Duration of Action of Isophane (NPH) Insulin
NPH insulin (Humulin N) has a duration of action of approximately 12-18 hours, with onset at 2-4 hours and peak action at 4-6 hours after subcutaneous injection. 1
Pharmacokinetic Profile
NPH insulin demonstrates an intermediate-acting profile that differs substantially from both rapid-acting and long-acting insulin formulations:
- Onset of action: 2-4 hours after subcutaneous injection 2
- Peak effect: 4-6 hours after administration 1, 3
- Duration: The insulin effect persists for the full duration needed to provide basal coverage, though the exact endpoint varies by individual 3
Research comparing NPH to zinc insulins demonstrates that NPH formulations show a faster action profile, with plasma insulin levels reaching a plateau after approximately 3 hours, whereas zinc insulins only gradually increase over 5-6 hours 3. This makes NPH particularly well-suited for matching the hyperglycemic effects of intermediate-acting glucocorticoids like prednisone 1.
Clinical Implications for Timing
The pharmacokinetic profile of NPH makes it ideal for morning administration when managing steroid-induced hyperglycemia:
- When given in the morning, NPH peaks around 4-6 PM, aligning with the peak hyperglycemic effect of morning glucocorticoid doses 1
- This timing relationship is why NPH is specifically recommended to be administered concomitantly with intermediate-acting steroids 1
Important Caveats
NPH is not a truly "peakless" basal insulin, which creates specific clinical considerations:
- The pronounced peak action increases the risk of hypoglycemia during the 4-6 hour window after injection, particularly after nighttime dosing 2
- The presence of a peak and tail means NPH cannot maintain a constant basal level, potentially leading to premeal and fasting hyperglycemia 2
- For patients requiring true basal coverage without peaks, long-acting analogues like insulin glargine or detemir are more appropriate alternatives 1, 2
Mixing Considerations
When NPH is mixed with rapid-acting insulin, there is only a slight decrease in absorption rate without affecting total bioavailability:
- Clinical trials show that postprandial blood glucose response remains similar when rapid-acting insulin is mixed with NPH 4
- NPH and short-acting insulin formulations can be mixed and used immediately or stored for future use 4
- The mixture should be injected within 15 minutes before a meal when combining rapid-acting insulin with NPH 4