Humulin NPH
Intermediate-Acting Human Insulin for Diabetes Management
Quick Facts About Humulin NPH
Key Takeaways About Humulin NPH
- Intermediate-acting basal insulin: Humulin NPH provides background insulin coverage for 18–24 hours, with onset in 1–2 hours and peak effect at 4–12 hours after injection
- Must be mixed before use: Roll the pen or vial between your palms 10 times and invert 10 times to ensure uniform suspension – never shake vigorously
- Hypoglycaemia is the main risk: Low blood sugar can occur if the dose is too high, meals are skipped, or exercise is increased – always carry fast-acting glucose
- Rotate injection sites: Inject into the abdomen, thigh, or upper arm and rotate sites within each area to prevent lipodystrophy (skin lumps)
- Storage matters: Keep unopened vials or pens refrigerated (2–8°C); once in use, store at room temperature (up to 30°C) and discard after 28 days
What Is Humulin NPH and What Is It Used For?
Humulin NPH is an intermediate-acting insulin suspension containing human insulin produced by recombinant DNA technology. It is prescribed to help control blood glucose levels in patients with diabetes mellitus, serving as a basal (background) insulin that works over an extended period to keep blood sugar stable between meals and overnight.
Diabetes mellitus is a chronic condition in which the pancreas either produces little or no insulin (type 1) or the body cannot effectively use the insulin it produces (type 2). Insulin is a hormone essential for transporting glucose from the bloodstream into cells, where it is used as energy. Without adequate insulin, glucose accumulates in the blood, leading to hyperglycaemia and potentially serious long-term complications affecting the heart, kidneys, eyes, and nervous system.
Humulin NPH contains human insulin that is structurally identical to the insulin produced by the human pancreas. It is manufactured using recombinant DNA technology, in which the human insulin gene is inserted into Escherichia coli bacteria that then produce the insulin protein. This differs from older animal-derived insulins (porcine or bovine) that have been largely replaced in modern practice. The NPH designation stands for Neutral Protamine Hagedorn, referring to the protamine sulfate that is added to the insulin suspension to slow its absorption after subcutaneous injection.
The protamine sulfate in Humulin NPH forms crystalline complexes with the insulin molecules, which dissolve gradually at the injection site. This results in a delayed onset of action (1–2 hours), a broad peak effect (4–12 hours), and an overall duration of action of approximately 18–24 hours. This pharmacokinetic profile makes Humulin NPH suitable as a basal insulin, providing a steady background level of insulin to control fasting blood glucose and prevent excessive glucose production by the liver between meals.
In clinical practice, Humulin NPH is commonly used as part of a basal-bolus insulin regimen, where it provides basal coverage while rapid-acting or short-acting insulins (such as Humulin Regular or insulin lispro) are administered before meals to manage postprandial glucose spikes. Your doctor will determine the most appropriate insulin regimen based on your individual needs, blood glucose targets, lifestyle, and overall health status. It is important not to change your insulin type, brand, or dose without medical supervision, as different insulins have distinct time-action profiles that can significantly affect blood glucose control.
What Should You Know Before Taking Humulin NPH?
Before starting Humulin NPH, inform your doctor about all medical conditions, medications, and lifestyle factors that may affect your insulin requirements. Certain conditions and drugs can alter how your body responds to insulin, and dose adjustments may be necessary.
Contraindications
Do not use Humulin NPH if you are experiencing an episode of hypoglycaemia (low blood sugar). Using additional insulin during hypoglycaemia will drive blood glucose even lower, which can be life-threatening. Wait until your blood sugar has returned to a safe level before resuming your normal insulin schedule.
Do not use Humulin NPH if you are allergic to human insulin or any of the other ingredients in the formulation, including protamine sulfate, metacresol, phenol, glycerol, dibasic sodium phosphate, or zinc oxide. Allergic reactions can range from mild local skin reactions to severe systemic anaphylaxis.
Humulin NPH cartridges are designed for use only with compatible reusable injection pens. Do not use a 3 ml cartridge in a 1.5 ml pen device. If you need to administer insulin by a different method, consult your healthcare provider. Humulin NPH must never be injected intravenously – it is for subcutaneous use only.
