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FOCUS ON
DIABETES
Intranasal Glucagon for Severe Hypoglycemia
JOAN S. GRANT, PHD, RN, AND LUCINDA J. GRAVEN, PHD, MSN, ARNP
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
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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 metaanalysis 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/
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Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.
© FangXiaNuo / iStock
Joan S. Grant, PhD, RN, is a Professor,
School of Nursing, University of Alabama at
Birmingham, Birmingham, Alabama.
Lucinda J. Graven, PhD, MSN, ARNP, is
an Assistant Professor, College of Nursing,
Florida State University, Tallahassee, Florida.
The authors declare no conflicts of interest.
Address for correspondence: Joan S. Grant,
PhD, RN, University of Alabama at Birmingham School of Nursing, 1701 University Blvd.,
Birmingham, AL 35294-1210 (grantj@uab.edu).
In 2011, hypoglycemia accounted for approximately
282,000 emergency department visits by adults
with diabetes.
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
February 2017
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.
Copyright © 2017 Wolters Kluwer Health, Inc.
All rights reserved.
DOI:10.1097/NHH.0000000000000495
REFERENCES
American Diabetes Association. (2016).
Hypoglycemia. Retrieved from http://
www.diabetes.org/living-with-diabetes/treatment-and-care/blood-glucosecontrol/hypoglycemia-low-blood.html
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
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.
Eli Lilly and Company. (2015). Lilly acquires phase III intranasal glucagon
from Locemia Solutions. Retrieved from
https://investor.lilly.com/releasedetail.
cfm?ReleaseID=936055
Locemia Solutions. (2016). Developing a solution: Phase 3 trials are underway. Retrieved
from http://www.locemia.com/whats-new
Rickels, M. R., Ruedy, K. J., Foster, N. C.,
Piché, 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
Sherr, J. L., Ruedy, K. J., Foster, N. C., Piché,
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
Tucker, M. E. (2015). Intranasal glucagon
combats hypoglycemia in type I diabetes.
Retrieved from http://www.medscape.
com/viewarticle/856575
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 http://
www.easdvirtualmeeting.org/users/740
Home Healthcare Now
Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.
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