A History of Insulin Development and Insulin Delivery Systems

August 23, 2022 - In recent years, the costs of prescription drugs have increased dramatically. One of the most notable drugs with high prices is insulin. Understanding the basic uses of insulin and common delivery methods may contribute to an in-depth understanding of the issue.

A publication in the Mayo Clinic Proceedings stated that the cost of insulin in the United States is ten times higher than that in other countries. This high cost of insulin is a common contributor to poor medication adherence and adverse outcomes.

“The tragedy of insulin prices and the rationing that follows is not something that happens in other developed countries, but it is common in the United States. A study conducted at Yale University found that 25% of patients with diabetes ration insulin because of the high cost. There are 30 million patients with diabetes in the United States, and approximately 25% (7.4 million Americans) need insulin. For the 1.3 million patients with type 1 diabetes, insulin is as vital as air and water,” researchers said in the article.

Insulin Basics

Information from the American Diabetes Association (ADA) states that insulin is made by the beta cells inside the pancreas. In a healthy person, insulin is produced at each meal and is used to help process the glucose from food and use it as energy.

The CDC classifies patients with type 1 diabetes as patients whose pancreas does not make any insulin or makes very little insulin. This disorder most commonly develops in children but can occur at any age. Approximately 5–10% of diabetes patients are classified as type 1.

While there is no cure for type 1 diabetes, there are ways to manage the symptoms of the disease.

“People with type 2 diabetes make insulin, but their bodies don't respond well to it. Some people with type 2 diabetes need diabetes pills or insulin shots to help their bodies use glucose for energy,” stated the ADA in their article.

According to the International Journal of Pharmaceutical Investigation, about 552 million people will have diabetes by 2030.

The Diabetes Therapy Journal states that insulin was discovered approximately 100 years ago in 1921. However, the first patent on insulin did not occur until 1923.

Types of Insulin

The type and dose of insulin are based on activity level, diet, age, and insulin absorption rate.

To properly understand the effects of insulin, it is essential to become familiar with the terminology. Insulin onset refers to the time it takes for insulin to lower blood sugar. Peak time refers to the point at which insulin is maximum strength. Finally, duration is the length of time insulin works to reduce blood sugar.

The CDC identifies seven different kinds of insulin: rapid-acting, rapid-acting inhaled, regular/short-acting, intermediate-acting, long-acting, ultra-long acting, and premixed.

For insulin to correctly enter the bloodstream, it must be injected into the fat under the skin.

Types of rapid-acting insulin include insulin aspart, glulisine, and lispro. The peak time for this kind of insulin is between one and two hours after injection. Its onset occurs approximately 15 minutes after injection, lasting between two and four hours.

Humulin R, Novolin R, and Velosulin R are all forms of regular or short-acting insulin. The ADA states that the onset for this type of insulin is 30 minutes after injection, while the peak occurs between hours two and three. The duration is a minimum of three hours and a maximum of six hours.

Intermediate-acting insulin such as Humulin N and Novolin N have an onset of between two and four hours, a peak between four and 12 hours, and a duration of up to 18 hours.

Long-acting insulin works for approximately 24 hours and does not become effective until several hours after injection. Degludec, detemir, and glargine are all forms of this insulin.

Ultra-long-acting insulin begins to work six hours after injection and lasts a minimum of 36 hours. This type of insulin, including glargine U-300, does not have a peak.

Premixed insulin is often recommended for patients struggling to draw up the appropriate insulin dose.

Common Insulin Delivery Methods

The CDC states that there are four main insulin delivery mechanisms. The medication used depends on the medication regimen and the patient’s lifestyle.

Syringe

The first delivery mechanism is via syringe. This form of insulin delivery is self-explanatory. The vial of insulin is given to the patient, and they use a syringe to draw up and inject the insulin as prescribed by their physician. Benefits of injection include less necessary training and reduced costs. However, syringes require the calculation of insulin and adequately inserting the syringe.

The Diabetes Therapy Journal describes early insulin syringes as “big and heavy reusable syringes with plungers, barrels, and long large-bore needles were used for insulin delivery.”

To prevent infection, these items were boiled before each reuse. The first insulin syringe was manufactured in 1924. It wasn’t until 1955 that an all-plastic mono-eject needle was introduced.

“By the mid-1960s, disposable plastic syringes from numerous vendors were available on the market. These syringes reduced pain and the incidence of needle-associated infections,” stated investigators in Diabetes Therapy.

The publication went on to say, “even though ‘conventional’ syringe technology has become less popular in the current era, vials and syringes have remained as the only option for insulin delivery for more than 50 years.”

Although there are multiple benefits to the syringe injection method, there are a few disadvantages. One of the main disadvantages is a lack of accuracy due to required calculations. Additionally, it can impair the quality of life due to the requirement of multiple daily injections.

Insulin Pen

Conversely, an insulin pen also acts as an injection, but rather than the patient having to draw up the dose themselves, the pen is preset on the appropriate amount. Pens are more portable and have smaller, less painful needles but may be more costly and require specific kinds of insulin.

The International Journal of Pharmaceutical Investigation states that the first insulin pen was developed in 1985 by NovoNordisk. Over the past few years, advancements have been made to make insulin pens more user-friendly.

“Recently developed pen needles are shorter and thinner (31–32 G × 4–5 mm), less painful, and requires less thumb force and time to inject insulin resulting in improved patient satisfaction,” wrote scientists in the publication.

Insulin Pump

An insulin pump is quickly becoming a more common method of insulin delivery. The pump is a small monitor where you can enter the appropriate dose based on what you ate. The monitor is connected to a small plastic tube inserted into the stomach or upper arm.

According to the International Journal of Pharmaceutical Investigation, “the first portable insulin pump was invented by Kadish in 1963; however, it was limited by its size and technical issues.” 

It wasn’t until 1979 that a commercial pump was introduced.

According to the Cleveland Clinic, “many people find that insulin pumps are a more flexible option than insulin pen injections. Insulin pumps don’t have to be permanent, and you can switch to another insulin management method at any time.”

The Cleveland Clinic also suggests that using an insulin pump may depend on lifestyle. It recommends the pump for people who have delays in food absorption, are active, are severely impacted by low blood sugar, or are diabetic and planning to become pregnant.

Why Are Costs Inflated and How to Address Them?

An article in the Mayo Clinic Proceedings states that “the three main reasons cited by pharmaceutical companies for the high cost of new prescription drugs do not apply to insulin.”

A high development cost does not apply to this medication as it was developed approximately 100 years ago. In addition, the cost increase is not due to inflation as the prices have risen exponentially faster than inflation. Finally, the excuse that increased costs encourage innovation is invalid. Innovation, in this case, is less valuable than accessibility.

Researchers in the article proposed multiple solutions to reduce costs and broaden accessibility, including value-based reimbursement and pricing, more straightforward introductions of biosimilars, and patent reforms.