Glucagon for hypoglycemic episodes in insulin-treated diabetic patients: a systematic review and meta-analysis with a comparison of glucagon with dextrose and of different glucagon formulations

Glucagon is used as an emergency drug in hypoglycemia, mainly when the patient is unconscious. A few studies report on ineffectiveness of glucagon in relieving hypoglycemia. The present systematic review and meta-analysis evaluate the effectiveness of glucagon alone and in comparison with dextrose and the effectiveness of intranasal glucagon in comparison with injected glucagon. Studies were grouped into three groups: (1) reports on glucagon ineffectiveness; (2) comparison of glucagon and dextrose; (3) comparison of intranasal glucagon and injected glucagon. In groups 2 and 3, only controlled studies were included in the analysis, whether randomized or non-randomized studies. Appropriate methodology (PRISMA statement) was adhered to, and publication bias was formally assessed. Sixteen studies, published in any language as full papers, were analysed to identify predictors of ineffectiveness, and they were included in a meta-analysis (random effects model) to study the effect of different strategies. Intervention effect (number of failures) was expressed as odds ratio (OR), with 95 % confidence intervals. Failure rate ranged from 0.0 to 2.31 %, to 7.6 %, to 14.4 %, and to 59 %. Comparing glucagon and dextrose, the OR was 0.53 (0.20–1.42); comparing intranasal and intramuscular glucagon, the OR was 1.40 (0.18–10.93). Heterogeneity was low and not statistically significant. Publication bias was absent. These data indicate that ineffectiveness of glucagon is unfrequent, not different from dextrose; in addition, intranasal and injected glucagon are similarly effective. In the case of failure, a second dose can be administered.