Close Concerns: Stopping The Gain

Earlier this week, the influential healthcare information firm Close Concerns published a rather lengthy interview regarding my take on a wide range of issues related to the future of obesity management. The interviews were conducted by Joseph Shivers, Vincent Wu, Lisa Vance, and Kelly Close, who certainly challenged and stimulated my thinking with their well-informed questions.

The following is another brief excerpt from this interview published in their newsletter Closer Look:

JOSEPH: Is figuring out what obesity drug works for which person a matter of differential diagnosis? For instance, already we hear about personalizing drugs to a great extent, i.e., if patients are very hungry, then phentermine might be better for them, etc.

DR. SHARMA: Yeah, there’s some of that. But again, I worked in hypertension for 20 years, where people have been trying to find that kind of link between the pathophysiology and the drug, and they’ve never figured that out. So I’m not holding my breath that this would work for obesity, although I’m sure people will be trying and there might be subsets where it might work.

Unfortunately, we don’t currently have an etiological framework around obesity that opens up different pathways. Consider someone for whom overeating is more of an addiction problem. Drugs targeting addictive type of behavior would be more effective for that patient than in someone for whom overeating is a time-management problem: if you allow yourself to get hungry and that’s when you overeat. That is not going to be fixed by using a drug – unless perhaps the reason that you’re skipping meals and forget to eat is an underlying attention deficit disorder, which I could treat to help you better organize your meals and thus better avoid those hunger situations.

Then if you take obesity in the elderly, for example, it’s most often related not to overeating, but to a lack of physical activity and other factors that may be approached in a very different way. There are lots of different reasons why people gain weight.

But when you think about why people ‘regain’ weight, the story is very different, because irrespective of how you lose weight, the biological drivers of weight regain are pretty much a common denominator for everybody. So, regardless of how I lose weight, my leptin levels are going to drop, my appetite is going to go up, my hunger level’s will go up, my metabolism’s going to slow down. All of these common things – which will happen in anybody who loses weight for any reason – are going to drive me back toward my original weight or ‘set-point’.

That is also the reason why developing weight-loss drugs to address the underlying etiological drivers of weight gain might end with a whole bunch of different drugs that do different things. But when it comes to a drug or drugs that prevent weight regain, you might actually be able to have a common drug, because you have common mechanisms that drive weight regain. And that’s a very fundamental – you could say almost philosophical – way of thinking about these things.

JOSEPH: You’ve talked about many different etiologies for initial weight gain. Would you say that those are truly all different, or might they all be manifestations of an underlying disorder that shows up in different ways but ultimately motivates overeating?

DR. SHARMA: No, I think that you’ve got two things. One is a genetic predisposition, where people who have the same stressors and same behaviors, will have a different rate of weight gain.

But even when you take people who are just overeating, you will find lots of different reasons why people will overeat: time management, using food as a coping strategy, lack of knowledge about how many calories they’re consuming, peer pressure, customs, beliefs, culture, not enough money, food insecurity, etc.

Those are the social drivers of obesity, some of which you can approach pharmacologically. But for a lot of these, the underlying problem is not an obesity problem. So, if you take somebody who is self-medicating their depression with food, after getting treatment and better control their depression, they’ll get better control of food intake. That is not necessarily a weight-loss drug or a weight-loss approach, but it is part of obesity management. Managing depression or managing mood disorder is a part of care, in someone who is treating their mood with food. Simply slapping on a drug that, say, increases their metabolism or reduces their appetite, without addressing their mood problem, isn’t a medically sensible thing to do.

There’s one caveat here, which I think is important. This is fundamental, but I find that a lot of people don’t get this: if mood is the factor that is causing weight gain, treatment is not necessarily going to give weight loss. Let me give you a typical example. If I diagnose binge-eating disorder in someone and that person stops binging, I don’t necessarily expect to see weight loss. What I expect to see is that this person will stop gaining weight.

You could say the same for a lot of things. Take a patient who’s been gaining weight because severe osteoarthritis in their knee made them reduce walking. Typically they won’t lose weight when they get their hip or knee replacement. They stop gaining weight. I can give you a whole bunch of examples, but the common thing that happens is that you find what’s causing the weight gain and remove it. What you’re actually removing is the driver of weight gain, which means that weight gain stops. It does not mean that when you stop weight gain you end up with weight loss.

That’s a very important distinction, because a lot of people think that if they stop doing what is causing their weight gain, they should somehow start losing weight. In fact, a lot of people are really disappointed. Then they say, “Well, you know what, I used to drink pop or I used to eat out a lot, and my weight was going up. Now that I’ve changed my diet and my life style, why is my weight not going down?”

It’s not going down because you’ve only removed what was causing the weight gain. The success of that is that you’ve stopped gaining weight. But that doesn’t mean that you’re now going to lose weight. That is your second step. And I think most people do not, in their minds, and in their approach to obesity, separate the two. They do not say, “Well, let’s first find out what’s causing weight gain and address that. Then now I’ve stopped gaining weight that is a sign of success, because I can define what the problem was and we’ve solved it. Now, let’s go to the next step and see about how we can get some of this weight off.”

We don’t normally think of this as a two-step process. And then of course there’s the third step – keeping the weight off!

To be continued….

Copenhagen, Denmark