Glucagon for Neonatal Hypoglycaemia: Systematic Review and Meta-Analysis
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Updated: Oct 1, 2025
Biochemical Measurement of Neonatal Hypoxia
Published on: August 24, 2011
Eamon P G Walsh1, Jane M Alsweiler2, Julena Ardern3
1Liggins Institute, University of Auckland, Auckland, New Zealand.
Insights
Glucagon may raise blood glucose in newborns with hypoglycemia but doesn't prevent recurrence. More research is needed to confirm glucagon's effectiveness and safety for neonatal hypoglycemia treatment.
Area of Science:
- Neonatal Medicine
- Endocrinology
- Pharmacology
Background:
- Neonatal hypoglycemia is a common concern, with glucagon frequently used despite limited evidence on its efficacy and safety.
- Systematic assessment of glucagon's effects in treating neonatal hypoglycemia is lacking.
Approach:
- A systematic review was conducted, searching multiple databases (MEDLINE, CINAHL, EMBASE, CENTRAL) up to May 2021.
- Included studies compared glucagon to placebo or no treatment in infants, excluding those over one month old.
- Risk of bias, certainty of evidence, and meta-analysis were performed using established methodologies (ROB-2/ROBINS-I, GRADE, RevMan).
Key Points:
- Seven single-arm, non-randomized studies involving 348 infants were included; no randomized trials were found.
- Glucagon administration increased blood glucose by approximately 2.3 mmol/L within 1-2 hours (low certainty evidence).
- While normoglycemia was achieved in many infants, recurrent hypoglycemia was frequent (up to 55%).
Conclusions:
- There is a significant lack of high-quality evidence regarding glucagon's efficacy and safety for neonatal hypoglycemia.
- Current low-certainty evidence suggests a modest glucose-raising effect but highlights the common issue of recurrent hypoglycemia.
- High-quality randomized controlled trials are essential to establish the definitive role of glucagon in managing neonatal hypoglycemia.
Introduction:
Glucagon is often used in neonatal hypoglycaemia, but its effects have not been systematically assessed. We undertook a systematic review to determine the efficacy and safety of glucagon treatment for neonatal hypoglycaemia.
Methods:
We searched MEDLINE, CINAHL, EMBASE, and CENTRAL from inception until May 2021. We included studies that reported one or more prespecified outcomes and compared glucagon with placebo or no glucagon. Studies were excluded if the majority (>70%) of participants were >1 month of age. Two authors independently extracted data. We used ROB-2/modified ROBINS-I to assess risk of bias, GRADE for certainty of evidence, and RevMan for meta-analysis.
Results:
100 studies were screened, 37 reviewed in full, and seven single-arm non-randomised intervention studies, involving 348 infants, were included (no trials). Data were insufficient to undertake meta-analysis of the critical outcomes (time to blood glucose normalization, recurrent hypoglycaemia, neurocognitive impairment). In 3 studies, ≥80% of neonates achieved normoglycaemia within 4 h of glucagon administration. However, recurrent hypoglycaemia was common (up to 55%). Glucagon increased blood glucose concentration at 1-2 h by 2.3 mmol/L (95% CI 2.1, 2.5) (low certainty evidence, 6 studies, N = 323). There were few data for other important clinical outcomes.
Conclusion:
There is a paucity of evidence about the efficacy and safety of glucagon for treatment of neonatal hypoglycaemia. Low certainty evidence suggests that glucagon may increase blood glucose by ∼2.3 mmol/L but recurrent hypoglycaemia appears common. High-quality, randomized controlled trials are required to determine the role of glucagon in managing neonatal hypoglycaemia.
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