When does NPH (Neutral Protamine Hagedorn) insulin peak?

NPH Insulin Peak Action Time

NPH insulin peaks at approximately 4-6 hours after administration, making it particularly suitable for managing steroid-induced hyperglycemia when timed to coincide with the peak hyperglycemic effect of glucocorticoids. 1, 2

Pharmacokinetic Profile of NPH Insulin

• NPH (Neutral Protamine Hagedorn) insulin is an intermediate-acting insulin with onset, peak, and duration characteristics that differ significantly from other insulin formulations 1
• The peak action of NPH insulin occurs approximately 4-6 hours after subcutaneous injection 2, 3
• The total duration of action for NPH insulin is approximately 10-15 hours, though some studies have reported it lasting up to 13-25 hours 4, 5
• Unlike long-acting insulin analogs such as insulin glargine which have a relatively peakless action profile, NPH has a distinct peak that must be considered when planning insulin regimens 4, 6

Clinical Applications Based on NPH Peak Timing

• The American Diabetes Association recommends NPH insulin specifically for steroid-induced hyperglycemia because its peak action at 4-6 hours aligns with the peak hyperglycemic effect of morning-administered glucocorticoids 1, 2
• For patients on once or twice-daily steroids, NPH insulin is the standard approach and should be administered concomitantly with intermediate-acting steroids to match their pharmacokinetic profiles 1
• When using NPH for enteral nutrition coverage in hospitalized patients, the timing of administration should consider the 4-6 hour peak to coincide with nutritional load 1

Practical Considerations for Dosing

• Due to NPH's peak action at 4-6 hours, there is an increased risk of hypoglycemia during this time period, especially in patients with poor oral intake 1
• When NPH is administered at bedtime, the peak action occurring 4-6 hours later (middle of the night) can lead to nocturnal hypoglycemia, a significant clinical concern 7
• For hospitalized patients receiving enteral nutrition, NPH can be administered every 8-12 hours (two or three times daily) to provide more consistent coverage throughout the day 1

Comparison with Other Insulin Formulations

• Regular insulin peaks earlier than NPH, with studies showing peak action at approximately 2-5.7 hours after injection 5, 8
• Long-acting insulin analogs like insulin glargine have a relatively peakless action profile lasting approximately 24 hours, making them more suitable for basal insulin coverage 4, 6
• The distinct 4-6 hour peak of NPH makes it less ideal as a basal insulin compared to newer long-acting analogs, but more appropriate for specific clinical scenarios like steroid coverage 7

Important Considerations and Pitfalls

• The peak action of NPH at 4-6 hours must be considered when planning meal timing and dosing schedules to avoid hypoglycemia 1
• When using NPH for steroid coverage, it's essential to adjust the dose when steroids are tapered to prevent hypoglycemia 3
• For patients requiring both basal and prandial coverage, NPH alone may be insufficient due to its peak action profile, and additional rapid-acting insulin may be needed 4
• In older studies, NPH was found to have a peak effect at 4-19 hours (mean 11 hours), highlighting the potential variability in individual responses 5