Duration of Action of NPH Insulin
NPH (Neutral Protamine Hagedorn) insulin has an onset of action at 2-4 hours, peaks at 4-6 hours, and has a total duration of action of approximately 13 hours. 1, 2
Pharmacokinetic Profile of NPH Insulin
NPH insulin demonstrates the following time-action characteristics:
- Onset of action: 2-4 hours (typically around 3 hours) 1
- Peak effect: 4-6 hours after administration 3, 1
- Duration of action: 10-13 hours 1, 2
This intermediate-acting insulin profile contrasts with other insulin types:
- Rapid-acting insulins: peak at 1-2 hours with 3-4 hour duration 3
- Regular insulin: peak at 3-4 hours with 6-8 hour duration 3
Clinical Implications of NPH Duration
Timing of Administration
The pharmacokinetic profile of NPH makes it particularly useful in specific clinical scenarios:
- When administered with glucocorticoids, NPH's peak action (4-6 hours) aligns well with the peak hyperglycemic effect of steroids 3
- For patients on once or twice-daily steroids, NPH is typically administered in addition to daily basal-bolus insulin or oral antidiabetic medications 3
Dosing Considerations
- When used for steroid-induced hyperglycemia, a common approach is dividing the daily dose as 2/3 in the morning and 1/3 in the evening 3
- For nocturnal tube feeding, NPH administered at the initiation of feeding represents a reasonable approach 3
Important Caveats and Considerations
Variability in Action
While the average duration is approximately 13 hours, studies have shown considerable variability between patients:
- Some research has reported durations ranging from 10-15 hours 4
- Older studies have even suggested longer durations of up to 25 hours in some individuals 5
Mixing with Other Insulins
When mixing NPH with other insulins, follow these guidelines:
- NPH can be mixed with rapid-acting insulin 6
- When mixed with rapid-acting insulin, the mixture should be injected within 15 minutes before a meal 6
- NPH should not be mixed with lente insulins due to potential precipitation of zinc phosphate 6
- Currently available NPH and short-acting insulin formulations when mixed may be used immediately or stored for future use 6
Safety Considerations
- In elderly patients, NPH has been associated with higher rates of hypoglycemia compared to basal-bolus regimens with insulin analogs 3
- The peak effect of NPH at 4-6 hours can increase the risk of hypoglycemia during this time window, particularly if not aligned with meal timing or physical activity
Modern Alternatives to NPH
Long-acting insulin analogs like insulin glargine offer advantages over NPH:
- Longer duration of action (up to 24 hours)
- Smoother time-action profile with less pronounced peaks
- Lower risk of nocturnal hypoglycemia 2, 4
These characteristics make long-acting analogs potentially more suitable for basal insulin replacement in many patients, especially those with type 1 diabetes 4.