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

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