Intranasal Glucagon for Treatment of Insulin-

Induced Hypoglycemia in Adults With Type 1

Diabetes: A Randomized Crossover
Noninferiority Study

Michael R. Rickels, Katrina J. Ruedy, Nicole C. Foster, Claude A. Pich,

Hlne Dulude, Jennifer L. Sherr, William V. Tamborlane, Kathleen E.
Bethin, Linda A. DiMeglio, R. Paul Wadwa, Andrew J. Ahmann, Michael J.
Haller, Brandon M. Nathan, Santica M. Marcovina, Emmanouil
Rampakakis, Linyan Meng, and Roy W. Beck, for the T1D Exchange
Intranasal Glucagon Investigators

Diabetes Care
Volume 39: 264270
February 2016
 In the most severe hypoglycemic events, administration of oral
carbohydrate by a second party is precluded because the patient is
combative, unconscious, or having a seizure.

Severe hypoglycemia, can be associated with significant morbidity

and mortality

Glucagon, the principal counterregulatory hormone to insulin, is in-

hibited by insulin and fails to activate in response to hypoglycemia in
patients with type 1 diabetes

Available glucagon preparations are unstable in solution and available

only as a lyophilized powder that must be reconstituted in diluent
immediately prior to injection.
 STUDY OBJECTIVE

To compare the efficacy and safety of a needle-free

intranasal glucagon preparation with intramuscular glucagon
for treatment of insulin-induced hypoglycemia in adults with
type 1 diabetes.

Rickels M.R. et al. Diabetes Care 2016;39:264270

 STUDY DESIGN AND METHODS

Randomized crossover noninferiority trial was

conducted at eight clinical centers
Study included 75 adults with type 1 diabetes and
compared intranasal versus intramuscular glucagon for
treatment of hypoglycemia induced by intravenous
insulin
Success was dened as an increase in plasma glucose
to 70 or 20 mg/dL from the glucose nadir within 30
min after receiving glucagon

Rickels M.R. et al. Diabetes Care 2016;39:264270

 RESULTS

Mean plasma glucose at time of glucagon administration

was 48 8 and 49 8 mg/dL at the intranasal and
intramuscular visits, respectively
Success criteria were met at all but one intranasal visit and
at all intramuscular visits
Mean time to success was 16 min for intranasal and 13 min
for intramuscular
Head/facial discomfort was reported during 25% of
intranasal and 9% of intramuscular dosing visits; nausea
occurred with 35% and 38% of visits, respectively

Rickels M.R. et al. Diabetes Care 2016;39:264270

Rickels M.R. et al. Diabetes Care 2016;39:264270
Rickels M.R. et al. Diabetes Care 2016;39:264270
Rickels M.R. et al. Diabetes Care 2016;39:264270
Rickels M.R. et al. Diabetes Care 2016;39:264270
 CONCLUSIONS

Intranasal glucagon was highly effective in treating insulin-

induced hypoglycemia in adults with type 1 diabetes

Rickels M.R. et al. Diabetes Care 2016;39:264270