FTLOScience
FTLOScience

Insulin: From Inspiring Discovery to Deadly Expense

By Published On: August 24, 2020Last Updated: November 23, 2022

Half a billion people today suffer from diabetes, a disease that causes high blood glucose levels. Although no cure exists as yet, the remarkable discovery and subsequent development of insulin injections have allowed millions of diabetics to lead normal lives. However, the high costs of insulin treatment in the U.S. have made this life-saving drug inaccessible to certain patients.

Insulin as a treatment for type 1 diabetes was discovered more than 100 years ago. Since then, the drug has gotten cheaper to manufacture every year, yet U.S. prices for insulin keep increasing. Insulin in the U.S. is expensive because pharmaceutical companies offer rebates to pharmacies and insurance companies, who hold the profits instead of passing the discount on to the patient. The result is that a month’s supply that costs three dollars overseas can cost more than a thousand in the U.S.

Insulin and Diabetes

Glucose is a simple molecule that serves as a source of energy and carbon. In humans, we obtain glucose from digesting carbohydrates in our food. Once glucose enters our bloodstream, our pancreas produces insulin in response, which tells our cells to absorb the glucose in the blood. Diabetes is a disease in which the body stops regulating blood glucose levels—also known as ‘blood sugar’—properly. Most cases of diabetes can be classified into either type 1 or type 2.



Type 1 and Type 2

Type 1 diabetes often occurs spontaneously in younger patients, in which the immune system attacks our insulin-producing cells. This results in the pancreas failing to produce insulin, which means the body is unable to regulate the amount of sugar in the blood. Some individuals are genetically more susceptible to type 1 diabetes, which can be triggered by external, environmental factors such as diet.

In type 2 diabetes, insulin is produced by the pancreas, however, it is not recognized by our cells. The receptors that signal glucose uptake become ‘desensitized’ to insulin, although the exact mechanism of this is not known. Although genetics also play a role in type 2 diabetes, obesity, poor diet and a lack of exercise increase its risk in individuals. Interestingly, it has been shown that childhood difficulties (abuse, neglect, etc.) increase the chance of an individual developing type 2 diabetes as an adult by up to 32%1.

Managing Diabetes

Insulin injections, the first class of biologic drugs to be marketed, are often prescribed to diabetics to control their blood sugar. While type 1 diabetes patients require insulin replacement therapy, type 2 patients are encouraged to manage the disease by controlling their weight and diet. However, they may eventually require insulin injections along with oral medications as the disease progresses.

blood sugar monitoring device
Diabetics must monitor their blood sugar levels at regular intervals

Apart from the inconvenience of managing the disease, both types of diabetes lead to further health complications later in life. Diabetes damages blood vessels, with heart disease responsible for the death of 75% of diabetics2. Vision loss, kidney failure and nerve damage are also implicated in the disease. The WHO ranks diabetes as the #9 global cause of death, killing 1.5 million people in 2019.

The Discovery of Insulin

Banting and Best

Although the link between diabetes and pancreatic dysfunction was established in the early 1900s, it took hundreds of attempts before the molecule responsible for regulating glucose—insulin—was discovered. Working at the University of Toronto in 1921, Canadian scientists Fredrick Banting and Charles Best were the first to obtain working insulin extracts from the pancreas of dogs. Using new (at the time) techniques like Benedict’s test, they were able to show that their extracted insulin worked to regulate blood glucose levels.

Banting and Best proceeded to administer their insulin to diabetic patients and brought them back from the verge of death, immediately garnering worldwide attention. Knowing that their discovery could have far-reaching benefits, they promptly sold the manufacturing rights for insulin to the University of Toronto for just $1 each, in the hope that everyone could soon have access to their drug.

In 1922, pharmaceutical company Eli Lilly took over manufacturing, extracting commercial quantities of insulin from the pancreas of slaughterhouse cows and pigs that went on to save millions of lives. Insulin was single-handedly responsible for Eli Lilly’s early success in the pharmaceutical industry, where it remains a key player today.

banting and best working with insulin
Banting and Best in their laboratory at the University of Toronto in 19213

Other Heroes of Insulin Development

Fredrick Banting tragically died in a plane crash in 1941 at the age of 50. When Charles Best died in 1978, he was interred next to Banting at Mount Pleasant Cemetary in Toronto.

In Banting’s hometown of London, Ontario, a monument named ‘The Flame of Hope’ was erected in 1989. Atop it sits a flame, resistant to wind, rain and snow, waiting to be extinguished by the scientists that discover a cure for diabetes. It serves both to honor Banting’s contributions to the discovery of insulin as well as a reminder that although diabetes can be managed, we must still strive to discover a cure for this deadly disease.

In 1955, British biochemist Frederick Sanger discovered the 51 amino acids that insulin is comprised of, making it the first protein to have its amino acid sequence fully deciphered. Another British chemist, Dorothy Hodgkin, took this a step further and in 1969, she completely elucidated the 3D structure of insulin using X-ray crystallography.

