Health emergency in slow motion

We are facing a global pandemic of diabetes made worse by the unnecessary lack of insulin
October 19, 2011
Above: an insulin factory in Russia


There is a global diabetes pandemic. The disease already kills an estimated 3.2m people every year worldwide—more than Aids—and the numbers are set to rise dramatically. According to the International Diabetes Federation (IDF), 285m adults had diabetes in 2010; by 2030, this will be 438m, or 7.8 per cent of the adult population. Diabetes comes in two varieties: type 1, which is congenital; and type 2, which can be brought on by factors such as lifestyle. According to the IDF: "type 2 diabetes constitutes about 85 to 95 per cent of all diabetes in high-income countries and may account for an even higher percentage in low and middle income countries." Type 1 is predominant amongst the young in developed economies.

In 2009 Ban Ki-Moon, secretary-general of the UN, warned that the disease no longer only affects the wealthy, but hampers “the people and the economies of the poorest populations, even more than infectious diseases.” He said it was “a public health emergency in slow motion.” At a recent UN high-level meeting called to discuss the global spread of non-communicable diseases, which include both types of diabetes, Nassir Abdulaziz Al-Nasser, the UN general assembly president, said: “The public health pendulum has swung too far, focusing too much on a few diseases, while denying attention and help to those who suffered and died from less dramatic but no less fatal diseases.”

As the incidence of diabetes rises, more insulin is needed to combat it. But the west overpays for much of its supplies, while millions in developing nations get none at all. That will place huge burdens on health services in both rich and poor countries. The strain has already reignited rows about how insulin is made and sold.

Diabetes mellitus is a disorder of the metabolism that causes blood sugar levels to rise. Small islet cells in the pancreas normally produce a hormone that regulates sugar levels, but in diabetics these islets do not function. Blood sugar rises and, without treatment, the patient will die.

There are ways of avoiding type 2 diabetes. Diet is crucial: people who eat healthily are less likely to succumb, and those showing early signs can fend off the disease by changing their eating habits. Exercise can have a similar preventative effect and, in the early stages of the disease, oral anti-diabetic pills can stop its onset. But if all of this fails, insulin is needed—and once on insulin, diabetics cannot come off it.

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Gaps in the global distribution of insulin are all the more frustrating because it is an old and well-understood drug—2011 marks its 90th birthday. It was first synthesised in 1921 by Frederick Banting, a surgeon from Toronto, along with his assistant, Charles Best. The two conducted experiments drawing on the work of two 19th-century German scientists, Minkowski and Von Mering, who had established that when a dog’s pancreas was removed, it developed diabetes. Banting and Best removed the pancreases of healthy, non-diabetic animals, and broke them down using chemicals to create a drug, which they injected into diabetic dogs. On receiving the drug, the blood sugar levels of the dogs fell.

In early 1922 the new drug, initially named “Isletin,” was tested on its first human subject, a 14-year-old boy in a Toronto hospital. The first attempt ran into complications, but a second, cleaner dose was administered. The effects were almost instantaneous, the recovery complete and startling. They next took their drug around the hospital to treat other patients, injecting wards of comatose children who awoke, to the delight of waiting family members. Banting and Best had done it. A disease that throughout history had set sufferers on a slow descent into coma and death had been neutralised. The Canadian historian and academic Michael Bliss captured something of the drug’s miraculous qualities in his 1982 book The Discovery of Insulin: “Those who watched the first starved, sometimes comatose, diabetics receive insulin and return to life saw one of the genuine miracles of modern medicine. They were present at the closest approach to the resurrection of the body that our secular society can achieve, and at the discovery of what has become the elixir of life for millions of human beings around the world.”

However, insulin does not cure either type of diabetes: it only staves them off. Diabetics require a steady supply of the drug—without it, blood sugar levels begin to rise and the illness reasserts itself. Untreated diabetes brings with it a host of health risks, including strokes, heart disease and loss of feeling in bodily extremities, which can lead to amputations, and even blindness.

Banting and Best’s work was rigorous, hard science—but what they showed was that once the process is understood, insulin is easy to manufacture. The story of Eva and Victor Saxl shows quite how easy. The Saxls were a Czechoslovakian Jewish couple who fled the Nazis by boat to Shanghai in 1940. But then the Japanese invaded and the occupying army shut all of Shanghai’s pharmacies. For Eva, a diabetic, this was a potentially lethal turn of events. Victor, a textile engineer with scientific interests, borrowed a book on Banting’s method and set about making insulin. He collected pig pancreases from slaughterhouses, processed them into injectable form and he tested the resulting substance on rabbits. When he had done all he could, he injected Eva with what turned out to be a highly effective insulin. His work saved not only his wife, but 400 other Shanghai diabetics.

