Can glucagon be safely reconstituted with normal saline instead of sterile water?

Glucagon Reconstitution with Normal Saline

Glucagon should not be reconstituted with normal saline instead of sterile water, as this practice is not recommended by current guidelines and may affect the stability and efficacy of the medication. 1

Proper Glucagon Administration

The American Diabetes Association's 2024-2025 Standards of Care in Diabetes provides clear guidance on glucagon administration:

• Glucagon is indicated for treatment of hypoglycemia in people unable or unwilling to consume carbohydrates by mouth 1
• Traditional glucagon formulations are dispensed as powder requiring reconstitution prior to injection 1
• Specific product instructions must be followed to ensure safe and effective use 1

Available Glucagon Formulations

Current guidelines recommend newer formulations that don't require reconstitution:

• Intranasal glucagon powder
• Ready-to-inject glucagon preparations (prefilled pens/syringes)
• Dasiglucagon (prefilled pens/syringes)

These newer formulations are preferred due to:

• Ease of administration
• More rapid correction of hypoglycemia
• Improved physical and chemical stability 1

Stability Concerns with Glucagon

Research indicates that glucagon has significant stability issues:

• Glucagon rapidly forms amyloid fibrils after reconstitution 2
• Aggregation can lead to insoluble gels 2
• Glucagon degrades over time through deamidation (conversion of asparagine to aspartic acid) 2
• pH significantly affects stability - fibrillation occurs rapidly at acidic pH 2

Using normal saline instead of the provided diluent could potentially alter these stability characteristics and affect efficacy.

Recommended Approach

1. Always use the diluent provided with the glucagon kit for reconstitution
2. Consider switching to newer formulations that don't require reconstitution:
   • Intranasal glucagon
   • Ready-to-use injectable formulations 3, 4

Important Clinical Considerations

• All individuals treated with insulin or at high risk of hypoglycemia should be prescribed glucagon 1
• Clinicians should routinely review patients' access to glucagon, as appropriate prescribing is very low in current practice 1
• Family members, caregivers, and others in close contact should be trained on glucagon administration 1, 5
• Expired glucagon products should be replaced to ensure efficacy 1

Avoiding Common Pitfalls

• Do not substitute diluents - Use only the provided diluent with traditional glucagon kits
• Consider accessibility issues - The complexity of mixing traditional glucagon may lead to errors during emergency situations 6
• Be aware of storage requirements - Follow specific product instructions for storage 1
• Recognize the underutilization problem - Traditional glucagon is underutilized due to administration challenges 3, 4

The availability of newer, ready-to-use glucagon formulations has significantly improved the management of severe hypoglycemia, making them the preferred option over traditional reconstituted formulations.