Duration of Action of Actrapid (Human Regular Insulin)
Actrapid (human regular insulin) has a duration of action of approximately 16 hours in insulin-treated diabetic patients, which is substantially longer than the 6-8 hours commonly cited in older references.
Pharmacokinetic Profile Based on Clinical Evidence
The most rigorous clinical study measuring Actrapid's actual duration of action demonstrated:
- Onset of action: 1.2 hours (range 0.5-2 hours) 1
- Peak effect: 5.7 hours (range 4-8 hours) after subcutaneous injection 1
- Total duration of action: 16.2 hours (range 9-24 hours) 1
- Free insulin levels: Peak at 2.7 hours and return to baseline by 8.8 hours 1
This prolonged duration of 16+ hours is considerably longer than traditional textbook values and has critical implications for dosing schedules and hypoglycemia risk 1.
Clinical Context and Comparison with Insulin Analogs
The 2024 American Diabetes Association guidelines emphasize that rapid-acting analogs have a quicker onset and peak and shorter duration of action than regular human insulin 2. This distinction is clinically important:
- Rapid-acting analogs (like Humalog): 3-4 hour duration 3
- Regular human insulin (Actrapid): 16+ hour duration 1
- NPH insulin: 25 hour duration with peak at 11 hours 1
Critical Clinical Implications
Hypoglycemia Risk
The prolonged 16-hour action profile of Actrapid creates significant overlap between doses when used in multiple daily injection regimens, substantially increasing hypoglycemia risk compared to rapid-acting analogs 2, 4. This is particularly concerning for:
Timing Requirements
Actrapid requires injection 30 minutes before meals for optimal postprandial glucose control, whereas rapid-acting analogs can be given immediately pre-meal 5, 6. When Actrapid is injected immediately before eating (rather than 30 minutes prior), postprandial glucose control is significantly worse 5.
Dosing Flexibility
The extended duration means Actrapid provides some basal insulin coverage beyond its intended prandial effect, which can complicate insulin regimen design and increase the risk of delayed hypoglycemia hours after meals 1.
Common Pitfalls to Avoid
- Do not assume 6-8 hour duration: This outdated estimate underestimates actual duration by more than 50%, leading to dose stacking and hypoglycemia 1
- Do not inject immediately before meals: Allow 30 minutes for optimal postprandial control 5, 6
- Do not overlook prolonged tail effect: The insulin activity persists well beyond the peak, requiring careful consideration of meal timing and snacks 1
Current Guideline Perspective
While the American Diabetes Association acknowledges that regular human insulin was successfully used in landmark trials like the DCCT 2, current guidelines favor analog insulins due to less hypoglycemia, less weight gain, and lower A1C in type 1 diabetes 2, 7. However, in resource-limited settings where cost is prohibitive, human insulin remains appropriate with careful patient education about timing and hypoglycemia risk 4, 7.