Updated: Dec 14, 2021
Part 4 of Access to hope: The discovery of insulin 100 years on
Bec Johnson, Type 1 Diabetes Family Centre CEO
November 14, 2021
“[The] initial positive views on the prospects of insulin therapy in the 1920s are in harsh contrast to the reality that many people with diabetes face some 100 years later, specifically owing to lack of access to insulin.” – David Beran
When insulin was first discovered, the research team that discovered it was clear in its commitment to make no profit from its discovery. Sir Frederick Banting reportedly declared that “Insulin does not belong to me, it belongs to the world.” Instead, the team handed the patent for insulin over to the University of Toronto for one US dollar. Pharmaceutical companies and investors immediately began to circle, but the team was resolute. Banting recounted a bizarre encounter with one visitor in 1922: after casting his eyes about Banting’s modest rooms, the man declared “Well you are a dammed fool!” and attempted to persuade Banting to hand over the patents to insulin to a group on Wall Street, for which he would be given $1,000,000 in cash and “all the laboratories [he] desired”. The group intended to patent insulin all over the world and create a chain of diabetes clinics through which to sell the insulin. Banting said “To me … it was not even a temptation. It meant the suffering of the diabetic would be exploited.” Banting refused the offer.
Fast forward a century, and despite the noble intentions of those who discovered it, insulin is the sixth-most expensive liquid in the world. Three companies - Eli Lilly, Sanofi, and Novo Nordisk – hold more than 99% of the total insulin market by value, 96% by total market volume, and 88% of global product registrations. The University of Toronto’s Board of Governors’ decision to collaborate with Indianapolis pharmaceutical company Eli Lilly in 1922 to produce insulin at scale was made with good reason and caveats; the Board stated that although its decision would place Eli Lilly at an advantage over its competitors, “[the competitive advantage] is much less serious than … further delay in proceeding intensively with production on a large scale.” It committed to give firms and hospitals “every chance to do the best they can by publishing the details of the method as at present used [to extract and purify insulin].”
They were right about the competitive advantage, however. After its head start, insulin – originally marketed as ‘Iletin’ - quickly became a blockbuster product for Eli Lilly. By 1923, insulin was the highest-selling product in Eli Lilly’s history, accounting for over half the company’s revenue. Novo Nordisk and Hoechst (now Sanofi) started production in 1923 and the battle for dominance over the insulin market began.
One of the most significant breakthroughs in the insulin market occurred nearly sixty years later, when Eli Lilly launched its genetically engineered biosynthetic ‘human’ insulin in 1978, selling it commercially in 1982 under the brand name Humulin. Humulin was not made from animals, rather it was grown using E. coli bacteria in a laboratory. A new class of insulins was born in the 1990s – ‘analogue’ insulins, which were genetically altered to create insulins that worked faster, or slower, than basic human insulin, giving people with diabetes more flexibility. Analogue insulins, which were more expensive to purchase than human insulins, were increasingly prescribed. Animal insulins disappeared.
Analogue insulins now dominate a market that is predicted to reach $27.7 billion USD by 2026. In 2020, NovoNordisk posted 56.5 billion Danish kroner ($8.7 billion USD), Eli Lilly $5.8 billion USD and Sanofi 3.6 billion Euro ($4.1 billion USD) in insulin sales. One of the reasons for these eye-watering revenues is that insulin prices have soared over the past few decades. In the USA, for example, list prices for insulin rose 262% over the decade between 2008 and 2018 - Humalog’s cost per vial jumped from $21 in 1999 to $332 in 2019, nearly a 16-fold increase. Spending on insulin by people with type 1 in the USA nearly doubled from 2012 to 2016 from $2,900 to $5,700, primarily driven by price increases.
The Australian government subsidises insulin for people with diabetes; a prescription priced at more than $350 costs a patient only $41. Without this crucial subsidy, which costs taxpayers millions, many Australians would not be able to afford insulin. For many people in low- and middle-income countries and low-income populations in the USA this is the reality; insulin is out of reach. One in four people in the USA ration insulin, and many have died as a result. Academic and researcher David Beran PhD writes: “On a global level the main cause of mortality for a child with type 1 diabetes is a lack of access to insulin, and in sub-Saharan Africa the life expectancy of a child with type 1 diabetes can be as low as 1 year.”
Beran has written doggedly about the issue of insulin access for nearly 20 years. In a paper from 2018 he and his co-authors argue that each actor – governments, private companies, and NGOs – has a critical set of responsibilities that influence the accessibility and affordability of insulin. As an example, he writes that governments should legislate to prevent monopolies, fund research to bring novel, cost-effective products into existence such as biosimilar (essentially generic) insulins, and reduce the onerous regulatory burdens around bringing such products to market. He reminds pharmaceutical companies that in providing products that keep people alive they have a special responsibility over and above their responsibility to generate profits for shareholders.
Advocacy group T1 International calls it more plainly. In its 2018 paper 8 reasons why insulin is so expensive, the group slams insulin companies for pay-for-delay schemes and lawsuits (paying competitors to prevent cheaper insulins from coming to market), patent evergreening (taking advantage of loopholes in intellectual property laws to create thickets of patents around their products), price fixing (increasing prices in lockstep with other companies to prevent competition), intense political lobbying, and buying brand loyalty from prescribing physicians through gifts and incentives.