Warnings and Precautions
If your blood glucose is well controlled on your current insulin regimen, you may not notice the warning signs of hypoglycaemia as readily. This phenomenon, known as hypoglycaemia unawareness, can develop gradually, particularly in patients who have had diabetes for many years or who have very tight glycaemic control. It is important to carefully plan your meals, monitor your exercise levels, and test your blood glucose regularly.
Patients who have switched from animal insulin to human insulin have occasionally reported that the early warning symptoms of hypoglycaemia were less pronounced or different from those experienced previously. If you have frequent episodes of hypoglycaemia or difficulty recognising the warning signs, discuss this with your doctor, as your treatment plan may need to be adjusted.
Several factors can alter your insulin requirements. Illness, especially conditions involving vomiting or diarrhoea, can make blood glucose levels unpredictable. Kidney or liver disease can affect how your body processes insulin, potentially leading to prolonged insulin action and increased risk of hypoglycaemia. Changes in physical activity, stress levels, or diet can also necessitate dose modifications. If you consume alcohol, be aware that it can lower blood glucose levels and mask the symptoms of hypoglycaemia.
If you are travelling across time zones, you may need to adjust the timing of your insulin injections and meals. Discuss your travel plans with your diabetes care team in advance so they can help you create an appropriate schedule.
Patients with type 2 diabetes who have a history of cardiovascular disease and are being treated with both pioglitazone and insulin should be monitored for signs of heart failure. Report any unexpected shortness of breath, rapid weight gain, or swelling of the ankles (oedema) to your doctor immediately.
Pregnancy and Breastfeeding
Insulin, including Humulin NPH, can be used during pregnancy and is essential for maintaining blood glucose control to protect both mother and baby. However, insulin requirements typically change during pregnancy: they tend to decrease during the first trimester and increase during the second and third trimesters. Careful monitoring and frequent dose adjustments are necessary throughout pregnancy.
If you are breastfeeding, your insulin dose and diet may need to be adjusted. Insulin does not pass into breast milk and is safe to use while nursing. However, changes in caloric expenditure during breastfeeding can affect blood glucose levels. Consult your doctor or diabetes specialist nurse for personalised guidance.
If you are pregnant, planning to become pregnant, or breastfeeding, always seek medical advice before making any changes to your insulin therapy.
Driving and Operating Machinery
Hypoglycaemia can impair your concentration and reaction time, which may pose a risk when driving or operating machinery. Check your blood glucose before driving, and do not drive if your blood sugar is low or if you feel any symptoms of hypoglycaemia such as dizziness, shaking, or confusion. Keep fast-acting glucose available in your vehicle at all times. If you experience frequent hypoglycaemia or have difficulty recognising the warning signs, discuss with your doctor whether it is safe for you to drive.
How Does Humulin NPH Interact with Other Drugs?
Several medications can increase or decrease the blood glucose-lowering effect of Humulin NPH. Inform your doctor about all prescription drugs, over-the-counter medications, and supplements you are taking, as dose adjustments may be required to maintain safe blood glucose levels.
Drug interactions with insulin are clinically important because they can either potentiate the hypoglycaemic effect (increasing the risk of dangerously low blood sugar) or antagonise it (leading to hyperglycaemia and poor diabetes control). Some medications may also mask the warning symptoms of hypoglycaemia, making it harder to recognise and treat low blood sugar promptly.
