Can The Edmonton Obesity Staging System Provide A Path For New Anti-Obesity Drugs?
Monday, August 22, 2011
As readers of these pages are well aware, there is currently only one prescription drug (orlistat) for the long-term management of obesity and recent applications for new anti-obesity drugs have run into considerable obstacles with licensing agencies, not least the US Food and Drug Administration.
Thus, despite meeting criteria for efficacy, recent applications for new anti-obesity drugs were rejected due to safety concerns, the argument being that the expected widespread use of these drugs warrants higher standards of safety than for drugs in other therapeutic areas.
This may well be true, if anti-obesity drugs are indeed to be made freely available (even on prescription) and are to be used without careful consideration of the risk/benefit ratio.
As discussed previously in the context of bariatric surgery, the risk side of this equation is not limited to the ‘risk’ associated with treatment but must also include the ‘risk’ associated with not treating the condition.
As our recent papers on the Edmonton Obesity Staging System (EOSS) clearly show, the ‘risk’ associated with obesity varies considerably – from virtually no risk for patients with EOSS 0 to very significant and immediate risk for patients with EOSS 3.
So, while even the smallest treatment-related risk may be unacceptable for treating obesity in a patient with EOSS 0, a higher level of risk would be certainly be acceptable with higher EOSS stages – or in other words – the greater the risk of not treating, the greater the acceptable risk for a potentially beneficially treatment (which, for e.g., is why cancer warrants the considerable treatment risks of chemotherapy).
Of course, this would mean that rather than having to prove the safety and efficacy of anti-obesity drugs in anyone with a BMI over 30, it may be enough to show that these drugs are effective and safe enough to warrant their use in people with higher EOSS stages (2/3) – the greater the risk of the target population, the greater the acceptable risk of treatment.
This should not be difficult. We know that many of the conditions that patients with EOSS 2/3 present with can be ameliorated even with rather modest weight loss. For these patients, the 5-10% sustainable reductions in body weight that can be achieved with anti-obesity drugs, can have very significant health benefits, which would easily outweigh and justify a reasonable risk of adverse effects – a risk that may be unacceptable in patients presenting with EOSS 0/1 obesity.
This, of course means rewriting some of the approval criteria and guidelines for anti-obesity drugs, but also requires redesigning pharmacological trials to focus on the high-risk EOSS 2/3 patients rather than on the low-risk EOSS 0/1 patients.
I certainly look forward to following how this discussion evolves and wether or not we can indeed find a way out of the current impasse of anti-obesity drug development and approval.
AMS
Toronto, Ontario
Padwal RS, Pajewski NM, Allison DB, & Sharma AM (2011). Using the Edmonton obesity staging system to predict mortality in a population-representative cohort of people with overweight and obesity. CMAJ : Canadian Medical Association journal = journal de l’Association medicale canadienne PMID: 21844111
Kuk JL, Ardern CI, Church TS, Sharma AM, Padwal R, Sui X, & Blair SN (2011). Edmonton Obesity Staging System: association with weight history and mortality risk. Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme PMID: 21838602
Tuesday, August 23, 2011
As discussed previously in the context of bariatric surgery, the risk side of this equation is not limited to the ‘risk’ associated with treatment but must also include the ‘risk’ associated with not treating the condition.
The problem is, the health risks that fat people have are not hard wired to their weight, and will not necessarily be be reduced by weight loss. I don’t know of any studies that strongly support the assumption that weight loss improves real health outcomes for fat people. That’s why the bar needs to be so high for weight loss drugs. A drug like Redux can cause heart valve damage and shorten the life of someone who may otherwise have lived to 100. And for what? A fifteen or twenty pound weight loss that wouldn’t even move most fat people into a lower risk BMI category, let alone do anything to remove the social stigma they face (and trying to change the victim when the problem is with the bias is disturbing at best).
This is why the weight based paradigm is so dangerous. When you start to view something that, healthwise, is nothing more than a risk factor as a disease, you start to think it’s okay to subject people to risky treatments that you think may put them into a lower risk group. And, with the strong stigma attached to fatness in our society, you’re going to have a lot of people who are willing to put their health and lives at risk in order to make their bodies more socially acceptable. Since fat people will often prioritize weight loss over health, this makes doctors and government regulators the gatekeepers for the potentially dangerous weight loss methods. Unfortunately, doctors and regulators also buy into the social stigma, and it can be a powerful, not entirely conscious influence.
I think we agree that giving a healthy fat person a weight loss drug or treatment that might kill them is a bad idea. But, I’m not sure if it’s a better idea for fat people who aren’t perfectly healthy – not unless you have clear evidence that the method improves long term health outcomes.
Thursday, August 25, 2011
Many studies show that a variety of hormones play a large role in obesity, and yet doctors seem only to test the thyroid. I would like to hear your theory about this, as when I attended one of your talks you started by mentioning Leptin.
Therefore, would a thorough hormone screening test not be of value in helping to assess the obese?
Many people blame the hormone additives given to cattle as the cause for our youth to physically mature earlier, and for the rise in occurence of cancer. Is the human body adapting to our culture of added salt, hormones and fertilizers? For years I have heard that Canada was going to regulate the amounts of salt allowed in our pre-fab / fast food / junk food items. I think there are many other issues in our food industry to be addressed, and when will this ever happen?