T1 International and Beran both examine the role of ‘the plural sector’ – NGOs and civil society, whose role it is to “redress imbalances and challenge the status quo.” To be able to do this, writes Beran, the sector “needs to be free from influence of governments and the private sector” – in short, “owned by no-one.”
And yet, the major diabetes associations all list insulin companies as corporate partners. Eli Lilly, Sanofi and Novo Nordisk are corporate partners of both the American Diabetes Association (ADA) and Diabetes UK, and hand over millions through these arrangements – cumulatively $53.6 million in the case of ADA’s Pathway Sponsors. Eli Lilly and Sanofi are corporate partners of Diabetes Australia. Eli Lilly, Sanofi and Novo Nordisk are all also corporate partners of the International Diabetes Federation (IDF) and on the Corporate Liaison Board of the Endocrine Society.
To date, not one of these organisations has made effective inroads into the issue of access to insulin. The ADA and IDF have made statements and released reports, but they fail to go to the heart of the issue – the prices pharmaceutical companies set for insulin. T1 International calls this “payment for silence.”
On pricing, the IDF’s 2016 report recommends four initiatives, including improving supply chain distribution, promoting competition through biosimilars, and improving procurement practices. Its one actual recommendation about pricing – to introduce “equity pricing” i.e. differential pricing tiers for low- and high- income countries - it quickly doubles back on, stating “there are concerns differential pricing will result in product diversion, with cheaper drugs leaking back into wealthier countries.” The report, which also looked at drugs for people with type 2 diabetes, was funded by Novo Nordisk and Astra Zeneca.
The ADA’s white paper on insulin access and affordability called for transparency in the complex insulin supply chain in the USA, where markups occur at multiple points. Nonetheless, it writes that “manufacturers set the list price for each insulin product” and the list price is where the problem lies. Despite this, not a single one of the report’s twelve recommendations directly confronts insulin pricing by pharmaceutical companies, by proposing, for example, that lawmakers take action to regulate pricing. The closest the ADA gets is a recommendation that it should itself “advocate for access to affordable and evidence-based insulin preparations for all people with diabetes” – a recommendation that is nestled as a sub-point at the very bottom of the report.
Dr William Cefalu, Chief Scientific Officer and first author on the ADA’s white paper, presented at a Congressional Hearing on insulin affordability in 2018; not once did he state that pharmaceutical companies were the problem. Despite 432,000 signatures on a grassroots petition campaign about insulin affordability, the ADA has failed to achieve real, national action on insulin pricing in the USA. In the absence of federal insulin pricing regulation, some states have themselves taken on the issue of insulin affordability. While some inroads have been made to cap the co-payment amounts for people with diabetes, list prices remain excessive, and the result is a patchwork of rules that do not apply to many, including the most vulnerable: people on Medicaid and those who are uninsured.
The Endocrine Society, an international medical organisation in the field of endocrinology and metabolism, waited until 2021 to issue its statement about insulin affordability. Rather than recommending price reductions, its two suggestions for insulin manufacturers include “improv[ing] patient assistance programs” (programs run by pharmaceutical companies that offer lower priced insulin to some under strict eligibility criteria, ensuring prices for most stay high, described in one US Congressional Hearing as “a bandaid”) and “eliminat[ing] co-pay savings cards”. Echoing the ADA’s white paper, the Endocrine Society also recommends “training healthcare providers to use lower-cost human insulins”: both the ADA and the Endocrine Society point patients towards the inferior insulins of the 1980s, rather than calling for price reductions on analogue insulins.
Insulin access is not an issue for Australians, and we have our Pharmaceutical Benefits Scheme and our fellow taxpayers to thank for that. However, it is unacceptable that around the world, many people with diabetes in 2021 are unable to access a discovery from 1921. The Australian diabetes community must know about this problem. Those for whom this injustice compels action should support the work of independent advocacy groups like T1 International. They can also demand the associations that purport to represent people with diabetes untangle themselves from their insulin company partnerships and do the hard, courageous work required to get to the heart of the issue: true, systemic solutions to insulin access for all.
Conclusion: Access to hope
“Better treatment of diabetes should be universal … The means are at our door.”
- Elliott P. Joslin
The evolution of diabetes care since the discovery of insulin has been one of milestones and mistakes: great leaps, disruptive innovations, ethical failures and stunning injustices. The issues of access – to devices, to quality information, to community and to insulin itself – may take different forms, but they are just as compelling today as they were 100 years ago. We must push forward into the coming century with a common goal: to ensure equity of access for people with diabetes. Though we face a challenging road ahead, we must always bear in mind the miracle of insulin and the spirit of hope that led to its discovery. For the past century, insulin has allowed millions of people diagnosed with diabetes to live up to their potential; Elliot Joslin wrote this of its remarkable impact in 1924: “With the help of insulin I have seen children go back to school, ministers secure a parish, lawyers re-enter court, doctors carry on a hospital services, [and] a nurse resume work.” And therefore, as we strive for universal access to the devices, information, community and medicine people need to thrive with diabetes, we honour the achievements of Banting, Best, Collip, and Macleod and the extraordinary gift they gave to the type 1 community in 1921: the gift of life.
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