Commentary: Politics of affordable insulinBMJ 2011; 343 doi: https://doi.org/10.1136/bmj.d5675 (Published 14 September 2011) Cite this as: BMJ 2011;343:d5675
- Edwin A M Gale, emeritus professor of diabetic medicine1,
- John S Yudkin, emeritus professor of medicine2
- Correspondence to: E A M Gale
The diabetes pandemic increasingly affects low and middle income countries, where most of those affected have type 2 diabetes. Cheap generic versions of current first line treatments, metformin and sulfonylureas, are widely available so why does this not apply to insulin?
Human insulin is off patent, is relatively simple to manufacture, and WHO recently included it in its list of essential medicines in preference to analogue insulin.1 Generic biosynthetic human insulin would bring down the price of insulin, and several companies have the capacity to produce it, but progress has been confounded by claims that branded analogue insulins—which are typically two to four times the cost of branded human insulin—are better treatment.
This claim does not relate to biological action, for the analogues are simply delivery systems designed to speed or smooth the rate at which insulin reaches its receptor from the injection site. Although these properties are valuable in some situations, Cochrane type reviews of the use of human and analogue insulins have found limited evidence of benefit in type 2 diabetes 2 3 and NICE has reaffirmed that human insulin should be considered first line therapy in this condition.2 Only one study, on people with type 1 diabetes, has compared analogue and human insulin in double blind fashion. This found no change in haemoglobin A1c and a small reduction in nocturnal hypoglycaemia. The participants were unable to tell the insulins apart at the end of the study and expressed no clear preference either way.4 In the absence of similar blinded trials in type 2 diabetes, it seems unlikely that these patients would notice a difference either.
If the case for analogues cannot be based on efficacy, it certainly cannot be based on cost. The clinical advantages of analogues may be sufficient to justify a modest mark-up if we use value based pricing, but they are surely inadequate to justify an excess of 200-400%.
The case for generic insulin seems clear, so why the delay? One reason is that insulin is big business. Global sales rose to a predicted $11.8bn (£7.4bn; €8.4bn) in 2010, as against $2bn in 1995,5 and insulin accounted for 48.4% of the UK drug bill for diabetes related prescriptions in 2008.6 Indeed, data released last month suggests that diabetes now accounts for nearly a tenth of the annual NHS drugs bill in England.7 Most of this increase was due to increasing use of more expensive analogue insulins, and the three companies now dominate the world insulin market.
The cost of insulin
But even the cost of human insulin varies widely across the world. On 11 May 2010, volunteers from 60 countries visited their local pharmacies to buy 10 ml of 100 IU/ml human soluble insulin. The price varied by a staggering 5000%, and by 2900% for the same brand.8 Much of the difference was due to profit taking by pharmacies and other in-country suppliers rather than to factory price, but the fact that branded human insulin is sold in some markets at less than $5 a vial provides some indication of the true manufacturing costs.
The insulin manufacturers have been prominent in the campaign to make cheap insulin available to some of the world’s poorest countries, despite difficulties such as the re-export of donated insulin for sale elsewhere.9 10 Nevertheless, children still die because of lack of affordable insulin,11 and the insulin oligopoly remains part of the problem, rather than part of the solution.
The companies are not to blame for this, for they are commercial organisations and must inevitably pursue commercial goals. Their mission is to develop new products, to promote these at the expense of the old, to seek new markets, and to sell their products for the best price the market will bear. They will naturally avoid mutually harmful price cutting. When it comes to diabetes, it has been equally natural for them to support the use of intensified glucose lowering strategies, which inevitably include earlier and more aggressive use of insulin.12
Representing the public interest
Open competition between branded and generic insulin, waged in terms of cost and evidence of efficacy, would undoubtedly be the most effective way of driving down the price of insulin, and would also make charitable donations unnecessary. The analogues are undeniably popular with patients and physicians, but they are overpriced, and they have been promoted well beyond the limits of the evidence. Wealthier nations may be willing and able to sustain the excess cost, but people elsewhere are dying because of lack of insulin or enduring unnecessary hardship in the struggle to afford it.
So where are the advocates for cost effective insulin and evidence based guidelines? The WHO Essential Medicines and Supplies Program issues an updated essential medicines list every two years, but neither it nor the non-communicable disease division has generated evidence based guidelines that are applicable to a wide spectrum of socioeconomic settings. The main income of the International Diabetes Federation (IDF) derives from its biennial World Diabetes Congress, and much of that income is generated by the pharmaceutical exhibition. IDF Africa recently coordinated the first East African diabetes summit to help identify sustainable models for dealing with diabetes, but the programme was heavily dominated by drug industry symposiums, implying that the federation endorsed the advocated strategies. The federation’s dependence on industry may leave it somewhat emasculated when commercial strategies need to be confronted.
Obstacles to affordable insulin
The drug industry is a major source of information about patient management throughout the world, and the dominant source in low to middle income countries. Doctors and specialist nurses attend conferences and symposiums with industry support and learn about the latest advances in patient care, which typically relate to newer patented drugs that are much more costly than medicines on WHO’s essential medicines list.1 The pressure on limited resources may be such that essential medicines, including insulin, can no longer be afforded.11
Would-be manufacturers of generic insulin face many challenges. One is the capital costs to establish bioengineering facilities. Another is the lack of a marketing force to compete with the huge investment of the insulin giants. Yet another is the lack of suitable delivery devices, since the uptake of new insulins is often driven by the quality of the pen devices that contain them. And, finally, there is not yet in place a WHO prequalification scheme for insulin, as exists for antiretrovirals and antibiotics,13 to confirm manufacturing quality. But entrepreneurial ingenuity will, if offered a level playing field, soon overcome such obstacles.
In the last analysis, the main obstacles to generic insulin seem to be a failure of will and an inability to face the facts. Professional societies such as the IDF have yet to commit themselves to advocacy of the only course of action that will guarantee the future of affordable insulin, and we can only wonder why.
Cite this as: BMJ 2011;343:d5675
Competing interests: All authors have completed the ICJME unified disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare no support from any organisation for the submitted work; no financial relationships with any organisation that might have an interest in the submitted work in the previous three years; and no other relationships or activities that could appear to have influenced the submitted work.
Provenance and peer review: Commissioned; not externally peer reviewed