Until recently, this animal method of production was the standard procedure—so recent that, during the 1982 Falklands war, there was concern that the decline in the import of Argentinian beef pancreases might affect British insulin supplies. But this simple “animal insulin” method was supplanted in the late 1980s by a new production process, and insulin is now manufactured using genetic manipulation of the bacterium Escherichia coli (or E coli). The end product is known as “human insulin.”

Drug companies were involved in the production of insulin from the start. However, they faced a commercial problem: the patent for insulin had been given away by Banting and Best, so their products were not protected. For this reason, they developed patent-worthy variants of human insulin, known as “analogue insulin.” These represent the most sophisticated and expensive end of the market, and their makers claim they are simply better than older variants. They are designed to be faster-acting and longer-lasting than conventional insulin, and the fact that most are injected using a pen-type implement—rather than a syringe—makes them more convenient. However, critics claim they are unnecessary; that the old stuff is good enough, that the pens are gimmicks; and that the cartridges needed to fit the pens cost more than the old vials of liquid.

The International Diabetes Federation estimates that the total global spend on diabetes in 2010 was $418bn (an amount expressed in international dollars, so corrected for purchasing power). A small band of companies dominates the market. These include Sanofi-aventis, Eli Lilly and chief among them Novo Nordisk, a Danish pharmaceutical company specialising in insulin, which in 2010 had total sales of €8.2bn. Novo employs over 30,000 people and, according to its website, enjoys a 51 per cent share in the global insulin production market. Because pharmaceutical production is so capital intensive, newcomers cannot easily break into the industry and market dominance allows companies to upgrade products when it suits them, rather than their customers. This has fuelled the row about whether the drug companies are making “too much” profit from the drug.

“Big Pharma” is a familiar villain: popular fiction and film often cast big drug companies as exploiters of the third world, cruelly squeezing money from those who cannot afford it. Many firms that make the latest insulin products have been strongly criticised for their marketing of the drugs.

Critics point out that, when marketing their products in developing nations, large drug companies will often encourage health services to buy more expensive strains of insulin than they need. So whereas cheap human insulin will do, the marketing of alternative “analogue” varieties is so pervasive that these are bought instead. The difference in price can be great—analogue insulin can cost up to three times as much as human. The decision to opt for the analogue insulin is due not only to the marketing strategies of the companies, but also because the doctors who treat patients are separate from the bodies that purchase the drugs, which generates a mismatch between what is needed and what is supplied. The companies are open to charges of unethical practice when they encourage countries to use up limited funds on expensive types of insulin.

The major drug companies recognise that there is a coming pandemic. But their position is that the crisis has nothing to do with expensive drugs: it is to do with cheap drugs that are widely available already, but ineffectively distributed. Lars Rebien Sørensen is president and chief executive of Novo Nordisk. He points out that pharmaceutical companies have to make money to survive and that they will always try to sell the best products to people who need them. However, when I recently met him in London, he did concede that, “The pharmaceutical industry’s reputation in the developed world is not at the level it ought to be—it is self-inflicted in many ways. So the public view of the industry is not very good—unless you’re dealing with the individuals who’ve benefited from the innovations we’ve brought about.”

Sørensen points out, however, that while developing countries often pay a lot for insulin, the manufacturers are not to blame. In Mozambique, for example, the treatment for one diabetes sufferer takes up 75 per cent of the average wage. In Mali, the figure is 61 per cent and Vietnam, 51 per cent. But Sørensen says that insulin is not only priced by the drug companies. “We are selling insulin in low and middle income countries,” he says. “The average cost per treatment is 15 US cents. Through a pricing study at the receiving end—that is, from the patient point of view—we found the price is being tripled at the point of delivery. It can be marked up five, even ten times. This is due to local duties and tax and is a major issue to deal with. We and the World Health Organisation agree on this.” A WHO spokesman confirmed this, blaming the problem of access on “cost, procurement and supply chain impediments. This is an existing challenge as well as likely to be a future one.”

In recognition of this financial burden, several drug companies now offer their insulin products to developing countries at reduced rates. Novo Nordisk, for example, sells drugs to health services in the poorest nations at 20 per cent of the price paid in the west. This has exerted a downward pressure on prices. A 2006 paper by David Beran and John Yudkin, published in the Lancet, found that the price of insulin in Mozambique had been cut in half by the drug companies’ re-pricing policy. But there has not been the broad flattening effect on the price of insulin that might have been expected. In May 2010, Health Action International, a Dutch NGO, arranged for volunteers in 60 countries worldwide to go to their local pharmacy and buy a single 10ml of human insulin. The experiment found that the prices paid varied by 2,900 per cent. A recent article in the British Medical Journal blamed “profit-taking by pharmacies and other in-country suppliers, rather than… factory price” for the discrepancy in these prices.

