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

Acta Diabetol. 2020 Jun;57(6):743-749. doi: 10.1007/s00592-020-01483-y. Epub 2020 Feb 6.

Abstract

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.

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

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Administration, Intranasal
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 1 / blood*
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Diabetes Mellitus, Type 1 / epidemiology
  • Glucagon / administration & dosage*
  • Glucagon / adverse effects
  • Humans
  • Hypoglycemia / chemically induced
  • Hypoglycemia / drug therapy*
  • Hypoglycemia / epidemiology
  • Injections, Intramuscular
  • Injections, Subcutaneous
  • Insulin / administration & dosage
  • Insulin / adverse effects*
  • Randomized Controlled Trials as Topic / statistics & numerical data
  • Treatment Outcome

Substances

  • Blood Glucose
  • Insulin
  • Glucagon