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Intermediate-Acting Insulin

Reviewed by: HU Medical Review Board | Last reviewed: August 2023

Intermediate-acting insulin is a treatment option for people with type 2 diabetes (T2D). Like other types of insulin, it helps control blood sugar. It starts working within 2 hours of injection and lasts for 18 to 24 hours.1

Insulin is not usually the first treatment for people with T2D. But some people with T2D must take insulin to manage blood sugar. Intermediate-acting insulin can keep blood sugar controlled throughout the day. Talk to your doctor about its risks and benefits.1

How does intermediate-acting insulin work?

Insulin is a hormone produced by the pancreas. It helps move glucose (sugar) from blood into other cells in your body. When you have T2D, your pancreas may not produce enough insulin. Your cells may also not respond well to the insulin your pancreas produces. This leads to high blood sugar.1

Injectable insulin is a common treatment for people with T2D. Several types of insulin are available. They vary in how quickly they take effect and how long they act. Intermediate-acting insulin is one type. It contains substances that delay absorption and prolong action.1-3

"Isophane" insulin is the most common intermediate-acting insulin. It is also called "neutral protamine Hagedorn" (NPH) insulin. NPH insulin generally:4,5

  • Starts working within 2 hours
  • Reaches its highest levels in the blood around 4 to 12 hours
  • Stays effective for 14 to 24 hours

However, these time markers can vary greatly. Even within a single person, absorption of insulin and onset of activity are affected by:5,6

  • Injection site
  • Physical activity
  • Other individual factors


Some examples of intermediate-acting insulin are:1,5,6

  • Humulin® N (NPH insulin)
  • Novolin® N (NPH insulin)

Some insulin treatments combine intermediate-acting insulin with another type of insulin. The combination may provide more precise control of your blood sugar. Examples of these treatments include:1

  • Humalog® Mix 50/50 or 75/25 (NPH insulin and rapid-acting insulin lispro)
  • Novolog® Mix 70/30 (insulin protamine and rapid-acting insulin aspart)
  • Humulin® 70/30 (NPH insulin and regular insulin)

What are the possible side effects?

Side effects can vary depending on the specific insulin you are taking. The most common side effects of intermediate-acting insulin are:5,6

  • Low blood sugar (hypoglycemia)
  • Allergic reactions
  • Injection site reactions, including pitting or thickening of the skin
  • Itching
  • Rash
  • Weight gain
  • Swelling of hands and feet

Low blood sugar can be serious and life-threatening. Talk to your doctor if you notice signs of low blood sugar. These include:5,6

  • Blurry vision
  • Confusion
  • Dizziness
  • Headache
  • Light-headedness
  • Slurred speech
  • Sweating

Allergic reactions can also be serious. Get immediate medical help if you have an allergic reaction. Symptoms include:5,6

  • Breathing problems
  • Rapid heartbeat
  • Rash over your whole body
  • Sweating

Other serious side effects include having a low level of potassium in the blood (hypokalemia) and heart failure. Talk to your doctor about your risk of having these side effects.5,6

These are not all the possible side effects of intermediate-acting insulin. Talk to your doctor about what to expect when taking intermediate-acting insulin. You also should call your doctor if you have any changes that concern you when taking intermediate-acting insulin.

Other things to know

Take intermediate-acting insulin as your doctor describes. It is usually administered under the skin with an injection pen. Good spots to inject include the abdomen, thigh, upper arm, and buttocks.5,6

Your doctor may adjust your dose over time. Do not change your type or dose of insulin unless your doctor tells you to. Check your blood sugar regularly. Talk to your doctor about what level of blood sugar should be your target. Do not take intermediate-acting insulin if you have low blood sugar.5,6

Before beginning treatment for T2D, tell your doctor about all your health conditions and any other drugs, vitamins, or supplements you take. This includes over-the-counter drugs. Other drugs you take or medical conditions you have can make intermediate-acting insulin less safe. Also tell your doctor if you:5,6

  • Have allergies
  • Have any liver, kidney, or heart problems
  • Take thiazolidinediones (TZDs)
  • Are pregnant or plan to become pregnant

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