Onset of Action for NPH Insulin
NPH insulin has an onset of action of approximately 1 hour after subcutaneous injection. 1
Pharmacokinetic Profile of NPH Insulin
NPH (Neutral Protamine Hagedorn) insulin is an intermediate-acting insulin with the following time-action profile:
This profile positions NPH insulin between rapid/short-acting insulins and long-acting insulin analogs in terms of onset and duration.
Clinical Implications of NPH's Onset
The 1-hour onset of NPH insulin has important clinical implications:
- Meal timing: When using NPH for prandial coverage, meals should be timed appropriately relative to injection to avoid early hypoglycemia
- Bedtime administration: When administered at bedtime, the 1-hour onset means it begins working during the night, which can help control fasting hyperglycemia but also increases risk of nocturnal hypoglycemia 3
Comparison with Other Insulin Types
| Insulin Type | Onset | Peak (hours) | Duration (hours) |
|---|---|---|---|
| Rapid-acting (aspart, lispro) | 5 minutes | 1-2 | 3-4 |
| Regular insulin | 15 minutes | 3-4 | 6-8 |
| NPH | 1 hour | 6-8 | 12 |
| Glargine | 1 hour | None | 24 |
Clinical Applications
Basal-Bolus Regimens
When using NPH as part of a basal-bolus regimen, its 1-hour onset and pronounced peak at 6-8 hours must be considered. Unlike peakless long-acting analogs like glargine, NPH's peak action can cause hypoglycemia if not matched with food intake 1.
Split Evening Dosing
Due to NPH's onset and peak characteristics, splitting the evening insulin regimen (regular insulin at dinner and NPH at bedtime) rather than mixing them before dinner has been shown to:
- Reduce nocturnal hypoglycemia
- Improve glycemic control
- Lower HbA1c values 3
Special Situations
Enteral/Parenteral Feeding
NPH insulin can be administered every 8-12 hours to cover nutritional requirements in patients receiving enteral or parenteral nutrition 1. This dosing schedule aligns with NPH's pharmacokinetic profile.
Glucocorticoid Therapy
NPH insulin is particularly useful for counteracting steroid-induced hyperglycemia because its peak action (4-6 hours) coincides with the peak plasma levels of intermediate-acting glucocorticoids like prednisone 1. For patients on once or twice-daily steroids, NPH is recommended to be administered concomitantly with the steroid dose 1.
Practical Considerations
- NPH insulin appears uniformly cloudy when properly mixed 1
- Requires resuspension before administration by gently rolling the vial
- Can be mixed with rapid-acting or short-acting insulin in the same syringe for immediate use 1
- Should not be mixed with phosphate-buffered insulins or lente insulins due to potential precipitation 1
Understanding the 1-hour onset of NPH insulin is crucial for proper timing of injections and meal planning to optimize glycemic control while minimizing the risk of hypoglycemia.