Medications That May Increase Insulin Effect (Risk of Hypoglycaemia)
The following medications can enhance the blood glucose-lowering effect of Humulin NPH, potentially leading to hypoglycaemia. Your doctor may need to reduce your insulin dose if you start any of these:
| Drug / Drug Class | Effect on Blood Glucose | Clinical Significance |
|---|---|---|
| ACE inhibitors (e.g. captopril, enalapril) | Increases insulin sensitivity | Monitor blood glucose; dose reduction may be needed |
| MAO inhibitors | Enhances hypoglycaemic effect | Increased risk of severe hypoglycaemia |
| Acetylsalicylic acid (aspirin) | Enhances insulin action at high doses | Monitor closely at analgesic doses |
| Angiotensin II receptor blockers | May improve insulin sensitivity | Monitor blood glucose when starting therapy |
| Oral antidiabetic agents | Additive glucose-lowering effect | Common combination; monitor for hypoglycaemia |
Medications That May Decrease Insulin Effect (Risk of Hyperglycaemia)
The following medications can reduce the effectiveness of Humulin NPH, potentially causing blood glucose levels to rise. Your doctor may need to increase your insulin dose if you start any of these:
| Drug / Drug Class | Effect on Blood Glucose | Clinical Significance |
|---|---|---|
| Corticosteroids (e.g. prednisolone) | Increases blood glucose significantly | May require substantial insulin dose increase |
| Thyroid hormones | Increases glucose production | Adjust insulin when thyroid status changes |
| Growth hormone | Counter-regulatory hormone | Insulin resistance may increase |
| Thiazide diuretics | Impairs glucose tolerance | Monitor blood glucose closely |
| Beta-2 agonists (e.g. salbutamol, terbutaline) | Stimulates hepatic glucose output | Temporary hyperglycaemia possible |
| Danazol | Reduces insulin sensitivity | Dose adjustment usually needed |
| Octreotide / Lanreotide | May increase or decrease insulin needs | Unpredictable; frequent monitoring required |
Beta-Blockers: A Special Consideration
Beta-blockers (such as propranolol, atenolol, or metoprolol) deserve special attention because they can both affect blood glucose levels and mask the typical warning symptoms of hypoglycaemia. Specifically, beta-blockers may suppress the tachycardia (rapid heartbeat) and tremor that many people rely on to detect falling blood sugar. If you are prescribed a beta-blocker alongside insulin, it is essential to monitor your blood glucose more frequently and learn to recognise non-adrenergic symptoms of hypoglycaemia such as confusion, difficulty concentrating, and excessive hunger.
What Is the Correct Dosage of Humulin NPH?
The dosage of Humulin NPH is individualised based on your blood glucose levels, diabetes type, other insulin or medications used, diet, and activity level. Always follow your doctor's instructions precisely. Never adjust your dose without medical guidance.
Insulin dosing is one of the most individualised aspects of diabetes therapy. There is no single correct dose of Humulin NPH – your healthcare team will determine the dose that best controls your blood glucose based on regular monitoring, HbA1c results, and your daily routine. The following information provides general guidance, but your personal dosage may differ significantly.
Adults
Type 1 Diabetes – Basal-Bolus Regimen
Total daily insulin requirement is typically 0.4–1.0 IU/kg/day. In a basal-bolus regimen, approximately 40–50% of the total daily dose is given as basal insulin (Humulin NPH), usually split into one or two injections per day. The remaining 50–60% is given as rapid-acting insulin before meals.
Type 2 Diabetes – Basal Insulin Add-On
When oral medications alone are insufficient, basal insulin is often added. A typical starting dose is 10 IU or 0.1–0.2 IU/kg once daily, usually at bedtime. The dose is then titrated upward every 3–7 days based on fasting blood glucose readings, typically increasing by 2–4 IU at a time until fasting glucose targets are met.
Children and Adolescents
Paediatric Dosing
In children with type 1 diabetes, the total daily insulin requirement is generally 0.5–1.0 IU/kg/day, though prepubertal children may require lower doses (0.5–0.7 IU/kg/day). During puberty, insulin requirements may increase substantially due to growth hormone-mediated insulin resistance, sometimes reaching 1.0–1.5 IU/kg/day. Dosing is always supervised by a paediatric endocrinologist.
Elderly Patients
Dosing in Older Adults
Elderly patients may require lower insulin doses due to reduced renal function, which prolongs insulin clearance, and a higher susceptibility to hypoglycaemia. Blood glucose targets may also be less stringent in older adults to reduce the risk of hypoglycaemia-related falls, fractures, and cardiovascular events. Regular monitoring and cautious dose adjustments are essential.
How to Prepare and Inject Humulin NPH
Humulin NPH is a suspension that must be resuspended before each injection. Follow these steps:
- Wash your hands and disinfect the rubber membrane on the cartridge or vial.
