NPH Insulin

NPH (Neutral Protamine Hagedorn) insulin is an intermediate-acting insulin used for basal glucose control.

It has a pronounced peak and shorter duration compared to long-acting insulin analogs.

→ Insulin Therapy

NPH insulin binds to the insulin receptor (tyrosine kinase receptor).

This activates:

• IRS signaling pathways
• PI3K/Akt cascade
• GLUT4 translocation in muscle and adipose tissue

Primary effect:

• Suppression of hepatic glucose production
• Basal glucose control

NPH insulin is human insulin complexed with:

• Protamine

Protamine slows insulin absorption after subcutaneous injection.

After injection:

• Protamine must be enzymatically degraded
• Insulin is gradually released

This produces:

• Delayed onset
• Clear peak
• Intermediate duration

Onset:

• 1–2 hours

Peak:

• 4–8 hours (pronounced peak)

Duration:

• 12–18 hours

Compared to:

• Glargine → shorter duration, clear peak
• Detemir → more variability
• Degludec → much shorter duration

Often requires twice-daily dosing.

• Basal insulin (older regimens)
• Sometimes combined in premixed formulations
• Cost-effective option

Historically widely used before modern basal analogs.

• Pronounced peak increases hypoglycemia risk
• Higher nocturnal hypoglycemia risk
• Greater day-to-day variability
• Often requires twice-daily dosing

• Hypoglycemia (especially nocturnal)
• Weight gain
• Injection site reactions

Risk increased with:

• Irregular meals
• Missed food intake
• Excess dosing

Glargine:

• No pronounced peak
• Lower nocturnal hypoglycemia

Detemir:

• More stable pharmacokinetics

Degludec:

• Ultra-long duration
• Most stable profile

NPH:

• Has peak
• Higher variability
• Less expensive

• Intermediate-acting insulin
• Complexed with protamine
• Clear peak at 4–8 hours
• Higher hypoglycemia risk than analogs
• Often requires twice-daily dosing
• Lower cost option

• Insulin Therapy
• Glargine
• Detemir
• Degludec
• Diabetes Pharmacology