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Intranasal Glucagon for Treatment of Insulin-Induced Hypoglycemia in Adults With Type 1 Diabetes: A Randomized Crossover Noninferiority Study
OBJECTIVE: Treatment of severe hypoglycemia with loss of consciousness or seizure outside of the hospital setting is presently limited to intramuscular glucagon requiring reconstitution immediately prior to injection, a process prone to error or omission. A needle-free intranasal glucagon preparatio...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Diabetes Association
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4722945/ https://www.ncbi.nlm.nih.gov/pubmed/26681725 http://dx.doi.org/10.2337/dc15-1498 |
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author | Rickels, Michael R. Ruedy, Katrina J. Foster, Nicole C. Piché, Claude A. Dulude, Hélène Sherr, Jennifer L. Tamborlane, William V. Bethin, Kathleen E. DiMeglio, Linda A. Wadwa, R. Paul Ahmann, Andrew J. Haller, Michael J. Nathan, Brandon M. Marcovina, Santica M. Rampakakis, Emmanouil Meng, Linyan Beck, Roy W. |
author_facet | Rickels, Michael R. Ruedy, Katrina J. Foster, Nicole C. Piché, Claude A. Dulude, Hélène Sherr, Jennifer L. Tamborlane, William V. Bethin, Kathleen E. DiMeglio, Linda A. Wadwa, R. Paul Ahmann, Andrew J. Haller, Michael J. Nathan, Brandon M. Marcovina, Santica M. Rampakakis, Emmanouil Meng, Linyan Beck, Roy W. |
author_sort | Rickels, Michael R. |
collection | PubMed |
description | OBJECTIVE: Treatment of severe hypoglycemia with loss of consciousness or seizure outside of the hospital setting is presently limited to intramuscular glucagon requiring reconstitution immediately prior to injection, a process prone to error or omission. A needle-free intranasal glucagon preparation was compared with intramuscular glucagon for treatment of insulin-induced hypoglycemia. RESEARCH DESIGN AND METHODS: At eight clinical centers, a randomized crossover noninferiority trial was conducted involving 75 adults with type 1 diabetes (mean age, 33 ± 12 years; median diabetes duration, 18 years) to compare intranasal (3 mg) versus intramuscular (1 mg) glucagon for treatment of hypoglycemia induced by intravenous insulin. Success was defined as an increase in plasma glucose to ≥70 mg/dL or ≥20 mg/dL from the glucose nadir within 30 min after receiving glucagon. 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 (98.7% vs. 100%; difference 1.3%, upper end of 1-sided 97.5% CI 4.0%). Mean time to success was 16 min for intranasal and 13 min for intramuscular (P < 0.001). Head/facial discomfort was reported during 25% of intranasal and 9% of intramuscular dosing visits; nausea (with or without vomiting) occurred with 35% and 38% of visits, respectively. CONCLUSIONS: Intranasal glucagon was highly effective in treating insulin-induced hypoglycemia in adults with type 1 diabetes. Although the trial was conducted in a controlled setting, the results are applicable to real-world management of severe hypoglycemia, which occurs owing to excessive therapeutic insulin relative to the impaired or absent endogenous glucagon response. |
format | Online Article Text |
id | pubmed-4722945 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | American Diabetes Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-47229452017-02-01 Intranasal Glucagon for Treatment of Insulin-Induced Hypoglycemia in Adults With Type 1 Diabetes: A Randomized Crossover Noninferiority Study Rickels, Michael R. Ruedy, Katrina J. Foster, Nicole C. Piché, Claude A. Dulude, Hélène Sherr, Jennifer L. Tamborlane, William V. Bethin, Kathleen E. DiMeglio, Linda A. Wadwa, R. Paul Ahmann, Andrew J. Haller, Michael J. Nathan, Brandon M. Marcovina, Santica M. Rampakakis, Emmanouil Meng, Linyan Beck, Roy W. Diabetes Care Epidemiology/Health Services Research OBJECTIVE: Treatment of severe hypoglycemia with loss of consciousness or seizure outside of the hospital setting is presently limited to intramuscular glucagon requiring reconstitution immediately prior to injection, a process prone to error or omission. A needle-free intranasal glucagon preparation was compared with intramuscular glucagon for treatment of insulin-induced hypoglycemia. RESEARCH DESIGN AND METHODS: At eight clinical centers, a randomized crossover noninferiority trial was conducted involving 75 adults with type 1 diabetes (mean age, 33 ± 12 years; median diabetes duration, 18 years) to compare intranasal (3 mg) versus intramuscular (1 mg) glucagon for treatment of hypoglycemia induced by intravenous insulin. Success was defined as an increase in plasma glucose to ≥70 mg/dL or ≥20 mg/dL from the glucose nadir within 30 min after receiving glucagon. 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 (98.7% vs. 100%; difference 1.3%, upper end of 1-sided 97.5% CI 4.0%). Mean time to success was 16 min for intranasal and 13 min for intramuscular (P < 0.001). Head/facial discomfort was reported during 25% of intranasal and 9% of intramuscular dosing visits; nausea (with or without vomiting) occurred with 35% and 38% of visits, respectively. CONCLUSIONS: Intranasal glucagon was highly effective in treating insulin-induced hypoglycemia in adults with type 1 diabetes. Although the trial was conducted in a controlled setting, the results are applicable to real-world management of severe hypoglycemia, which occurs owing to excessive therapeutic insulin relative to the impaired or absent endogenous glucagon response. American Diabetes Association 2016-02 2015-12-17 /pmc/articles/PMC4722945/ /pubmed/26681725 http://dx.doi.org/10.2337/dc15-1498 Text en © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. |
spellingShingle | Epidemiology/Health Services Research Rickels, Michael R. Ruedy, Katrina J. Foster, Nicole C. Piché, Claude A. Dulude, Hélène Sherr, Jennifer L. Tamborlane, William V. Bethin, Kathleen E. DiMeglio, Linda A. Wadwa, R. Paul Ahmann, Andrew J. Haller, Michael J. Nathan, Brandon M. Marcovina, Santica M. Rampakakis, Emmanouil Meng, Linyan Beck, Roy W. Intranasal Glucagon for Treatment of Insulin-Induced Hypoglycemia in Adults With Type 1 Diabetes: A Randomized Crossover Noninferiority Study |
title | Intranasal Glucagon for Treatment of Insulin-Induced Hypoglycemia in Adults With Type 1 Diabetes: A Randomized Crossover Noninferiority Study |
title_full | Intranasal Glucagon for Treatment of Insulin-Induced Hypoglycemia in Adults With Type 1 Diabetes: A Randomized Crossover Noninferiority Study |
title_fullStr | Intranasal Glucagon for Treatment of Insulin-Induced Hypoglycemia in Adults With Type 1 Diabetes: A Randomized Crossover Noninferiority Study |
title_full_unstemmed | Intranasal Glucagon for Treatment of Insulin-Induced Hypoglycemia in Adults With Type 1 Diabetes: A Randomized Crossover Noninferiority Study |
title_short | Intranasal Glucagon for Treatment of Insulin-Induced Hypoglycemia in Adults With Type 1 Diabetes: A Randomized Crossover Noninferiority Study |
title_sort | intranasal glucagon for treatment of insulin-induced hypoglycemia in adults with type 1 diabetes: a randomized crossover noninferiority study |
topic | Epidemiology/Health Services Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4722945/ https://www.ncbi.nlm.nih.gov/pubmed/26681725 http://dx.doi.org/10.2337/dc15-1498 |
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