- Resuspend the insulin: Roll the pen or vial between your palms 10 times, then invert it (turn it upside down) 10 times. The suspension should appear uniformly cloudy or milky. Do not use if it contains clumps or white particles adhering to the walls.
- Prime the pen: Attach a new needle, dial 1–2 units, hold the pen with the needle pointing up, and press the injection button until a drop appears at the needle tip.
- Select your dose by dialling the prescribed number of units.
- Choose and clean the injection site: Rotate between the abdomen, thigh, buttocks, or upper arm. Clean the area as directed.
- Inject subcutaneously: Insert the needle as shown by your healthcare provider. Press the injection button fully, then count to 5 before withdrawing the needle to ensure the full dose is delivered.
- Remove and dispose of the needle safely after each injection. Replace the pen cap.
Never share your insulin pen or needles with another person, even if the needle has been changed, as this carries a risk of disease transmission.
Missed Dose
If you miss a dose of Humulin NPH, your blood glucose may rise. Check your blood glucose level and take corrective action as advised by your healthcare provider. Do not take a double dose to make up for a missed injection, as this may cause hypoglycaemia. If you are unsure how to manage a missed dose, contact your diabetes care team for guidance.
Overdose
What Are the Side Effects of Humulin NPH?
Like all medicines, Humulin NPH can cause side effects, although not everyone experiences them. The most significant side effect is hypoglycaemia (low blood sugar). Allergic reactions and skin changes at injection sites can also occur. Understanding these risks helps you recognise and manage them promptly.
The side effects of Humulin NPH are largely shared with other insulin preparations, as they relate to the pharmacological action of insulin itself and the method of administration. The most clinically important adverse effect is hypoglycaemia, which can range from mild discomfort to a medical emergency.
Hypoglycaemia (Very Common)
- Shaking, trembling
- Sweating, cold sweats
- Rapid heartbeat (palpitations)
- Hunger, nausea
- Headache, dizziness
- Fatigue, weakness
- Nervousness, irritability
- Difficulty concentrating, confusion
Local Allergic Reactions (Common)
- Redness at the injection site
- Swelling at the injection site
- Itching at the injection site
Skin Changes at Injection Site (Uncommon)
- Lipohypertrophy (thickening of fat tissue, lumps)
- Lipoatrophy (shrinkage of fat tissue, indentations)
- Cutaneous amyloidosis (protein deposits under the skin)
Systemic Allergic Reactions (Very Rare)
- Generalised rash across the body
- Drop in blood pressure
- Difficulty breathing, wheezing
- Rapid heartbeat
- Excessive sweating
If you experience any signs of a systemic allergic reaction (widespread rash, difficulty breathing, swelling of the face or throat, rapid heartbeat), seek emergency medical attention immediately. This type of reaction is extremely rare but can be life-threatening.
Oedema (swelling of the ankles, feet, or hands due to fluid retention) has been reported, particularly when insulin therapy is initiated or when treatment is intensified to improve glycaemic control. This is usually temporary and resolves as the body adjusts to insulin therapy.
Managing Hypoglycaemia
Hypoglycaemia occurs when blood glucose drops below approximately 4 mmol/L (70 mg/dL). Common causes include taking too much insulin, skipping or delaying meals, exercising more than usual, drinking alcohol, or illness (particularly vomiting or diarrhoea).
If you experience symptoms of mild to moderate hypoglycaemia:
- Immediately consume 15–20 grams of fast-acting carbohydrate (e.g. 3–4 glucose tablets, half a glass of fruit juice, or a sugary drink)
- Wait 15 minutes and recheck your blood glucose
- If still below 4 mmol/L, repeat the treatment
- Once blood glucose normalises, eat a longer-acting carbohydrate snack (e.g. a sandwich, biscuits, or fruit)
Severe hypoglycaemia, characterised by confusion, loss of consciousness, or seizures, requires emergency treatment with glucagon injection (administered by a trained companion) and immediate contact with emergency services. Every person using insulin should ensure that their family members, close friends, and colleagues know how to recognise and treat severe hypoglycaemia.
