An Interview with Dr. Arya Sharma (Continued)
Changing Mainstream Attitudes Toward Obesity
Joseph: One of the big themes in your own work, and in particular in your presentation at the Qsymia Advisory Committee in February, is that obesity is a chronic medical condition like high blood pressure or high cholesterol, even though it's not often seen this way. What do you think will be required to change cultural and medical attitudes toward obesity?
Dr. Sharma: I think a lot of it comes from the public understanding of obesity. As an aside, I'm the Scientific Director and founder of the Canadian Obesity Network, which, interestingly, is the largest professional national obesity non-governmental organization in the world. One of the primary strategic objectives of the Canadian Obesity Network is to address weight bias and discrimination. The reason we've put weight bias and discrimination as our primary goal is because most decisions made around obesity — whether it's management, access to care, public health measures, drug reimbursement, physicians or health professionals wanting to treat obesity, and perhaps even drug approvals — are held back by weight bias and discrimination.
Nobody likes fat people, and everybody thinks it's their fault. Most people don't understand the science and the biology behind obesity. They think this is really a matter of personal responsibility, and if you would eat better and get your butt off that couch, then you would be fine. As long as the public and government and everybody believes that to be true, you are not going to have the same kind of level playing field that you'll have for hypertension or depression or any of those other conditions.
That's going to have to change. It's not a question of having better data. Organizations like the Canadian Obesity Network, or in the US, the Obesity Action Coalition or The Obesity Society, have to step up and educate the public and the decision-makers. Obesity is not merely an issue of self-responsibility, there's actually a very complex biology here. Even if you were highly motivated to lose weight, your chances of keeping it off are actually pretty slim. Those are the messages that actually need to get out to decision-makers.
Joseph: The prospect of long-term weight loss in the population as a whole seems very challenging based on most interventions for which we have long-term data. Assuming that we turn this around in the next 50 years, what do the turning points have to be? Will it be better therapy? Some really refined and effective surgery? Impacting childhood obesity?
Dr. Sharma: If I had to bet, I'd bet on drugs and not on surgery. I think surgery is a phase. It's being done now; it'll be around for probably another decade or so, maybe longer, until we get new drugs.
I think that there are two things that may need to change in drug development, or even in the thinking about pharmacological treatment of obesity. The first is starting to differentiate obese people into subsets of obese people. So a drug that doesn't have to be for whoever has obesity, but rather for a subset of patients with obesity because they have a certain eating disorder or there's a certain pathway in their brains that is promoting overeating or they have a certain lack of satiety. That is a group of patients for whom a given drug really works. They are the ones who should be getting it. The drug may not work for everybody else. You would start splitting down this whole indication into other groups.
That may or may not happen. In hypertension, it never happened. We have 100 drugs for hypertension and people have always said, "Let's break it down and let's decide who's the best patient for a diuretic and who's the best patient for a beta blocker and who's the best patient for an ACE inhibitor." That actually never worked. In the end, even today, hypertension practice is pretty much trial and error, with fixed combinations becoming more and more accepted. So, I'm not holding my breath that that will happen with obesity. I think if you find drugs that are overall effective and well tolerated in most people or at least half the people you treat with them, it probably doesn't matter.
But I think the other piece that really matters is whether or not we can come up with a way to license drugs to help with weight-loss maintenance. The mechanisms that help you lose weight may not be the same mechanisms that help you keep weight off. Take leptin, for example. Leptin is not a great drug for losing weight, but it may be the perfect drug to keep weight off. But there's no regulatory pathway. If I wanted to license leptin for weight management, I would have to go to the FDA and show that it helps people lose weight, which it doesn't, and so I'd never be able to license it. I need a regulatory pathway that's going to allow me to specifically get regulators to approve a drug that is efficacious for helping people maintain weight loss, even if it does not promote weight loss in itself. So, the idea is you go lose weight and come back to the doctor's office, and then he'll put you on these drugs so that your weight doesn't come back. That is a regulatory pathway that doesn't exist right now.
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There are very few conditions under which I will not ride my (road) bike. More than an inch of new snow, snow pack, and slush are the three major ones. That said, if the distance is short and familiar, and traffic is expected to be light, I'll take my chances. I was considerably less hesitant in my teens and twenties when I had two bicycles in my stable: a three-speed commuter and a 12-speed touring bike. My craziest experiences then were riding through what I later...