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Insulin human isophane (NPH)

Intermediate-acting human insulin

ATC code: A10AC01

Brand names: Humulin N, Novolin N

Updated · Methodology

Indications

A

Insulin-dependent type 2 diabetes mellitus

First line

In type 2 diabetes NPH remains a workable way to start basal therapy: one evening injection alongside metformin covers morning hyperglycaemia. Spain's redGDPS treats NPH as an equivalent alternative to analogues for glycaemic control, with the difference showing up in nocturnal hypoglycaemia, which is commoner on NPH. For someone living alone, working nights or with impaired hypoglycaemia awareness that consideration outweighs the price difference. The sulfonylurea is revisited when insulin starts; metformin stays. The suspension is mixed before injection, and this is not a formality: an unmixed suspension changes the dose from shot to shot.

Sources

  1. AEMPS: Ficha técnica Humulina NPH KwikPen 100 UI/ml suspensión inyectable (2020)
  2. redGDPS: Guía de diabetes tipo 2 para clínicos (2024)

ICD-10: E11.9 · ICD-11: 5A11

A

Type 1 diabetes mellitus

Second line

NPH covers the basal requirement in type 1 diabetes where long-acting analogues are unavailable or unaffordable. The regimen needs two injections a day, and the pronounced 4–8 hour peak produces more nocturnal hypoglycaemia than glargine or degludec. Hence the practice of moving the evening dose closer to bedtime so the peak does not fall in the middle of the night. The AEMPS Humulina NPH label requires resuspending the suspension before every injection. For someone counting carbohydrates on an irregular schedule a basal analogue is more convenient, but on control NPH does not fall behind.

Sources

  1. AEMPS: Ficha técnica Humulina NPH KwikPen 100 UI/ml suspensión inyectable (2020)
  2. ADA: Standards of Care in Diabetes 2025 (2025)

ICD-10: E10 · ICD-11: 5A10

How to read tiers A–F
  • AStrong evidence – first or second line in international guidelines
  • BRecommended in selected cases
  • CStudy data contradict each other
  • DBenefit not proven, no documented harm
  • FDocumented harm, or risk without benefit

Mechanism of action

NPH is human insulin precipitated with protamine and zinc into crystals. From the subcutaneous depot the crystals dissolve gradually: action starts in 1–2 hours, peaks at 4–8 hours and lasts 12–18 hours. That peak is the key difference from basal analogues – with an evening injection it lands at night and explains frequent nocturnal hypoglycaemia. The suspension is resuspended with gentle movements before injection; otherwise the dose becomes a lottery, with too much or too little protamine insulin drawn into the syringe.

Safety

Contraindications

  • Hypoglycaemia
  • Hypersensitivity to insulin or to any excipient of the product

Serious adverse effects

  • Severe hypoglycaemia with loss of consciousness and seizures
  • Hypokalaemia in overdose, up to rhythm disturbance
  • Anaphylaxis and generalised insulin allergy
  • Oedema and decompensated heart failure when combined with pioglitazone

Common adverse effects

  • Hypoglycaemia: sweating, tremor, palpitations, hunger, confusion
  • Injection site reactions: redness, swelling, itching
  • Lipohypertrophy when injections stay in one spot
  • Weight gain early in treatment

Pregnancy: can you take Insulin human isophane (NPH)?

Insulin does not cross the placenta and remains the mainstay of glycaemic control in pregnancy. Requirements shift by trimester: usually lower in the first, rising from the second, and falling sharply after delivery. The dose is revisited at every stage.

Breastfeeding: can you take Insulin human isophane (NPH)?

The label sets no restriction during breastfeeding: insulin is broken down in the infant's gut and does not reach the bloodstream. Insulin requirements often fall during lactation, so the dose is retitrated.

Calculate RID

Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.

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Frequently asked

What is Insulin human isophane (NPH) used for?

Insulin human isophane (NPH) is evaluated for the following indications with varying evidence strength: Type 1 diabetes mellitus (evidence tier A), Insulin-dependent type 2 diabetes mellitus (evidence tier A). See the full indication matrix with dosing and citations above on this page.

What are the side effects of Insulin human isophane (NPH)?

Common side effects of Insulin human isophane (NPH) (≥ 1 in 100): Hypoglycaemia: sweating, tremor, palpitations, hunger, confusion, Injection site reactions: redness, swelling, itching, Lipohypertrophy when injections stay in one spot, Weight gain early in treatment. See the Safety section for uncommon and serious reactions.

Is Insulin human isophane (NPH) safe during pregnancy?

Insulin does not cross the placenta and remains the mainstay of glycaemic control in pregnancy. Requirements shift by trimester: usually lower in the first, rising from the second, and falling sharply after delivery. The dose is revisited at every stage.

Is Insulin human isophane (NPH) compatible with breastfeeding?

The label sets no restriction during breastfeeding: insulin is broken down in the infant's gut and does not reach the bloodstream. Insulin requirements often fall during lactation, so the dose is retitrated.

Who should not take Insulin human isophane (NPH)?

Insulin human isophane (NPH) is contraindicated in: Hypoglycaemia; Hypersensitivity to insulin or to any excipient of the product. Full list in the Safety section.

Other drugs in this group

Insulin lispro, Linagliptin, Liraglutide, Metformin, Sitagliptin + Metformin, Empagliflozin, Insulin aspart, Pioglitazone