Humulin N is human NPH (Neutral Protamine Hagedorn) insulin — an intermediate-acting insulin used for basal (background) blood sugar coverage. It has onset in 1 to 3 hours, a peak at 4 to 12 hours, and duration of 12 to 18 hours. The cloudy suspension must be gently rolled to resuspend before each injection. Humulin N is much cheaper than modern long-acting basal analogs and remains a guideline option for pregnancy, steroid-induced hyperglycemia, and cost-sensitive patients. Dose is individualized with a prescriber.
What Humulin N Is
Humulin N is the brand name for NPH (Neutral Protamine Hagedorn) human insulin, manufactured by Eli Lilly. It is one of the original intermediate-acting insulins, first introduced in 1946 by Danish researcher Hans Christian Hagedorn. NPH remained the standard basal insulin for decades before the introduction of long-acting analogs like glargine and detemir in the early 2000s.
Humulin N is supplied as 10 mL U-100 vials and 3 mL U-100 KwikPens. The equivalent product from Novo Nordisk is Novolin N. A Walmart-exclusive version of Novolin N is sold as ReliOn over the counter (without a prescription) for low cost.
How Humulin N Works
Humulin N is regular human insulin combined with protamine sulfate in a 1:1 ratio. Protamine is a small protein extracted historically from fish sperm (now made recombinantly) that binds to insulin and slows its absorption from the subcutaneous tissue. The result is intermediate-duration coverage — slower onset and longer duration than regular insulin, but shorter and less stable than modern basal analogs.
Once absorbed, NPH insulin acts identically to native human insulin — binding insulin receptors on liver, muscle, and fat tissue to lower blood glucose.
Pharmacokinetics: Onset, Peak, Duration
| Parameter | Humulin N (NPH) |
|---|---|
| Onset of action | 1 to 3 hours |
| Peak effect | 4 to 12 hours |
| Duration of action | 12 to 18 hours |
| Appearance | Cloudy suspension — requires resuspension |
| Concentration | U-100 (100 units/mL) |
| Typical dosing | Twice daily (most common) or once daily at bedtime |
Who Humulin N Is For
- Adults with type 1 or type 2 diabetes who need basal insulin coverage
- Children with type 1 or type 2 diabetes
- Pregnant patients needing basal insulin (NPH has extensive pregnancy data)
- People with steroid-induced hyperglycemia — NPH peak can be timed to match steroid dose peak
- Cost-sensitive patients who cannot afford modern basal analogs
- Patients without insurance or with limited prescription coverage
How Humulin N Is Used
- Resuspend by gently rolling the vial or pen between the palms 10 to 20 times until the solution is uniformly cloudy — do not shake
- Inject subcutaneously into the abdomen, thigh, upper arm, or buttock
- Twice-daily dosing typically uses about two-thirds of the total daily dose in the morning and one-third in the evening
- Once-daily dosing is usually at bedtime, with oral medications during the day
- Site rotation reduces lipohypertrophy
Starting dose, titration, and combinations with mealtime insulin are individualized by the prescriber based on diabetes type, weight, A1C, and glucose monitoring.
Humulin N vs Long-Acting Basal Analogs
| Insulin | Onset | Peak | Duration | Appearance | Approximate Monthly Cost |
|---|---|---|---|---|---|
| Humulin N (NPH) | 1 to 3 hr | 4 to 12 hr | 12 to 18 hr | Cloudy | $25 to $50 per vial |
| Lantus (glargine U-100) | 1 to 3 hr | Near-flat | ~24 hr | Clear | $200 to $400 |
| Basaglar (glargine biosimilar) | 1 to 3 hr | Near-flat | ~24 hr | Clear | $100 to $300 |
| Toujeo (glargine U-300) | 1 to 6 hr | Near-flat | ~36 hr | Clear | $300 to $400 |
| Tresiba (degludec) | 30 to 90 min | No peak | >42 hr | Clear | $300 to $500 |
| Levemir (detemir) | 1 to 2 hr | 4 to 9 hr | 12 to 24 hr | Clear | $300 to $400 |
Side Effects
- Hypoglycemia — most common side effect; nocturnal lows are more frequent than with long-acting basal analogs because of the 4 to 12 hour peak
- Weight gain — modest, typical of insulin therapy
- Injection site reactions — redness, itching, small lumps
- Lipodystrophy (lipohypertrophy or lipoatrophy) from repeated injections in the same spot
- Allergic reactions — local reactions to protamine are possible, though rare
- Hypokalemia (low potassium) — uncommon
- Peripheral edema, especially with thiazolidinediones
Specific Use Cases for NPH
Pregnancy
NPH has the longest safety record of any basal insulin in pregnancy. Many endocrinologists and maternal-fetal medicine specialists choose NPH or insulin detemir for pregnant patients needing basal insulin because human pregnancy data are extensive. Newer analogs (glargine and degludec) have less data, though emerging evidence supports their use.
Steroid-Induced Hyperglycemia
Patients taking morning prednisone or other corticosteroids often see a blood glucose peak 4 to 8 hours after the steroid dose. Morning NPH given with the steroid produces an insulin peak that aligns with the glucose peak, providing targeted coverage during the day with less overnight insulin effect.
Cost-Constrained Patients
For people without prescription drug coverage, NPH (especially Novolin N at Walmart for $25 per vial) is a critical option. ADA guidelines explicitly include NPH as an alternative basal insulin when cost is a barrier to long-acting analog use.
Storage and Handling
- Unopened vials and pens: refrigerate at 36 to 46 °F (2 to 8 °C)
- In use: room temperature up to 86 °F (30 °C) for up to 31 days (vials) or 14 days (KwikPens), then discard
- Do not freeze; do not expose to direct heat or sunlight
- Solution should be uniformly cloudy after rolling — discard if clumped, frosted, or has visible particles
- Do not share vials or pens between people
Practical Tips
- Roll the vial or pen between your palms 10 to 20 times before each use — do not shake
- Check that the suspension is uniformly cloudy and free of clumps
- Time bedtime doses about 1 hour after dinner to avoid stacking with mealtime insulin peaks
- Eat a small snack at bedtime if you are prone to nocturnal lows on twice-daily NPH
- Monitor for fasting hyperglycemia — if NPH duration runs short, fasting glucose may climb
Cost and Access
- Humulin N vial: about $25 to $50 retail without insurance
- Humulin N KwikPen: about $100 to $150 for a pack of five
- Novolin N at Walmart (ReliOn): about $25 per vial, sold over the counter without a prescription
- Medicare Part D and Medicaid cover NPH insulin at the federal $35 monthly cap
- Manufacturer patient assistance programs available
Related Reading
For more, see our overview of diabetes treatment, the comparison guide on insulin types, and our deep dive on Tresiba (insulin degludec).
The Bottom Line
Humulin N is intermediate-acting NPH human insulin with onset 1 to 3 hours, peak 4 to 12 hours, and duration 12 to 18 hours, used twice daily or at bedtime for basal coverage. It must be gently rolled to resuspend before each injection. Compared with long-acting analogs (Lantus, Tresiba, Toujeo), NPH causes more nocturnal hypoglycemia and has more variable absorption, but costs only $25 to $50 per vial — a fraction of analog insulin cost. It remains a guideline option in pregnancy, in steroid-induced hyperglycemia, and for cost-sensitive patients. Side effects include hypoglycemia, weight gain, and injection site reactions. Talk to your prescriber about whether NPH is the right basal choice for your situation.
