Diabetes, Inc.

Colleen Fuller, a health policy researcher in Vancouver, British Columbia, has been living with Type 1 diabetes for over fifty years. In the 1990s, she was one of the thousands who nearly died after transitioning from animal insulin to recombinant “human” insulin. This traumatic experience prompted her to form an organization to protect access to animal insulins. The Society for Diabetic Rights attempted to bring a class action against manufacturers Eli Lilly and Novo Nordisk in response to widespread harms suffered and succeeded in convincing the Canadian government to identify animal insulin as an essential medicine. Here, she engages with Diabetes, Inc. co-author Audrey Farley on the lasting impact of biosynthetic insulin’s introduction and lessons for patient advocates today.

AF:  In the 1990s, after nearly dying from using biosynthetic “human” insulin, you formed the Society for Diabetic Rights, which fought to preserve Canadians’ access to animal insulins, among other initiatives. Can you say more about this group? 

CF: SDR was co-founded by Katharine Ferguson and me. Kathy’s 17-year old son, Chris, had died during the night, a classic “dead-in-bed” incident. She and I originally set out to sue Eli Lilly and Novo Nordisk, as well as the Government of Canada, for the harms associated with rDNA human insulin. We were fuelled by grief and anger at the beginning and that hasn’t subsided to this day. I don’t think we had any clear strategy about how to raise the alarm, but we knew a lot of other people were struggling with that insulin. I have a background in health care and communications – so I knew we had to connect with the media. I contacted Erica Johnson, the producer of a popular CBC-TV program called Marketplace, which focused on consumer issues. Erica interviewed Kathy and me, Arthur Teuscher, Health Canada, the CDA, and other diabetics and the show went on air. 

The response to the program was overwhelming. The CBC said Marketplace had never received as many letters and comments as it did for that show. Kathy and I were bombarded with letters, phone calls, email messages so we knew we were going to have a voice in Canada. And by “voice” I don’t mean just her and me, but the large number of people who were also confused and angry. 

That’s how SDR got started. We then developed a kind of systematic approach: we encouraged each and every person who contacted us to report the harm they had experienced to Health Canada; we fundraised so we could get a legal opinion on a class action lawsuit against the two companies (we dropped Health Canada); we began petitioning Members of Parliament to raise the question about animal insulin and the safety of “human” insulin in the House of Commons; we began lobbying for a national enquiry and subsequently for a national insulin strategy. The latter was a demand because the industry was now in the driver’s seat, but we believed Health Canada should be driving the car. And we pushed Health Canada to notify doctors and the public that animal insulin was still available in Canada. This was important because all of us had been told it was no longer available – by our doctors, pharmacists, everyone. Some of the harm we had experienced could have been avoided if we had known that Eli Lilly, unlike Novo Nordisk, was still supplying modest amounts of pork insulin.

We were treated with contempt by both companies who denied that the problems we reported were linked to the insulins they made. That attitude was reflected in the medical profession, in particular the endocrinology community which seemed to be on the corporate payroll. We discovered that most doctors believed there was no animal insulin left anywhere in the world and that it had been withdrawn because it was a bad drug. SDR members reported to us that when they told their specialists they wanted to be put back on animal insulin, the specialists threatened to “fire” them as patients. Some of the doctors suggested our members seek psychiatric help (this also happened to me). General practitioners were much better, but by this time they had less and less involvement in (co)managing patients’ diabetes who they automatically referred to an endocrinologist. 

In retrospect, SDR was amazingly effective. We succeeded in getting a two-day hearing by the Parliamentary Standing Committee on Health (acronym: HESA) which recommended that Health Canada initiate discussions with the FDA for a North American insulin strategy. (The FDA said no.) They also recommended that Health Canada take immediate steps to assure diabetics who wanted/needed to access animal insulin were able to do so in a cost-effective manner. Health Canada worked closely with us to develop communications bulletins, etc., alerting the public and doctors to the fact that animal insulin was safe and available and that certain patients could not safely use recombinant human insulin. Today, most doctors are aware that pork insulin is available in Canada, even though they are unlikely to initiate the discussion about it with patients struggling on “human” or analogue insulins. 

We also forced Health Canada to review reported harms. Although they publicly insisted there was nothing unusual going on, we know that they heard our voices. Initially, when Marketplace was broadcast, HC had denied there were reports of serious harm but we had obtained all of the reports to that time of adverse reactions linked to both human and animal insulins and the difference in numbers was pretty amazing.  The ADR database, like those in all other countries, reflect only 1-5% of actual experience, so I think they had to back off from the claim that everything was good in Kansas (so to speak). 

