What types of insulin are in NPH (Neutral Protamine Hagedorn) insulin?

Types of Insulin in NPH (Neutral Protamine Hagedorn) Insulin

NPH insulin is an intermediate-acting human insulin formulation that contains recombinant DNA-derived human insulin combined with protamine to delay its absorption and extend its duration of action. 1

Composition of NPH Insulin

• NPH insulin is made of human insulin that has been modified with protamine (a protein) and zinc to create an intermediate-acting insulin formulation 1
• It is recombinant DNA-derived human insulin, not an insulin analog (which would have a modified amino acid sequence) 1
• The "NPH" abbreviation stands for Neutral Protamine Hagedorn, named after its neutral pH and the protamine component that gives it its intermediate-acting profile 2

Pharmacokinetic Properties of NPH Insulin

• NPH insulin has an onset of action of approximately 2-4 hours after injection 2
• It has a peak action period (unlike true basal insulins which are designed to be peakless) 2
• The duration of action is intermediate, typically lasting 12-18 hours, which often necessitates twice-daily dosing for optimal coverage 1
• NPH insulin has higher day-to-day variability in glucose-lowering effect compared to long-acting insulin analogs 3, 4

Clinical Considerations

• NPH insulin can be used as basal insulin therapy in both type 1 and type 2 diabetes, though it is not a true "peakless" basal insulin 1
• It can be administered once or twice daily, though twice-daily administration is often required for optimal glycemic control 1, 5
• NPH insulin can be mixed with short-acting (regular) or rapid-acting insulin analogs in the same syringe to provide both basal and prandial coverage 1
• Pre-mixed formulations containing NPH insulin are available (e.g., 70% NPH/30% regular, 50% NPH/50% regular) 1

Comparison to Other Insulin Types

• Unlike long-acting insulin analogs (glargine, detemir, degludec), NPH insulin has a pronounced peak effect that can increase the risk of hypoglycemia, particularly overnight 1, 3
• NPH insulin has a higher risk of hypoglycemia compared to long-acting insulin analogs, though in real-world settings this difference may be less pronounced when patients are treated to conventional targets 1
• NPH insulin is significantly less expensive than long-acting insulin analogs, making it an important option in resource-limited settings 1

Clinical Implications

• The peak action of NPH insulin can lead to an increased risk of hypoglycemia, particularly nocturnal hypoglycemia when administered at bedtime 3, 4
• Due to its pharmacokinetic profile, NPH insulin cannot maintain a constant basal insulin level throughout the day, which can lead to premeal and fasting hyperglycemia 2
• When switching between NPH insulin and other insulin formulations, dose adjustments and close monitoring are required 1

Human insulin in NPH formulations has demonstrated reduction in microvascular complications and, with long-term follow-up, all-cause mortality and diabetes-related death 1.