Isophane (NPH) insulin !

Human insulin bound to protamine and zinc so it dissolves slowly under the skin. The classic cloudy, intermediate-acting basal insulin.

Updated 2026-11-01

Class: Insulins
Receptor: Insulin receptor
ATC code: A10AC01
WHO Model List of Essential Medicines

Also called: NPH insulin, intermediate-acting human insulin, insulin human isophane

Insulin receptorIsophane (NPH) insulin

The figure shows human insulin bound to site 1 of an insulin receptor fragment. NPH releases this same human insulin, so the binding is identical; the protamine only slows absorption.

Target in 3D: Insulin receptor. PDB structure 4OGA (RCSB PDB, public domain). View the structure at RCSB PDB

Mechanism of action

NPH is ordinary human insulin crystallized with protamine and zinc into a suspension. Under the skin the crystals dissolve gradually, so insulin reaches the blood more slowly and acts longer than regular insulin. Once free, it activates the insulin receptor tyrosine kinase like the body's own insulin: GLUT4 moves to the membrane in muscle and fat, and the liver stores glycogen and releases less glucose.

Protamine–zinc crystals dissolve slowly under the skin
Free human insulin binds and activates the insulin receptor
Muscle and fat take up glucose; the liver releases less
Gives a basal effect between meals and overnight

Pharmacokinetics

Absorption: Subcutaneous only; absorption is slower and more variable than with regular insulin.
Elimination: Cleared mainly by the liver and kidney, like endogenous insulin; kidney impairment raises the risk of hypoglycemia.
Onset and duration: Intermediate acting: slower onset than regular insulin, a clear peak several hours after the injection and a shorter duration than the long-acting analogues.

Indications

Basal insulin in type 1 diabetes, combined with a mealtime insulin Type 1 diabetes mellitus →
Basal insulin in type 2 diabetes when other drugs are not enough Type 2 diabetes mellitus →
Diabetes in pregnancy, including gestational diabetes not controlled by diet Gestational diabetes mellitus →

Adverse effects

Common

Hypoglycemia, especially at the time of its peak (often at night)
Weight gain
Lipohypertrophy at repeated injection sites
Low potassium

Contraindications

During an episode of hypoglycemia
Hypersensitivity to insulin or to an excipient of the preparation

Key interactions

Beta-blockers, clonidine: Can blunt the warning signs of hypoglycemia.
Other glucose-lowering drugs, alcohol: Raise the risk of hypoglycemia (alcohol can also raise glucose).
Corticosteroids, thiazide diuretics, atypical antipsychotics, niacin: Reduce the glucose-lowering effect, so insulin needs go up.
Thiazolidinediones (pioglitazone): Fluid retention that can cause or worsen heart failure.

What is monitored

Capillary blood glucose, including before bed and on waking
HbA1c
Injection sites
Potassium in patients at risk

Administration and safety

Subcutaneous only: it is a suspension and is never given intravenously.
Rolled gently between the hands until evenly milky before each dose; not shaken hard.
Can be mixed in one syringe with regular insulin or a rapid analogue, following the local protocol.
Look-alike risk: check the label, since several human insulins share similar names and packaging.

Nursing care

Before: blood glucose, meal plan and timing of the dose.
During: watch for hypoglycemia at the time of the peak, especially at night.
Rotate injection sites and check for lumps (lipohypertrophy).
Teach the signs of hypoglycemia and how to treat it with fast-acting sugar.
Check that the suspension is uniformly cloudy; clumps or frosting mean it is not used.

Pregnancy and breastfeeding

Human insulins, including NPH, are a standard choice for diabetes in pregnancy; needs change by trimester, so glucose is checked often.

Test yourself

Think of the answer, then tap the question to see it.

Why does NPH insulin look cloudy, unlike regular insulin?

It is a suspension of insulin crystallized with protamine and zinc. The particles settle, so it is rolled before use; regular insulin is a clear solution.

Can NPH be given intravenously in ketoacidosis?

No. Only regular (clear) insulin is used intravenously; NPH is a suspension for subcutaneous use.

Compared with glargine, what is the main drawback of NPH as a basal insulin?

It has a clear peak and more variable absorption, so night-time hypoglycemia is more common; glargine has almost no peak.

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Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: Human Insulin Injection: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed., ch. 51 (McGraw Hill, 2023); Insulin in complex with Site 1 of the human insulin receptor (RCSB Protein Data Bank, 2014); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).

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Representative model, for educational purposes only.