What are the administration directions for short acting insulin (e.g. insulin lispro (Humalog), insulin aspart (NovoLog), insulin glulisine (Apidra))?

Short-Acting Insulin Administration Directions

Short-acting insulin analogs (lispro, aspart, glulisine) should be injected subcutaneously within 15 minutes before a meal or within 20 minutes after starting a meal, administered into the abdomen, thigh, or upper arm. 1

Timing of Administration

• Inject 0-15 minutes before meals for optimal postprandial glucose control 1, 2
• The FDA-approved label for insulin glulisine (Apidra) specifically states injection within 15 minutes before a meal OR within 20 minutes after starting a meal 1
• In hyperglycemic patients (glucose >10 mmol/L), injecting 15 minutes before meals significantly improves postprandial glucose excursion compared to injection at mealtime 3
• Avoid injecting 30 minutes before meals in routine practice, as this increases risk of late postprandial hypoglycemia despite better initial glucose control 3

Injection Sites and Technique

• Rotate injection sites within the same anatomical region (abdomen, thigh, or upper arm) rather than rotating between different regions 4, 1
• The abdomen provides the fastest absorption rate, followed by arms, thighs, and buttocks 4
• Do not inject into areas of lipodystrophy or localized cutaneous amyloidosis, as this distorts insulin absorption 1, 2
• Inspect the vial or pen before each use—rapid-acting insulins should appear clear and colorless 4

Combination with Other Insulins

• Short-acting insulin analogs should generally be used in regimens with intermediate or long-acting basal insulin 1
• When mixing with NPH insulin, draw the rapid-acting insulin into the syringe first and inject immediately after mixing 1
• Do not mix insulin glulisine with insulins other than NPH for subcutaneous injection 1
• When rapid-acting insulin is mixed with intermediate or long-acting insulin, inject within 15 minutes before a meal 4

Continuous Subcutaneous Infusion (Insulin Pump)

• Change insulin in the reservoir at least every 48 hours or according to pump manufacturer instructions, whichever is shorter 1
• Do not mix with other insulins or diluents when using an insulin pump 1
• Change infusion sets and insertion sites according to manufacturer guidelines 1
• Do not expose insulin in the pump reservoir to temperatures greater than 98.6°F (37°C) 1
• Rotate infusion sites within the same region to prevent lipodystrophy 1

Intravenous Administration

• Administer intravenously only under medical supervision with close monitoring of blood glucose and potassium levels 1
• Dilute to concentrations from 0.05 to 1 unit/mL in 0.9% sodium chloride using polyvinyl chloride (PVC) infusion bags 1
• Diluted insulin glulisine is stable at room temperature for 48 hours only in normal saline 1
• Not compatible with dextrose solution or Ringer's solution 1

Storage and Handling

• Insulin not in use should be refrigerated at 36-86°F (2-30°C) 4
• Insulin in use may be kept at room temperature to reduce local irritation from cold insulin 4
• Avoid extreme temperatures and excess agitation to prevent loss of potency 4
• Loss of potency may occur after a bottle has been in use for >1 month, especially if stored at room temperature 4

Critical Safety Considerations

• Always check insulin labels before administration to avoid medication errors between insulin products 1
• Increase frequency of blood glucose monitoring during changes to insulin regimen 1
• Dosage adjustments may be needed with changes in physical activity, meal patterns, renal/hepatic function, or during acute illness 1
• Patients using insulin pumps must be trained to administer insulin by injection and have alternate insulin therapy available in case of pump failure 1

Pharmacokinetic Profile

• Onset of action begins within 15 minutes of subcutaneous administration 5
• Peak insulin levels occur 30-90 minutes after administration 5
• Duration of activity is less than 5 hours 5
• These analogs provide faster absorption, earlier and greater insulin peak, and more rapid postpeak decrease compared to regular human insulin 6, 5