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Thursday, November 22, 2007

Kudos to Dr. Padwal!

At least publication wise, this has been a great week for our Dr. Padwal.

In an article published in the BMJ he analysed the overall utility of anti-obesity drugs. The bottom line is that on average the results of using these drugs, when assessed by the magnitude of weight loss compared to placebo, is rather modest.

Of course this story was widely picked up by the media (click here for TIME Magazine's take on this).

In the October issue of IJO Dr Padwal also had a paper on adherence to anti-obesity meds (click here for the link to PubMed). The bottom line here was that although effective, most people take their medications only for a few months, after which weight comes back.

Both articles raise important issues regarding obesity treatments in general.

1) Should "average" efficacy determine choice of therapy?

When dealing with a condition that is as heterogeneous as obesity, can any single non-pharmacological (lifestyle) or pharmacological intervention be expected to produce dramatic average effects?

For e.g. cognitive behavioural therapy (CBT) appears to work well for people with binge eating, but there is little evidence that it works for obesity in general.

Similarly, sibutramine, which works largely by enhancing the physiological satiety response to eating, works in some patients but not in others. So for e.g. I frankly do not expect sibutramine to work in patients where poor satiety is not the problem (e.g. in hedonistic eaters), in people who are eating too fast to allow their physiological satiety response to kick in (by which time, they have already consumed too many calories), or in people who have no physiological satiety response (e.g. mutations in the MC4 receptor).

In clinical practice it is common experience that individual patients will do better on one treatment than on others (in fact, we call that "personalized" medicine).

It is important to realise that when dealing with an epidemic, even a small fraction becomes a large number of patients. So even if only 20% of obese patients do well on CBT, sibutramine or orlistat (and these are most likely a different 20% for each treatment), respectively - that still means that these approaches could be effective in millions of patients.

I believe that the problem with obesity treatments in general is not that they do not work - the issue is that all treatments just don't work for everyone!

Identifying patients for whom specific interventions work better than others remains a key challenge although there have been pragmatic suggestions: if one treatment does not work - try something else!

2) Should treatments be abandoned because patients don't stick with them?

This is not just an important question to ask about pharmacotherapy (as Dr. Padwal did in his IJO paper). The question is as relevant to non-pharmacological treatments.

So if the majority of patients will not adhere to a given treatment in the long-term (we call this attrition), should we completely abandon using this treatment?

Of course not! Thus, although there is little evidence that the majority of patients will stick to lifestyle treatments in the long-term, some people will (e.g. the folks on the National Weight Loss Registry) and for them this approach is reasonable. For the rest, we are going to have to do better.

The case for pharmacotherapy is not different. Just because most patients will not take their anti-obesity drugs forever, does this mean we do not use drugs at all? Some patients will stick to their medications and for them this is certainly an effective treatment.

Incidentally, it may be worth noting that there is nothing unique to obese patients in terms of not sticking to treatments - this problem is universal to all chronic diseases. Thus patients with hypertension, diabetes, high cholesterol and even patients with painful conditions such as rheumatoid arthritis are notorious for not sticking with their prescribed treatments for more than a couple of months.

I believe that as patients, health professionals and regulators move towards thinking about obesity as a chronic disease rather than something we can "fix" with a short-term approach and as we fully realise that in obesity management "one size will not fit all", we will eventually become more effective (and realistic) in dealing with this condition.


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