Insulin Yesterday, Today, and Tomorrow  

Insulin was first identified around 1910 as a substance secreted by the pancreas that influences glucose metabolism. It was named “insuline,” after the Latin word “insula,” meaning “island,” because it was associated with structures in the pancreas called islets of Langerhans. We now know that these structures house beta cells that are responsible for producing insulin and other hormones. 

About a decade later, insulin extracts were successfully used to treat diabetes, first in dogs and then in humans. Eli Lilly and Company was the first to produce insulin commercially in 1922. By 1923, Lilly had begun full-scale production and brought the first insulin, Iletin®, to market. 

Insulin has changed enormously in the century since then, with more transformations on the horizon. Here’s a look at insulin’s past, present, and future. 

Sources of insulin 

From 1922 until the early 1980s, most insulin was derived from pigs and cows. These life-saving insulins were readily available and similar in structure to human insulin. The first animal-derived insulins contained impurities that could trigger allergic reactions and other problems. However, extraction and purification processes improved over time, and insulins became highly purified.  

Then, in the late 1970s, scientists at Genentech and Lilly began engineering bacteria to produce human insulin, called recombinant or synthetic insulin, which typically doesn’t cause allergic reactions. In 1982, Lilly introduced the first commercial synthetic insulin. Since 2006, all insulins sold in the U.S. are synthetic. 

The animal-derived and synthetic insulins of yesterday and today both come from external sources. But in the future, the insulin you need may come from within your own body. Researchers are working to develop artificial and implantable insulin-producing cells and drugs that could protect, regenerate, or reactivate beta cells. Both strategies could someday help your body to produce its own insulin.   

Insulin concentration and dosing 

Insulin concentrations are measured as the number of International Units (IU or just U) of insulin per milliliter (ml) of fluid. An IU is the amount of insulin required to lower blood glucose by a certain amount. This varies from person to person. In the early days, insulins could have any number of U per ml. In other words, the same volume of fluid could have different amounts of insulin — which understandably created confusion in dose calculations. 

In 1972, the U.S. Food and Drug Administration, the American Diabetes Association, and insulin suppliers in the U.S. and Canada agreed to standardize insulin concentration to 100 U/ml. This standardization greatly simplified dosing and reduced errors. Since then, higher concentrations of insulin have been developed and standardized to 200, 300, and 500 U/ml. Higher concentrations mean you can administer smaller volumes to get the same insulin dose.  

Speed and duration of action 

The effects of insulins can be categorized by how quickly they start working and how long they last. For example, animal-derived insulin took about 30 minutes to work and lasted about 8 hours. These time scales made it difficult to match insulin dosing with the body’s needs.  

Scientists soon began modifying insulin to change its speed and duration of action. In the 1930s, drugmakers began combining insulin with protamine to prolong its effects. By the 1950s, they had developed longer-acting formulations, and synthetic insulins allowed for even more modifications.  

Modified forms of synthetic insulin are also called analogs. By 2000, rapid-acting (bolus) and long-acting (basal) insulin analogs became available. Today, we have insulins with a range of speeds and durations of action (Table). Soon, we may have even more. Researchers are working on once-weekly basal insulin formulations that could further reduce the burden of managing diabetes. 

Insulin delivery 

At first, syringes were the only way to administer insulin. Initial versions were made of glass and had to be sterilized and reused. Eventually, single-use plastic versions were developed, along with features to improve comfort, safety, and dosing accuracy.  

In the 1980s, insulin pumps and pens were introduced. Since then, they have become the mainstay choices for diabetes management. Today’s pumps can be paired with continuous glucose monitors (CGMs) via specialty software to partially automate insulin delivery. We also have insulin that can be inhaled instead of injected or infused with a pump. The future will be even more high-tech as manufacturers work on building options to fully automate insulin delivery.  

Past, present, and future 

The debut of insulin in 1922 changed what it meant to have a diabetes diagnosis. During the past century, improvements in insulin therapies and advanced diabetes technologies have significantly improved quality of life factors. With continued innovation, insulin therapy and new approaches to managing blood glucose may bring us to a day when diabetes doesn’t demand a second thought. 

EDITOR’S NOTE: This content was developed independently by T1D Exchange and was supported by a contribution from Eli Lilly and Company.