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Acta Diabetol. 2020 Feb 6. doi: 10.1007/s00592-020-01483-y. [Epub ahead of print]

Intranasal versus injectable glucagon for hypoglycemia in type 1 diabetes: systematic review and meta-analysis.

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Dipartimento di Scienze della Salute, Università degli Studi di Milano, Ospedale San Paolo, Via Antonio di Rudinì 8, 20142, Milan, Italy.
IRCCS MultiMedica, Milan, Italy.



Glucagon is used to resolve severe hypoglycemia in unconscious patients with diabetes, requiring third-party assistance. A few studies have shown that intranasal (IN) glucagon causes resolution of hypoglycemia in insulin-treated patients with type 1 (T1DM) diabetes. This systematic review and meta-analysis updates the comparison of the effectiveness of IN glucagon with injected intramuscular/subcutaneous (IM/SC) glucagon in treatment of hypoglycemia in T1DM.


Controlled randomized studies were considered; eight studies, published in English, were included in a meta-analysis (random-effects model). Intervention effect (resolution of hypoglycemia) was expressed as odds ratio (OR), with 95% confidence intervals. Meta-regression was employed to correlate the effect with size of studies, age of patients, basal blood glucose levels.


In a total of 467 treatments in 269 patients with IN and IM/SC glucagon, the OR IN versus IM/SC was 0.61 (CI 0.13-2.82); since four of eight studies showed 100% effectiveness, a simulation was made with 1 failure for each treatment; in this simulation analysis, the OR was 0.80 (95% CI 0.28-2.32). Heterogeneity was low and not statistically significant. Publication bias was absent, and quality of papers was high. At meta-regression, no correlation was found between the effect and number of patients in each study, age of patients, basal blood glucose levels. No study formally compared IN versus IM/SC in unconscious patients.


This meta-analysis indicates that in conscious T1DM patients IN glucagon and IM/SC glucagon are equally effective in resolution of hypoglycemia.


Glucagon; Hypoglycemia; Insulin; Meta-analysis; Nasal glucagon; Type 1 diabetes


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