What is the duration of action for NPH (Neutral Protamine Hagedorn) insulin?

Duration of Action of NPH Insulin

NPH insulin has a duration of action of approximately 12-16 hours, with peak effects occurring at 8-12 hours after injection. 1

Pharmacokinetic Profile of NPH Insulin

NPH (Neutral Protamine Hagedorn) insulin is an intermediate-acting insulin with the following characteristics:

• Onset of action: Begins to work within 1-2 hours after injection 2
• Peak effect: Occurs at approximately 8-12 hours after injection 1
• Duration of action: Typically lasts 12-16 hours, though studies have shown variability with ranges from 14-25 hours 2

This pharmacokinetic profile differs significantly from other insulin types:

• Short-acting (regular) insulin: Peaks at 2-3 hours, lasts 5-8 hours
• Long-acting insulins (e.g., glargine): Peakless profile lasting up to 24 hours 3

Clinical Implications of NPH Timing

The timing of NPH insulin administration is crucial due to its peak effect:

• Morning administration: When given in the morning, the peak effect occurs in the afternoon/evening, which may help cover daytime hyperglycemia but could be insufficient for overnight control 4
• Bedtime administration: When given at bedtime, the peak occurs overnight, which can better control fasting hyperglycemia but increases risk of nocturnal hypoglycemia 4, 5

Hypoglycemia Risk

The pronounced peak of NPH insulin at 8-12 hours creates a higher risk of hypoglycemia compared to newer long-acting insulin analogs. Studies have shown that patients using NPH insulin experience more nocturnal hypoglycemia (24% vs. 9.9%) compared to those using insulin glargine 5.

Mixing NPH with Other Insulins

When using NPH in combination with other insulins, important considerations include:

• NPH can be mixed with rapid-acting or short-acting insulins 6
• When mixed with rapid-acting insulin, the mixture should be injected within 15 minutes before a meal 6
• The pharmacokinetic profile of rapid-acting insulin is slightly affected when mixed with NPH, with a small decrease in absorption rate but not total bioavailability 6
• NPH should not be mixed with phosphate-buffered insulins or lente insulins due to potential precipitation and unpredictable action 6

Practical Dosing Considerations

For patients requiring NPH insulin:

• Initial dosing typically ranges from 0.1-0.2 units/kg/day 1
• Dose adjustments should be made in increments of 10-20% every 1-2 days based on blood glucose patterns 1
• When used for steroid-induced hyperglycemia, a ratio of approximately 0.4-0.5 units of NPH per mg of prednisone may be considered 1
• When tapering steroids, insulin must be reduced proportionally to prevent hypoglycemia 1

Common Pitfalls and Caveats

1. Overbasalization: Using excessive doses of NPH (>0.5 IU/kg) may lead to overbasalization, causing high bedtime-morning glucose differentials and increased hypoglycemia risk 6

2. Storage and Handling: NPH insulin should appear uniformly cloudy; any clumping, frosting, precipitation, or change in clarity may indicate loss of potency 1

3. Variability: NPH insulin has greater inter-individual variability in absorption and action compared to newer insulin analogs like glargine 3

4. Nocturnal Hypoglycemia: The peak action of NPH at 8-12 hours after injection makes nocturnal hypoglycemia a significant risk when administered at bedtime 5

NPH insulin remains a useful option for many patients, particularly when cost is a consideration, but its pronounced peak and shorter duration compared to newer analogs necessitates careful timing of administration and vigilant glucose monitoring.