Managing Hyperglycaemia and Diabetic Ketoacidosis
Hyperglycaemia (high blood sugar) can occur if you miss insulin doses, take less than prescribed, eat more than your meal plan allows, or are ill or under stress. Symptoms develop gradually over hours or days and include increased thirst, frequent urination, fatigue, drowsiness, loss of appetite, flushed face, fruity-smelling breath, nausea, and vomiting.
If left untreated, hyperglycaemia can progress to diabetic ketoacidosis (DKA), a life-threatening condition characterised by heavy, rapid breathing and a fast pulse. DKA requires immediate medical treatment. If you experience these symptoms, seek emergency medical care without delay.
How Should You Store Humulin NPH?
Proper storage of Humulin NPH is essential to maintain its effectiveness. Unopened products should be refrigerated at 2–8°C. Once in use, store at room temperature (up to 30°C) and use within 28 days. Never freeze insulin.
Keep Humulin NPH out of the sight and reach of children at all times. Store unopened cartridges, vials, or pre-filled pens in a refrigerator at 2–8°C (36–46°F). Do not place them in or near the freezer compartment, and never freeze insulin. Frozen insulin loses its effectiveness and must be discarded.
The cartridge, vial, or pen that you are currently using should be stored at room temperature, not exceeding 30°C (86°F), and should be used within 28 days of first use. Do not return the in-use pen or cartridge to the refrigerator, as temperature fluctuations can promote the formation of crystals that affect dosing accuracy.
Protect insulin from direct heat, sunlight, and extreme cold. Do not leave it in a car on a hot or cold day, and do not carry it in checked luggage when flying (the cargo hold may reach freezing temperatures). When travelling, use an insulated pouch to keep your insulin at an appropriate temperature.
Before each injection, inspect the insulin visually. After resuspension, Humulin NPH should appear uniformly cloudy or milky white. Do not use it if the suspension contains clumps, if solid white particles stick to the bottom or walls of the container giving it a frosted appearance, or if the suspension does not become uniformly cloudy after gentle mixing.
Always check the expiry date printed on the label and carton before use. Do not use Humulin NPH after the expiry date, which refers to the last day of the stated month. Dispose of expired or unused insulin according to local regulations – do not throw it in household waste or flush it down the drain. Ask your pharmacist about proper disposal methods.
What Does Humulin NPH Contain?
Humulin NPH contains human insulin as the active substance, produced using recombinant DNA technology. It also contains several excipients that stabilise the formulation and extend the duration of action.
The active substance is human insulin (rDNA origin). Each millilitre of Humulin NPH suspension contains 100 international units (IU) of human insulin. The insulin is produced in the laboratory using recombinant DNA technology, where the human insulin gene is expressed in Escherichia coli bacteria. The resulting insulin is structurally identical to the hormone produced by the human pancreas, distinguishing it from older animal-derived insulin preparations.
The other ingredients (excipients) in Humulin NPH are:
- Protamine sulfate – forms complexes with insulin to delay absorption and extend the duration of action
- Metacresol – antimicrobial preservative
- Phenol – antimicrobial preservative
- Glycerol – tonicity agent to make the solution isotonic with body tissues
- Dibasic sodium phosphate heptahydrate – buffering agent to maintain pH stability
- Zinc oxide – stabilises the insulin hexamer structure
- Water for injections – solvent
- Sodium hydroxide or hydrochloric acid – may be added during manufacture for pH adjustment
This medicine contains less than 1 mmol sodium (23 mg) per dose and is considered essentially sodium-free. Each cartridge contains 300 units (3 ml) of insulin suspension. Cartridges are available in packs of 5.
Humulin NPH is manufactured by Eli Lilly. It is approved in numerous countries worldwide and may be marketed under different brand names in different regions, including Humulin NPH, Humulin N, and Humulin I, depending on the country.
Frequently Asked Questions About Humulin NPH
Humulin NPH is an intermediate-acting insulin that takes 1–2 hours to start working, peaks at 4–12 hours, and lasts up to 18–24 hours. It provides basal (background) insulin coverage. Rapid-acting insulins, such as insulin lispro (Humalog) or insulin aspart (NovoRapid), begin working within 15–30 minutes and last only 3–5 hours. They are used to cover meals and correct high blood sugar. Many people with diabetes use both types together as part of a basal-bolus regimen.
