adults report significantly more transient nasal and head/facial discomfort (Rickels et al.), children have no significant differences in facial discomfort (Sherr et al.) with intranasal glucagon. The presence of nausea and vomiting are comparable for those receiving either the intranasal or injectable glucagon (Rickels et al.; Sherr et al.).


In examining its use in adults, a randomized trial of 75 individuals with type 1 diabetes mellitus (mean age, 33 +/-12 years) compared use of intranasal (3 mg) and intramuscular (1 mg) glucagon for treatment of hypoglycemia. The average time for raising plasma glucose to >=70 mg/dL or >=20 mg/dL was 16 and 13 minutes, respectively, for those receiving intranasal and intramuscular agents (Rickels et al., 2016). Furthermore, in a meta-analysis of studies comparing glucose with different glucagon formulations, data indicate glucagon failure rates are few (and similar to dextrose) and that intramuscular and intranasal glucagon are comparable (Boido et al., 2015).


In a study examining the use of intranasal glucagon in children, 48 children (i.e., 4 to 16 years) randomly received either intranasal (i.e., 2 or 3 mg) or intramuscular glucagon (i.e., 1 mg or based upon weight) for hypoglycemia. All participants receiving intramuscular doses and all except one participant receiving the intranasal doses responded with a >=25 mg/dL rise in glucose within 20 minutes of dosing and times to peak plasma glucose and glucagon levels were similar for both groups. The participant who failed to have a comparable rise in plasma glucose blew their nose immediately after receiving the intranasal glucagon, but reached a plasma glucose of 65 mg/dL after 30 minutes and had an increase of 25 mg/dL in plasma glucose after 40 minutes. Hence, these study results supported the potential efficacy of glucagon nasal powder for treatment of hypoglycemia in youth with type 1 diabetes (Sherr et al., 2016).


Data regarding the usefulness of intranasal glucagon administered by family members in the home rather than trained professionals are limited and further research is needed. However, in one study, 16 trained caregivers showed a low success rate and numerous errors (14 out of 16) in giving injectable glucagon, compared with a high success rate (15 out of 16) in correctly giving the intranasal glucagon to manikins (Yale et al., 2015).


Home healthcare clinicians should teach principles of good diabetes management and educate patients and family on the signs and symptoms of hypoglycemia, which include shakiness, anxiety, sweating, and headache. Assessing capillary glucoses levels before and after meals and at bedtime and when these signs and symptoms first occur is important (American Diabetes Association, 2016). Likewise, education should be provided on proper administration of the intranasal device in order to ensure that the medication is properly dispensed. Correct administration involves placing the tip of the device into one of the patient's nostrils and depressing the plunger connected to a piston that discharges the powder. Glucagon absorption then occurs through the nasal mucosa (Tucker, 2015). As always, caregivers should call for emergency assistance if the glucagon is ineffective in treating the hypoglycemia.


Difference in price between injectable and intranasal glucagon is unclear at this time. The potential for higher sales of intranasal glucagon because of its ease of use may potentially provide cost savings. There also is a potential for companies who sell injectable glucagon to provide more cost savings once the intranasal glucagon becomes available for those starting or already taking injectable glucagon.




American Diabetes Association. (2016). Hypoglycemia. Retrieved from[Context Link]


Boido A., Ceriani V., Pontiroli A. E. (2015). Glucagon for hypoglycemic episodes in insulin-treated diabetic patients: A systematic review and meta-analysis with a comparison of glucagon with dextrose and of different glucagon formulations. Acta Diabetologica, 52(2), 405-412. doi:10.1007/s00592-014-0665-0 [Context Link]


Centers for Disease Control and Prevention. (2014). National Diabetes Statistics Report: Estimates of Diabetes and its Burden in the United States, 2014. Atlanta, GA: U.S. Department of Health and Human Services. [Context Link]


Eli Lilly and Company. (2015). Lilly acquires phase III intranasal glucagon from Locemia Solutions. Retrieved from[Context Link]


Locemia Solutions. (2016). Developing a solution: Phase 3 trials are underway. Retrieved from[Context Link]


Rickels M. R., Ruedy K. J., Foster N. C., Piche C. A., Dulude H., Sherr J. L., ...T1D Exchange Intranasal Glucagon Investigators. (2016). Intranasal glucagon for treatment of insulin-induced hypoglycemia in adults with type 1 diabetes: A randomized crossover noninferiority study. Diabetes Care, 39, 264-270. doi:10.2337/dc15-1498 [Context Link]


Sherr J. L., Ruedy K. J., Foster N. C., Piche C. A., Dulude H., Rickels M. R., ...T1D Exchange Intranasal Glucagon Investigators(2016). Glucagon nasal powder: A promising alternative to intramuscular glucagon in youth with type 1 Diabetes. Diabetes Care, 39(4), 555-562. doi:10.2337/dc15-1606 [Context Link]


Tucker M. E. (2015). Intranasal glucagon combats hypoglycemia in type I diabetes. Retrieved from[Context Link]


Yale J., Dissinger E., Dulude H., Egeth M., Fink N., Lafontaine M., ..., Shames A. (2015). Needle-free nasal delivery of glucagon is superior to injectable delivery in simulated hypoglycemia rescue. E-poster #867. Retrieved from[Context Link]