ReviewHome blood glucose biosensors: a commercial perspective
Introduction
Despite the many technological advances in biosensor research and development and the introduction of many different products, glucose biosensors still account for approximately 85% of the current world market for biosensors, which has recently been estimated to be around $5 billion (Newman et al., 2004). The reasons why the glucose market was particularly receptive to the introduction of biosensors are numerous, but the single greatest factor was the prevalence of diabetes in developed nations.
Diabetes is a metabolic disorder, in which the pancreas underproduces or does not produce insulin. Because cells need insulin to absorb blood sugar (glucose) for their energy needs, the cells of people with diabetes suffer from a shortage of glucose, while glucose levels build up in the blood. The disease is a major world health problem. It is estimated that there are over 170 million diabetics worldwide (WHO, 2004). Worse still, incidence of the disease has risen by an alarming 11% over the last 5 years, and a further doubling of new cases is predicted in the next 25 years (Table 1). Increasing obesity, a more sedentary lifestyle and the spread of western eating habits (high fat, salt and sugar content) are believed to be the major causes of this.
There are three types of diabetes:
- 1.
Type 1 diabetes usually affects the young and occurs when the pancreas no longer produces any (or very little) insulin. Approximately 10% of diabetics have Type 1.
- 2.
Type 2 diabetes commonly affects middle-aged or older patients and occurs when the pancreas does not produce enough insulin or when the body does not use the insulin that is produced effectively. 90% of people with diabetes have Type 2.
- 3.
Gestational diabetes is a temporary condition that occurs during pregnancy. It affects 2–4% of all pregnancies with an increased risk of developing diabetes for both mother and child.
Diabetes is one of the leading causes of death by disease. When left untreated or improperly managed, the high levels of blood sugar associated with diabetes can slowly damage both the small and large blood vessels in the body, resulting in a variety of complications (American Diabetes Association, 2004), including
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incidence of heart disease is raised between two- and four-fold on average;
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the condition is a leading cause of adult blindness;
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diabetes is responsible for over 40% of all new cases of serious kidney disease;
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over 60% of all non-traumatic limb amputations are due to diabetes;
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diabetes is a major cause of erectile dysfunction.
With careful management, these complications can be delayed and even prevented. For many patients, this involves the regular measurement of blood glucose levels. The American Diabetes Association's Consensus Statement on Self-Monitoring of Blood Glucose recommends that people with Type 1 diabetes in intensive therapy should test at least four times a day (American Diabetes Association, 1994). Even people with Type 2 in good control are encouraged to check twice a day. Nevertheless, it appears that frequency of testing is reaching a plateau, or even declining in many countries. This trend is puzzling when one considers the medical benefits of glucose monitoring. It is widely agreed that frequent self-monitoring is an essential and central part of controlling diabetes. This provides data to
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identify trends in glucose control;
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identify factors that may cause high or low glucose values;
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evaluate the impact of activity, diet and medication;
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optimise or change a treatment plan;
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decide what needs to be done when the patient is ill.
It is also possible to relate the patient's general feeling of health to their diabetic condition and, perhaps, alert them to things that may be unconnected to the illness.
This debate is not straightforward, however. One factor that is often overlooked is that the numbers obtained by testing are only one part of the picture, which requires additional data to be complete. For example, it is important to relate the number to what and when the patient last ate. The patient's exercise regime must also be considered, as well as when and how much medication has been taken. If this were not complicated enough, the patient (and physician) need to consider factors such as whether the patient has recently been ill, or even subjected to high levels of stress, which can distort the picture.
For many years it has been assumed that the pain associated with frequent self-testing was the reason why tests were not carried out as often as recommended. There may be some truth in this, but it is clearly not as important a factor as was first thought. The introduction of smaller lancets and alternate site testing has not increased testing frequency. In fact, as was mentioned above, the opposite seems to be happening.
One problem is that many patients do not understand what their results mean. For non-insulin dependent diabetics, where there is often no direct action step, there appears little incentive to monitor and make a record of these results. Even if this was done, there is no guarantee that a physician would have the time, or the ability, to correctly interpret the results due to the complexities mentioned above.
These arguments lead to the crux of the problem – cost. In order to make the extra readings truly beneficial to the patient, proper analysis of the results is crucial. This step is complex and time consuming. It is also, therefore, expensive. The manufacturers of glucose monitors are, of course, well aware of this and have developed data management software to assist with this process. However, patients are reluctant to leave treatment decisions in the hands of a computer programme. Furthermore, there are liability issues to consider as well.
There are, currently, over 40 blood glucose meters on the market. The major players are fighting to accomplish two objectives. Firstly, they need to at least maintain their current market share. Secondly, they need to expand the market itself, to include new users. The lion's share of the market is shared between Roche Diagnostics, LifeScan, Abbott and Bayer. These are very large companies, who have often resorted to a strategy of acquisition, rather than innovation. Consequently, existing technology has often been re-packaged and combined with an aggressive marketing campaign to achieve the above objectives.
As Abbott has discovered, over the last few years, this strategy has a limited lifetime. At the end of 2003, Abbott's Medisense technology, which had been the most innovative and leading edge when it was introduced in 1987 (Turner and Swain, 1988), was, arguably, the oldest and least novel of that offered by any of the major players. To make matters worse, they were losing market share to the “new kid on the block”, Therasense. Abbott announced, in January 2004, an agreement to purchase the smaller, but dynamic Therasense business for $1.2 billion in cash. The deal, at $27 per share, would revive what many analysts and investors saw as a floundering division under the Abbott umbrella. Importantly, it provides Abbott with new, leading edge, and potentially lucrative, diabetes-testing technology.
Competition from reflectance devices continues to diminish, largely because of superior performance of the electrochemical biosensors, with their ability to give a rapid, accurate answer using a disposable strip, with no possibility of instrument contamination. The shift towards electrochemical biosensors has been most noticeable at LifeScan and Roche Diagnostics and explains the huge growth in biosensor sales by these companies over the past few years. It is also significant that the big players are starting to offer glucose with other analytes to increase their market share.
The biosensor market growth has been accelerating over the last 6 years, or so. However, it should be remembered, before one is tempted to extrapolate this trend, that there is a finite limit to the number of blood glucose biosensors that can be sold. A large proportion of the increased sales has resulted from the shift from reflectance technology. On the other hand, very large markets are emerging in countries which have, until recently, not featured heavily in the biosensor sales figures. China, in particular, not only has a huge population (and a correspondingly large number of diabetics), but it has entered the market, initially through the Shanghai New Genius Biotech Co. Ltd. It is almost certain that others will follow in China and in many other countries. It should also be mentioned here that many of the original patents have either lapsed, or will do so shortly. This will, inevitably, lead to a spread of devices, particularly in developing countries.
Section snippets
Glucose biosensor technology
Before discussing glucose biosensors, it is important to mention that the first successful blood glucose meters were not biosensors and that, for many years, biosensors accounted for only a small proportion of commercial sales in this arena.
Initially, the dominant technology was based on a reflectometer invented by Anton H. (Tom) Clemens (1971), whose work led to the launch of the Ames Reflectance Meter (Fig. 1). At the time, Ames was a division of Miles Laboratories in Elkhart, IN, USA, and is
Conclusions and future prospects
In the absence of a cure for diabetes, home blood glucose monitoring will undoubtedly need to continue and the current commercial dominance of mediated electrochemical biosensors will not be easily displaced. While the frequency of testing has faltered in some established markets, new geographical areas are opening up and manufacturers are engaged in fierce competition to maintain and expand market share. New technology has largely arisen in universities and small innovative companies and has
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