Store unopened Humulin NPH in the refrigerator at 2–8°C. Never freeze it. Once you start using a cartridge or pen, keep it at room temperature (up to 30°C) and use it within 28 days. Do not return the pen you are using to the refrigerator. Protect from direct heat and sunlight, and always check the expiry date before use.
An overdose of Humulin NPH can cause hypoglycaemia (low blood sugar). If you experience mild symptoms such as shaking, sweating, or hunger, immediately consume 15–20 grams of fast-acting carbohydrate (glucose tablets, juice, or sugary drink), then eat a longer-acting snack. For severe hypoglycaemia with confusion or loss of consciousness, a glucagon injection should be administered and emergency services contacted immediately.
Yes, insulin therapy, including Humulin NPH, is safe and essential during pregnancy for maintaining blood glucose control. However, insulin requirements change throughout pregnancy – they typically decrease during the first trimester and increase during the second and third trimesters. Close monitoring by your healthcare team and frequent dose adjustments are necessary to protect both mother and baby.
Humulin NPH is a suspension containing insulin bound to protamine sulfate. When the pen is not in use, the insulin-protamine particles settle to the bottom. Rolling the pen between your palms 10 times and inverting it 10 times ensures the suspension is uniformly mixed, resulting in a consistent milky-white appearance. This step is critical for accurate dosing. Never shake the pen vigorously, as this creates air bubbles that can affect the dose.
Common early signs of hypoglycaemia include tiredness, rapid heartbeat, nervousness and shaking, nausea, headache, and cold sweats. More severe signs include confusion, difficulty speaking, blurred vision, and loss of consciousness. If you notice any early symptoms, immediately consume fast-acting glucose. Always carry glucose tablets or a sugary snack. Make sure family members and colleagues know how to recognise the signs and how to help you.
References and Medical Sources
This article is based on the following peer-reviewed sources and international medical guidelines:
- American Diabetes Association. Standards of Care in Diabetes – 2024. Diabetes Care. 2024;47(Supplement 1):S1–S321. doi:10.2337/dc24-SINT
- Davies MJ, Aroda VR, Collins BS, et al. Management of Hyperglycaemia in Type 2 Diabetes, 2022. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2022;45(11):2753–2786. doi:10.2337/dci22-0034
- World Health Organization. WHO Model List of Essential Medicines – 23rd List, 2023. Geneva: WHO; 2023. Insulin human is listed as an essential medicine.
- National Institute for Health and Care Excellence (NICE). Type 1 diabetes in adults: diagnosis and management. NICE guideline [NG17]. Updated 2022.
- National Institute for Health and Care Excellence (NICE). Type 2 diabetes in adults: management. NICE guideline [NG28]. Updated 2022.
- European Medicines Agency. Humulin NPH – Summary of Product Characteristics. Available at: ema.europa.eu
- Eli Lilly and Company. Humulin NPH Patient Information Leaflet. Last revised 2024.
- Holman RR, Paul SK, Bethel MA, et al. 10-Year Follow-up of Intensive Glucose Control in Type 2 Diabetes. N Engl J Med. 2008;359:1577–1589. doi:10.1056/NEJMoa0806470
Editorial Team
This article was written and reviewed by the iMedic Medical Editorial Team, which includes licensed physicians specialising in endocrinology, diabetology, and clinical pharmacology. All content follows the GRADE evidence framework and is regularly updated to reflect the latest international guidelines.
Specialist physicians with clinical experience in diabetes management and insulin therapy. All writers hold current medical licences and have documented expertise in endocrinology.
Independent panel of senior clinicians who verify medical accuracy against current evidence. All claims are cross-referenced with ADA, EASD, WHO, and NICE guidelines.
All medical information on iMedic is evidence-based (Level 1A where available), independently reviewed, and free from commercial influence. We receive no pharmaceutical funding and have no conflicts of interest. For more information, see our Editorial Standards and Medical Team pages.