Where developing countries are forced to pay high prices, it has a serious economic effect. The WHO estimates that India and China will have $900bn knocked off their economic output between 2005 and 2015 by diabetes and cardiovascular disease. The WHO also found that since 1980, the global obesity rate, a contributing factor to overall levels of diabetes, has more than doubled; in 2008, 1.5bn adults were overweight.

The extent of the threat posed by type 1 and type 2 diabetes does not seem to have been grasped by politicians in developing nations, where health services lack the flexibility needed to address it. As Ban Ki-Moon noted in his 2009 comments, health service infrastructure tends to be arranged to deal with acute conditions, rather than chronic ones. Priorities include hygiene, infection, malaria, water-borne diseases and HIV/Aids. Between 2000 and 2005, the World Bank loaned $4.25bn for health. Of this total, the 2006 Lancet paper found, only “about 2.5 per cent… was allocated to prevention and control programmes for non-communicable diseases, all in eastern Europe.”

But now the disease has reached the attention of international bodies, will there be progress? High-level UN meetings, such as the one held in September, may involve political theatre, but show that diabetes now commands global attention. The UN has discussed health matters at this level only once before: a decade ago, when it convened a session to discuss Aids. The UN holds the purse strings of both the World Bank and WHO, so there is a chance that more money will be allocated for work on non-communicable diseases in future. But there is a lingering view in the developing world that type 2 diabetes is a product of affluence and therefore not as pressing a problem as, say, Aids, which is well established in the minds of electorates as a health concern. As a result, there is likely to be strong political pressure from developing nations to keep the World Bank and WHO’s funds trained on traditional targets.

Diabetes is not simply a problem for developing nations. Recent research has shown that Britain is being overcharged for insulin. The National Institute for Health and Clinical Excellence (Nice), which makes recommendations on drugs, recently estimated that the NHS could save £625m on diabetes treatment. The figure came from a report by Craig Currie, a professor at Cardiff University’s School of Medicine, who found that the NHS was buying complex analogue insulin products—despite the fact that cheaper, equally effective alternatives were available. According to Currie, NHS spending on insulin analogues rose from £18.2m to £305m between 2000 and 2009. In the same timeframe, there was “a decrease in the amount spent on human insulin from £131m to £51m.” In other words, the NHS is buying more and more expensive insulin, and less and less of the cheaper stuff, which is just as effective. The Currie report suggested that the greater use of expensive insulin was perhaps “due in part to successful marketing,” despite the fact that most experts regard the benefits as “modest in comparison to human insulin.”

The US and Canada face similar problems of rising numbers and a struggle to keep down costs. North America spends $214bn on diabetes treatments: 57 per cent of global expenditure on the disease. At present, 11.7 per cent of adult North Americans are diabetic—by 2030 the number will be 13.6 per cent, or 53.2m people. There is no question that the US, Canada or Britain will allow their supplies of insulin to run out. But the increased healthcare costs, the logistical strain of coping with more diabetics of both types and lost economic output will exert considerable pressure on heath services and governments in the years to come.

Nations are not prepared for rising levels of diabetes. A report by Philip Clarke, associate professor at the University of Sydney’s School of Public Health, examined the potential effects of the disease on China. He found that the average amount spent on healthcare each year for each Chinese citizen was $216 (in international dollars). But that jumps to $2,166 for a person with diabetes who then suffers a stroke. China, which already has 43m diabetics, is described in the fourth edition of the IDF Diabetes Atlas as the nation where: “The diabetes epidemic has the greatest potential to explode… simply because of its population size.” India has the largest number of diabetics, with over 50m sufferers.

There is an urgent need for governments across the world to pay greater attention to the cost of insulin, and to place more emphasis on the prevention of type 2 diabetes. If they do not, then the global pricing and supply of insulin will not withstand the coming pandemic. The consequences of this for the west would be economic and for the developing world, humanitarian.

Health services and drug companies must reshape the global supply model, which overcharges the west, and under-supplies developing nations. More, cheaper insulin is needed, and less of the expensive variety. If health services insist on buying cheap, this would depress revenues for the dominant drug companies and help loosen their grip on global supply; more, smaller companies turning out cheap insulin would result. But this would require the overhaul of a well-established and powerful global market—and it will take more than speeches at the UN for that to happen.

[This article has been updated to clarify the distinction between types 1 and 2 diabetes]