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Obesity and the lure of the magic pill

09 September 2013 Praful Mehta

The weight loss industry is growing at an unprecedented rate - with diet drugs, weight loss programs, and unproven methods of lowering weight becoming a common occurrence. There is no shred of doubt that the world we live is getting fatter by every minute (medically defined as the obesity epidemic). And, even more troubling is the general consensus and inclination towards finding a clinical cure for obesity. It seems that people are obsessed with finding a quick fix-or a pill--to solve a complex issue.

I recently watched a very interesting and controversial programme (a four part series) on BBC titled "The Men Who Made Us Thin", which interviewed IHS for its assessment on the pharmaceutical landscape in obesity R&D. I began to think whether the idea and the obsession of having a magic pill to cure obesity will ever materialise. And more so, if an obesity treatment pill will actually solve the underlying problem?

But first, what is obesity?
According to CDC, overweight and obesity are both labels for ranges of weight that are greater than what is generally considered healthy for a given height. For adults, overweight and obesity ranges are determined by using weight and height to calculate "body mass index" (BMI).

While BMI is simple to measure and can be co-related with the degree of fat found in adipose tissues, there is an on-going debate about using BMI as a measure to define individual obesity. By some accounts an estimated 30% those classified as obese are actually healthy in terms of their cardio-metabolic profile, including such things as circulating glucose, insulin, and cholesterol levels.

BMI is an incomplete measure to define individual obesity due to following factors:

  • BMI is a measure of relative weight and hence does not distinguishes between fat mass and muscle mass;
  • BMI does not accommodate for the distribution of body weight; and
  • Treatment strategies based on changes in BMI are slow to implement and hence lead to more treatment failure

Is obesity a disease: The debate rages
In July 2013, American Medical Association (AMA) sparked global headlines across the world by classifying obesity as a disease. The AMA debated that the new designation will increase the focus on obesity treatment and prevention and will help medical professionals deal with the increasingly complex health problems associated with being overweight or obese.

The opposition argues that such a classification can lead to stereotypes and oversimplification. There is great caution that this designation might increase stigma - which ultimately could stifle any progress on behavioural level and might push people to seek more clinical solution to their problem. It will result in medicalization of the problem while increasing the incentive to prescribe drugs.

A disease is defined as: "a state of the body when it malfunctions". With this view, I believe obesity is more of a complicated behavioural, physical and psychological problem than a disease.

I believe we all should take extreme caution, especially when it comes to treating obesity as a problem which can only be resolved with pharmacological or surgical intervention, as it might lead to an uncontrolled pharma race towards finding the perfect pill. As history has taught us, this could have drastic consequences.

A pill for obesity: Can there be magic?
The history of anti-obesity drug discovery research is filled with high profile failures in clinical development, false starts, and adverse events. Moreover, drugs, which were once hailed as the next big breakthrough later proved out to be very disastrous.

In the past (and some current development approaches), pharmaceutical companies have placed greater emphasis on endpoints in clinical trials (reduced body weight / BMI etc.) rather than on the whole process - how the endpoint has been reached.

Most of the earlier drug development strategies have focused on one or more common pathways. However, since obesity usually develops due to interaction of multiple physical, psychological, and metabolic pathways, strategies which only focus on one area usually have a limited scope of success.

In order for any new obesity drug discovery programme to succeed it must be driven by detailed behavioural analysis that looks at the effect of the drug on learning, memory, sexual behaviour, and other cognitive functions. New programmes must identify - through genetic screening - high risk subpopulations and develop strategies to develop these new drugs.

Obesity is quickly emerging as a large social, cultural and clinical problem. It not only increases the risk of other diseases but also increases the overall burden of cost within healthcare systems. It is, therefore, very important to find a long-term solution to the problem. In our pursuit of finding the perfect elixir we must not oversimplify and medicalise this behavioural, emotional, and psychological problem. I believe solutions - implemented at a national policy level - which target behavioural change have a much greater chance of success than any pharmacological magic pill.

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