Types of Insulin: Pharmacokinetics

Insulins are classified by their onset of action:

Rapid-acting insulins are nearly immediately active and tend to have a quick peak and short duration.

Short-acting insulins take a little longer to peak and provide a longer time of action before clearing from the body.

Intermediate-acting and intermediate to long-acting insulins have a longer time to onset and peak and stay in the body longer.

Long-acting may take longer till onset and provides coverage without a significant peak for up to and, in some cases, longer than 24 hours.

There are also combination products. Insulins are typically provided as 100 units per mL, or “U-100”, but U-300 and U-500 concentrations are also available.

Recombinant Human Insulin Versus Insulin Analogs

Regular and NPH are human insulins; the others we will discuss are insulin analogs.

Animal-derived insulins are no longer used in the United States, and synthetic insulins, either recombinant human insulin or insulin analogues, are used exclusively. Insulin analogues are the preferred preparation. The insulin analogues are preferred because:

The purpose of insulin therapy is to attain glycemic control without hypoglycemia and to mimic as closely as possible endogenous basal and post-prandial insulin secretion.

The insulin analogues are better at replicating endogenous insulin secretion patterns than recombinant human insulin.

Insulin analogues have been genetically engineered to change absorption, distribution, metabolism, and excretion, in order to provide advantages when attaining glycemic control.

Two examples of the advantages of the pharmacokinetic profiles of the insulin analogues:

Lispro insulin has a quicker onset of action, and a longer duration of action than regular insulin and these effects make it more useful than regular insulin for post-prandial glucose control.

The long-acting insulin analogues, in contrast, have a slower rate of absorption and a longer duration of action and these pharmacokinetic properties have been shown to reduce the incidence of nocturnal hypoglycemia.

Injection Technique and Insulin Efficacy

The amount of insulin that is absorbed can vary significantly from patient to patient and from dose to dose, and there can be intra-patient variation in absorption, as well. The pharmacokinetics of insulin and thus its actions and effectiveness can be influenced by many factors related to the injection process, and optimal insulin injection technique can improve glycemic control.

Injection site: Insulin can be injected in the abdominal wall, buttocks, upper arms, and upper legs, and the speed of insulin absorption differs between these sites: it is fastest in the abdominal wall, the slowest in the buttocks, and legs, and in between those two areas for the upper arms. All of these areas can be used, but a planned rotation can help reduce day-to-day changes in blood glucose, it can reduce HbA1c and reduce the total daily insulin dose, and prevent lipoatrophy, lipohypertrophy, and subcutaneous scarring. Lipohypertrophy occurs in approximately 50% of diabetic patients and injecting insulin into a lipohypertrophic area can significantly reduce insulin absorption and cause erratic insulin absorption.

Injection angle and technique: The angle of injection should be 90°. Using or not using a lifted skin fold technique will depend on the length of the needle, and if the needle is at least 4 mm, lifting a fold of skin is not needed. When using an insulin pen, the needle should be left in place for 5-10 seconds to ensure the dose is delivered and to avoid insulin leaking from the injection site.

Self-injection of insulin is not complicated, but newly diagnosed type 1 diabetics will need to be taught the proper techniques, including needle size, angle of injection, and other factors as they apply to the patient. Physicians, nurses, and pharmacists can perform the necessary patient teaching.