SDR became an expert on insulin, which was important. We read every study on insulin that had been published between 1956 (when the Lente series of insulins were introduced) and the present. We didn’t understand all of it, but we had a pretty good picture of what was going on. We connected with diabetics, scientists, and physicians around the world who were fighting the same battle as we were. We definitely raised public awareness in Canada about the issue and our membership grew to over 300 people across the country. 

Because of our work, Canada was the first country to acknowledge that animal insulin was an essential medicine because not everyone could safety or effectively use recombinant human insulin. Along with Switzerland, Canada asked the WHO to list animal insulin on the Essential Medicines List (they declined). Health Canada, in 2008, established an Expert Advisory Panel to help it further develop a policy approach to the issue and the top scientist (Agnes Klein) in the Biologics directorate published a paper through the Public Health Agency of Canada on the role of animal insulin in diabetes therapy. 

I think we also continue to see our work reflected in how some endocrinologists now view insulin therapy today. This is purely anecdotal, but it seems that doctors are aware of the inadequate tools diabetics have to safely and effectively manage their condition. Manufacturers are more often criticized than they were before because the range of insulin options that people need just isn’t there. 

AF: Do you believe the mission of SDR is still critical today? If so, why?

CF: Yes, I definitely do. Most people today know nothing about the work we did, and also know nothing or very little about animal insulins and why they are so essential. Our struggle underscored the fact that people with diabetes need a much broader range of options within the insulin “family.” 

The demand for a National Insulin Strategy is still legitimate and in fact has become even more urgent. I think SDR laid some of the groundwork for such a demand – we’ll see whether others now active in this area pick up on that. This means that many people continue to suffer because they’re using the wrong insulin. So a national strategy must include efforts to raise public and physician awareness that not all diabetics are the same – and in fact, not all Type 1 diabetes is the same disease or has the same profile. A national strategy also should tap into our own history in Canada of public manufacturing of insulin. Domestic manufacturing poses some challenges in this era of biotechnology, but we should at least explore our options. 

The activists today could also learn from our experience with government. SDR developed a lot of productive relationships with Health Canada and the Standing Committee on Health. Other organizations could benefit from that. 

AF: The number of individuals using animal-sourced insulins is dwindling. Why is it so important to preserve access? 

CF: Animal insulin is a safer type of insulin than other options. Its action profile is better, and it lasts longer. More importantly, perhaps, some people have life-threatening experiences with recombinant and analogue insulins. The reasons aren’t clearly understood, but regulators – not including the FDA – recognize that some people have a type of diabetes that causes an overall immune response. Also, some people are unable to detect early warning signals of hypoclycaemia, which can also be life-threatening. 

People need as many insulin options as possible, backed up by evidence of safety and effectiveness and on-going diabetes education to support their ability to make informed decisions about insulin therapy. 

AF: Do you see parallels between the SDR and other activist groups within the diabetes community? And if so, what insights would you offer to these activists? What lessons could they learn from the challenges faced by groups like SDR in the ‘90s and early 2000s?  

CF: SDR members were fighting for access and affordability – two issues that link our struggle with people campaigning today. We were fighting for access to a different type of insulin, but the basic issue – life or death – is no different. We are all vulnerable precisely because the three big companies, Eli Lilly, Novo Nordisk and Sanofi, have our lives in their hands. They don’t base their decisions on our lives, but on their bottom line.

History is very important and calling up the memories of Banting, Best, etc., is good, we have a lot to learn from those less profit-driven times. But skipping over the important fight against the withdrawal of animal insulin, which was an international campaign beginning in the late 1980s, will handicap the current struggle for access and affordability. When SDR got started, we were completely unaware of the fact that a small group in Alberta had been fighting for beef insulin to remain on the market when Lilly pulled it in 1998. When we found out, we learned that they had made a kind of fatal decision to align themselves with the Canadian Diabetes Association, which was pretty much the same thing as jumping into bed with Pharma. They lost access to beef insulin when it disappeared. 

Another important lesson is that when people conclude they’ve won the battle, they pack up and go home. They also pack up and go home if they believe they’ve lost. This is what manufacturers count on, as far as I can tell. They are patient people and take the long view of things; they have five-year and ten-year corporate plans while we have plans to get what we need and get it now. 