These discoveries enabled the manufacture of insulin at enormous scales in the present day. By modifying the DNA of E. coli bacterial cells, we can create ‘human’ versions of the protein instead of ‘animal’ forms that the body might reject. Using genetic engineering, insulin can even be modified to give it useful properties such as a faster mode of action.



Deadly Costs of Insulin Injections

Although insulin ranks among the greatest medical discoveries in history, cost issues are preventing some patients from receiving these life-saving injections. In the United States, insulin prices tripled between 2012 and 2016, from US$ 2864 to US$ 5705 for a year’s supply4. In fact, the price of insulin in the US has steadily increased since 1991.

To cope with the yearly increase in price, many diabetics are forced to ration—administering lower-than-prescribed doses of insulin. The widely publicized death of Alec Raeshawn Smith due to insulin rationing is just one of many such cases. After he aged off his mother’s insurance plan, his diabetes supplies started to cost US$ 1300 a month. With his yearly salary of US$ 35000, he wasn’t eligible for subsidies and hence he started to ration his insulin supply, with tragic results.

Affordable Except in the US?

You might think that the rising cost of insulin is a worldwide problem. But over the years, insulin has actually become cheaper and cheaper to manufacture. In the developing world, a 10 ml vial of insulin—roughly half a month’s supply—sells for as low as US$ 3.05. It’s the same insulin that is available in the US, so why the price discrepancy?

Pharmaceutical companies price their drugs differently in each country to match the costs of living so that more people will have access to the medication. If they sold insulin in developing countries at U.S. prices, nobody would be able to afford it there. However, to offset the losses of offering low-cost drugs in poorer countries, pharmaceutical companies then try to increase the price of the drug in countries that can afford to pay more.

Governments will often negotiate with pharmaceutical and insurance companies to agree on a suitable price that patients will pay for insulin, known as the out-of-pocket (OOP) cost. However, there is no such system in the U.S.; pharmaceutical companies are given free rein to agree on prices with insurance companies and prescription pharmacies, resulting in the OOP costs for diabetics skyrocketing in recent years.

Rebates, But Not for the Patient

Because there is little government regulation when it comes to pricing, insurance firms and pharmacies incentivize pharmaceuticals to provide ‘rebates’ on drugs. For example, if a vial of insulin sells for $100, pharmaceutical companies might return $70 to the seller. The more they offer in rebates, the better marketing their drug receives. Insurance companies might improve the coverage of drugs with high rebates, while pharmacies might give it better product placement on store shelves.

This system encourages insulin manufacturers to list the drug at absurdly high prices while offering similarly large rebates. But the diabetic patients don’t benefit directly from these rebates. The rebates go directly to insurance companies and pharmacies, while people in need of insulin must still bear its full cost.

If a pharmaceutical company offers cheaper options of a drug without providing rebates, this system works against them. Pharmacies can then choose not to stock sufficient quantities of the drug, making it unavailable to patients. Insurance companies can decide not to provide coverage for the cheaper options in their plans.

In response to public pressure, the primary insulin manufacturers in the US—Eli Lilly, Novo Nordisk and Sanofi—have taken action to address the high OOP costs of insulin. Since 2019, they have offered savings programs that enable diabetics to fill their prescriptions at a fraction of the original retail prices, regardless of insurance and employment status.

Accessible and Affordable Insulin

It is uncertain how long these programs will last, but for the time being, they ensure diabetics won’t have to resort to rationing their prescriptions and risking their lives. Insulin rationing isn’t the only consequence of its high prices, though. More diabetics are buying cheap insulin from shady online pharmacies that sell unregulated, even counterfeit drugs, presenting further health risks.

There are more than a million type 1 diabetics in the US alone, many of whom struggle with the costs of treatment. When Banting and Best discovered insulin, they resolved to make the miracle drug easily accessible and affordable to all. If they were still alive today, they would face the poignant truth that—more than 100 years later—their vision has yet to become reality.



Reference

  1. Huang, H., Yan, P., Shan, Z., Chen, S., Li, M., Luo, C., … & Liu, L. (2015). Adverse childhood experiences and risk of type 2 diabetes: a systematic review and meta-analysis. Metabolism64(11), 1408-1418.
  2. O’Gara, P. T., Kushner, F. G., Ascheim, D. D., Casey, D. E., Chung, M. K., De Lemos, J. A., … & Granger, C. B. (2013). 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Journal of the American college of cardiology61(4), e78-e140.
  3. Li, J. J. (2006). Laughing gas, Viagra, and Lipitor: The human stories behind the drugs we use. Oxford University Press.
  4. Biniek, J. F., & Johnson, W. (2019). Spending on Individuals with Type 1 Diabetes and the Role of Rapidly Increasing Insulin Prices. Health Care Cost Institute.

About the Author

sean author
Sean Lim

Sean is a consultant for clients in the pharmaceutical industry and is a lecturer at a local university, where unfortunate undergrads are subject to his ramblings on chemistry and pharmacology.

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