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What is the difference between regular insulin and lispro (Humalog)?

Medically reviewed by Carmen Pope, BPharm. Last updated on June 16, 2022.

Official answer

  • Insulin lispro is an analog insulin.
  • Lispro is made by genetically modifying the structure of human insulin to allow it to be absorbed more quickly and last for a shorter length of time than regular insulin.
  • This means it can be administered 15 minutes before or with a meal which makes it more convenient for people with diabetes, and also safer.
  • Lispro also has a shorter duration of effect than regular insulin. This means lispro better mimics how insulin is naturally released in response to food in people without diabetes.
  • Side effects such as low blood sugar levels (hypoglycemia) are less likely with lispro than regular insulin.

Although both regular insulin and insulin lispro are man-made and their structures mimic naturally occurring human insulin, there are differences in the way they are made.

  • Regular insulin contains hexamers of insulin crystallized around a zinc molecule. To be absorbed into the bloodstream regular insulin must first diffuse from the injection site and dissociate into dimers and monomers. Diffusion is slow, requiring 50 to 90 minutes which limits insulin absorption.
  • Insulin lispro is an analog insulin. An analog insulin is a genetically modified insulin. Human insulin is made up of a linked A and B polypeptide chains and insulin lispro is made by switching the sequence of two beta-chain amino acids: the proline at B-28 is switched with the lysine at B-29. This results in more rapid dissolution of the insulin to a dimer and then to a monomer which means it is absorbed more rapidly after subcutaneous injection and lasts for less than five hours.

Although one unit of insulin lispro has the same glucose-lowering effect as one unit of regular insulin, it has:

  • A faster rate of absorption after injection
  • An earlier and greater insulin peak
  • A more rapid post-peak decrease.

Insulin lispro only needs to be given 15 minutes before or immediately after a meal whereas regular insulin needs to be administered 30 minutes before a meal. This is an important safety consideration because if insulin is administered to a diabetic, and then they forget to eat or their meal is delayed, they could develop hypoglycemia.

Because insulin lispro has a shorter duration of action than regular insulin, this reduces the risk of low blood sugars immediately following a meal (postprandial hypoglycemia). Insulin analogs are also less likely to cause hypoglycemia (low blood sugar levels) in general.

A longer-acting form of insulin lispro is also available called insulin lispro protamine suspension. Humalog 75:25 contains insulin lispro protamine suspension as the intermediate-acting insulin and insulin lispro as the short-acting insulin.

What is insulin?

Insulin is a hormone that is produced naturally in our bodies. Its main role is to allow cells throughout the body to uptake glucose (sugar) and convert it into a form that can be used by these cells for energy. Without insulin, we cannot survive, and death from diabetes was a common occurrence until insulin was discovered in the early 1900s by Frederick Banting and Charles Best.

What is the difference between analog insulin and regular insulin?

An insulin analog is a human insulin that has been modified in a certain way to overcome some problems that occur with regular short-acting insulin. Problems such as:

  • A slower onset of effect which means regular insulin must be given 30 minutes before a meal, which may cause low blood sugar levels if a meal is delayed for any reason
  • Safety concerns if a meal is not eaten within 30 minutes of administration
  • A long duration of action
  • A risk of post-meal low blood sugar (postprandial hypoglycemia) 4 to 6 hours after a meal
  • Risk of high insulin levels.

Insulin analogs, by comparison, have:

  • A much quicker onset of action which means they can be given within 15 minutes of a meal or with food
  • A shorter duration of action which lessens the risk of postprandial hypoglycemia.

Insulin lispro (Humalog)

A rapid-acting insulin that:

  • Starts working within 0 to 15 minutes after administration
  • Peaks in 30 to 90 minutes
  • Keeps working for less than five hours (usually two to four hours).

Humalog Mix

Humalog mix combines short-acting insulin with longer-acting insulin. Protamine (a fish protein) is added to insulin lispro to delay its absorption and allow it to act for longer in the body. This means people do not have to inject themselves as often.

Protamine insulins are cloudy and need to be remixed thoroughly before each injection. Humalog Mix is available as:

  • Humalog 50:50 which contains 50% insulin lispro protamine and 50% insulin lispro
  • Humalog 75:25 which contains 75% insulin lispro protamine and 25% insulin lispro.

Regular insulins

Humulin R and Novolin R are regular insulins. They are short-acting insulins that:

  • Start to work within 30 minutes after injection
  • Peak in 2 to 3 hours
  • Keep working for up to 8 hours.

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