We have to build a plan for the long term. The Insulin Dependent Diabetes Trust is the only group left that was fighting for animal insulin, and the organization continues to be a leader in the discussion about health policies in the UK that determine access not only to animal insulin, but all insulins. The IDDT is an important, independent, and critical voice of the industry as well. It built a membership base, steered clear of Pharma funding, established enormous credibility in Britain on insulin- and diabetes-related issues. The organization hasn’t been as successful on the international stage, but because of the work it did, there is one manufacturer on this planet that continues to supply animal insulin in the UK as well as in Canada and possibly other countries. IDDT also campaigned very strongly on the issue of informed choice, something that no other group has done or is doing. 

Another important lesson is this: make sure you always know the evidence and can address the situation from that perspective. If the evidence is weak or skewed, know that, too. The campaign for access to lower-cost analogues is swimming against the best available evidence on safety and effectiveness and by that I mean studies that are not funded by industry. If you read that evidence, the best that can be said about analogues is that they’re no different in terms of the endpoints used in almost each and every study: the incidence and severity of hypoglycaemia and HbA1c. But the price is very much higher than first-run rDNA human insulin. HbA1c is a surrogate marker whose utility is unclear, while hypoglycaemia is definitely a quality of life issue. The endpoints that are important to patients include quality of life, mortality, and diabetes-related complications, which are rarely if ever studied. 

The arguments against so-called “Walmart insulin” are weak in my view and contain a kind of judgement about the quality of older drugs (and, by implication, of the people who use them) which is unfortunate. Humulin insulin is bad, not because it is an “old” drug but because it’s a bad drug and was from the moment it came on to the market. The industry and its flunkies in the medical profession disparaged animal insulin because it was old and outdated. I hear echoes of this in the campaign around analogues.  These views align very well with the interests of the industry, which has long planned to withdraw these rDNA human insulin products to force people to use much more expensive analogues. So, although manufacturers are on the defensive (and should be) as far as price goes, they are probably okay with the line that rDNA human insulin is an old drug and therefore should give way to more modern analogues. And they will win the argument that better justifies a high price tag. In fact, they have won that argument so far – analogues all over the world are more costly than first-run “human” insulins, even in countries with price controls. 

AF: Scholars, medical providers, drug makers, and investors have hailed biosynthetic insulin for modernizing Banting’s “crude” diabetes treatment (animal insulins). One journalist compared biosynthetic insulin to the space shuttle superseding Charles Lindbergh’s plane. You don’t find this narrative very compelling. Why not?

CF: There is no evidence to suggest that biosynthetic insulin was an improvement over animal insulin. Despite that it’s cheap to make, it was much more expensive than animal insulins, which many people need to have any kind of decent life. If manufacturers wanted to introduce another portfolio of insulins that would have been great – it was estimated in the early 1980s that between 1 and 3 per cent of people had allergies to animal insulin. Even though that population is very small, they have as much right as anyone else to a type of insulin that is safe and effective for them to use. But that was never the idea. 

AF: You’ve suggested that the introduction of biosynthetic insulin changed the global insulin landscape for the worse, reducing access to lifesaving treatment in poor countries. Can you elaborate on this? 

CF: This is a theory, not a conclusion! Biotechnology is an expensive method to produce what was a very cost-effective drug. Access and affordability have always been issues so this isn’t anything new. But my view is that those two issues depend on national laws and regulations since there is no international regime that guarantees that people or governments will be able to obtain insulin at a reasonable cost. Today, governments act as if they’re all in the same chorus, singing the same lines: we can’t force a company to introduce a product even if it’s desperately needed; we can’t force a company to maintain a product on the market; we can’t force a company to manufacture within our country; and we can’t make it ourselves. 

Even if countries decided to make insulin domestically, they would have to deal with the significant investment that’s needed to support the use of this particular technology, which is designed for mass production. Aiming to supply smaller populations might be very problematic and not at all cost-effective. In Canada, for example, there are roughly 2.3 million people diagnosed with diabetes. Of these, about 300,000 have Type 1 diabetes, and an estimated 40% of those with Type 2 diabetes use insulin. That’s an insulin market of about 1.1 million people. When Novo Nordisk pulled all of its animal insulin products from the Canadian market, there were over 45,000 people who relied on the approximately 26-28 different types of animal insulin that was available at the time. Biotechnology isn’t designed to supply what manufacturers would term a fragmented market, and they have gone to great lengths to eliminate variations in the supply of insulin. The worldwide market for insulin now is about 100 million people, three different companies compete for dominance with five types of insulin, excluding animal insulin. 

It’s true that Eli Lilly and Novo Nordisk claimed that biotechnology would save diabetics from a predicted shortage of pancreatic glands. This was pretty much pure propaganda as documents in the U.S. have shown. Instead, manufacturers have put insulin out of reach of millions of people in low- and middle-income countries, in particular, but in the United States as well – a very rich market by comparison. Half of all people who require insulin now cannot get it, either because it isn’t supplied in their countries or because they can’t afford it. 

My theory also is that animal insulin better suits domestic manufacturing for national markets. But countries need support to establish domestic production, and that isn’t there. The WHO offered to give biosimilars their stamp of approval instead of assisting countries to become insulin self-sufficient. This strategy will strengthen the role of three global manufacturers in supplying insulin, rather than working with countries to establish domestic production over which they would have legal control, especially (and preferably) if it was done in the public sector. They also have no interest in addressing the important issue of diverse supply and use of local resources where possible, i.e., cows, pigs, sheep, fish, etc. The WHO are aiming to support reliance on technology that was specifically designed for large global - not domestic - markets, thereby re-enforcing the dominance of global producers.  

AF: Other than costing more money, leading to shortages and rationing in low- and high-income countries alike, how have biosynthetic insulins transformed the experience of living with diabetes? 

CF: There are a number of factors that have had an impact on people who use insulin, especially those with Type 1 diabetes. These are inter-connected in ways that deserve to be studied, including the type of insulin being produced, the emergence of global alliances between insulin and device producers, the boom in the production of high-cost monitoring devices – or rather, the test strips not the devices which are free in Canada – as well as the overall impact on emergency and hospital services. Type 1 diabetes has always been a challenging disease to manage, which is why we need to have the very best tools. The types of insulin produced using biotechnology are known to have a much sharper action profile than their animal predecessors, are often less predictable and less stable, and have contributed to significant increase in the incidence of hypoglycaemia unawareness. All of this has changed the experience of people who use insulin. We test more and rely more on external technological inputs, including delivery vehicles like insulin pumps, continuous glucose monitoring, alarms for parents who struggle to avoid nighttime hypoglycaemia in their children, and so on. These are very modern experiences and I’m not arguing that things were easy before, but I do think things were a lot easier. The use of some of this technology is meant to counter the lack of stability and predictability in the recombinant and analogue insulins that are now available, some of it combined with hypoglycaemia unawareness, a deadly mix. 

The other group that has been significantly impacted – and in some ways even more than Type 1s – are people with Type 2 diabetes. Biotechnology is about big and expanding markets, not just geographically but on a population basis as well. The marketing of insulin to treat Type 2 diabetes is controversial and many experts (e.g. Yudkin) argue that insulin therapy for this group is almost always inappropriate and contributes to poor health outcomes. Type 2 diabetics far outnumber Type 1s, and are therefore a greater priority for manufacturers, so the marketing of insulin as a first-line therapy has been extremely aggressive. 

AF: You’ve argued elsewhere that you don’t believe any species of insulin should be removed from the market, even if it has caused widespread harm. What is your rationale for this? 

If I gave that impression I apologize – am I quoted somewhere saying that? I don’t believe it at all. Deep down in my heart I think that the NPH recombinant human insulin is the worst insulin ever produced and should probably be pulled from the market. Inhaled insulin is another bad idea and should never be introduced. Exubera was pulled by Pfizer, which said it had taken these steps because sales were low. But its approval by the FDA was controversial because of its safety profile. I also wonder if insulin glargine (Lantus) should remain on the market because of studies suggesting a positive link to cancer. 

What I do believe is that insulin from different species would support a more diverse market and countries/regulators should be focused on that issue. 

AF: If you could dispel one myth about the history of insulin or about individuals living with diabetes, what would it be?

I would want to dispel any ideas that Eli Lilly was even remotely involved in the great discovery in 1921. I would want to resurrect the role of Canada’s public sector in this important discovery as well as its affordability and worldwide distribution. No private corporation has ever matched that accomplishment – in fact, it’s been the opposite. 

I would want to dispel the myth that animal insulin was or is an inferior type of insulin or that it was withdrawn for safety reasons. It was withdrawn because manufacturers were greedy and wanted to eliminate a better and more affordable alternative. 

AF: Why do you want to write Diabetes, Inc.? Why is this book important to you?  

CF: I want the truth to be told and to honour those who have been on the front lines of fighting for fairness and even justice for people who have this complicated disease. I want there to be the truth of what we’re living with now and I hope the book will inspire people to make a better story. 

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