What Surprised Us Most About GLP-1 Medications and Obesity Management

James Hill:
Welcome to Weight Loss And, where we delve into the world of weight loss. I'm Jim Hill.

Holly Wyatt:
And I'm Holly Wyatt. We're both dedicated to helping you lose weight, keep it off, and live your best life while you're doing it.

James Hill:
Indeed, we now realize successful weight loss combines the science and art of medicine, knowing what to do and why you will do it.

Holly Wyatt:
Yes, the “And” allows us to talk about all the other stuff that makes your journey so much bigger, better, and exciting.

James Hill:
Ready for the “And” factor?

Holly Wyatt:
Let's dive in.

James Hill:
Here we go.

Holly Wyatt:
We have spent decades studying obesity and weight management, and I think it's fair to say that these new medications have changed some of our, I would say, our fundamental assumptions.

James Hill:
Holly, I've seen treatments come and go, but I've never seen anything quite like this.

Holly Wyatt:
So today we're going to do something a little bit different. We've each picked five things that genuinely surprise us about the GLP-1 medications or about the obesity field now.

James Hill:
Yeah, you know, after all these years, it's amazing that you and I can still be surprised.

Holly Wyatt:
Yeah, definitely. Some of these surprises are going to be about the science. Some are going to be about what we're seeing in our patients. And some are about what we thought these medications would solve, but maybe they haven't.

James Hill:
Well, let's see if we can surprise each other, Holly.

Holly Wyatt:
All right. 10 things that surprised us. Jim, you're going to go first. Your first one.

James Hill:
I'll go first. So my first and biggest is we never imagined medications that could produce weight loss approaching results seen with bariatric surgery. For years, Holly, we had lifestyle down here at the bottom, bariatric surgery up at the top, and there was a huge gap between the two. With these medications, we've gone from lifestyle producing 5% to 10% weight loss to now average weight losses with the medications approaching 20%, 25%, and with new ones coming on the board, perhaps even as much as 30%. This is a big surprise.

Holly Wyatt:
Yeah, me too. This is a surprise. I can't remember. I know how many slides I put together, and it was almost kind of three tiers. It was like lifestyle at the bottom. And then we would try to push that up a little bit. And then medications were a little bit more.

James Hill:
But not much.

Holly Wyatt:
Yeah, it was like three tiers, right? And I think we were always hopeful that the medications would improve, but I don't think I ever thought they would get up there to the top tier by bariatric surgery?

James Hill:
At least this quickly. You'd said, well, in 50, 100 years, maybe. But in my career, going from the best we could do without surgery to 10 percent to now 20, 25, 30 percent in such a short period of time, this is a big surprise.

Holly Wyatt:
A surprise for me. For the first time, And I'm asking people, we're asking people whether they can lose too much. We're thinking about, can people lose too much weight?

James Hill:
I never in my wildest dreams thought we would ever ask that question.

Holly Wyatt:
Yeah, we've spent our careers trying to help people lose more weight, as much weight as possible. And this whole idea now that we have the maximal weight loss may not be the optimal weight loss. And that whole thought process is just different for me and very much of a surprise. And I catch myself going back into my old thought process. I'm like, wait a minute. I need to think about this difference. So the idea that you can produce too much weight loss and we need to dial that back in. But I do want to say one thing because I've been saying this on some other podcasts and I've gotten some emails back saying, “Well, the medications don't work for me.” So I do think we need to talk about that, that 20% or more are non-responders or there are people who have side effects that aren't tolerable. So we're not there for everybody. But Jim, I think we're going to get there eventually.

James Hill:
Well, I think we're going to have so many options to choose from. Right now, we have two, basically. I think very soon we're going to have three, then four, five, six. So I'm actually fairly optimistic that within the very near future, maybe one to three years, we're going to have an option that works for just about everybody.

Holly Wyatt:
Yeah. And you're going to be able to use ones that maybe the side effect profile is better for you. We're going to be able to have just more choices. So maybe we're not quite there yet for everybody, but I think we're going to get there too.

James Hill:
I agree.

Holly Wyatt:
Yeah.

James Hill:
All right. Number three. We can suppress appetite and food intake so powerfully for so long.

James Hill:
Now, Holly, this is a real surprise because everything I know about food intake is the biology is so strong that you can suppress it for a little while, but it's going to come back. And we saw that with lifestyle programs. People can reduce their food intake temporarily, but without the medications, we've never seen them to be able to do it so easily for so long. So this is a real, real surprise for me. The data suggests that as long as people stay on these GLP-1 medications, food intake remains low. And in a way, it's not hard for people to eat less. Whereas with lifestyle, it was hard. With the medications, they eat less and it's not hard.

Holly Wyatt:
I think for me, I've always taught this, that the appetite regulation is so redundant, that there's so many different pathways.

James Hill:
So many mechanisms to get you to eat.

Holly Wyatt:
That if you blocked one or even two, or, you know, that the body would respond with other pathways to kind of make up for it to not allow you to lose up to that 30% weight loss that we may see, that bariatric surgery level. And if you think about it, this makes sense with what we talked about at the beginning. Bariatric surgery could produce these high levels. Why? Because they went in and made anatomical changes to your gut. I mean, permanent changes

James Hill:
Permanent structural changes. This is suppressing appetite without any apparent permanent structural changes. And that is a surprise.

Holly Wyatt:
I would have thought if you went in on one pathway or even two pathways, some other pathway would take over, right? That's, that's to me the biggest surprise that we can do this so powerfully for so long, I never would have thought that we could do that to appetite, that it would come back.

James Hill:
Amazing.

Holly Wyatt:
Yeah. All right. Number four, losing weight doesn't automatically mean eating better or moving more. And I know we talked about this in our last couple episodes, but Jim, I'm still just, I'm not over it yet. I'm still surprised by it.

James Hill:
I guess I'm not surprised as much as disappointed. Again, when these meds came out, I read all these articles about how it was going to change everything. People are going to be out looking for healthy food. The gyms are going to be overflowing. And that has not happened. And for me, Holly, this is much more of a disappointment than a surprise. Because I was hoping as people weigh less, they feel better, their knees and joints don't hurt, maybe they're going to get out and move. And now that they've lost weight, they want to be as healthy as possible. And what we're finding is, that doesn't happen just on its own.

Holly Wyatt:
I guess I believe they would, Jim. So maybe that's why I'm surprised. But it's like, okay, let's change the physiology, which we're doing with the drug. And that kind of levels the playing field, which absolutely is true. It's not cheating. It's leveling the playing field. And now with that level playing field, we're going to go out and we're going to be able to make better choices. We're going to be able to move more. We're going to be able to go to the gym and it's not going to hurt as bad.

James Hill:
I know. I know. But again, to put a more positive light on this, I think it's more evidence that while these medications are amazing, wonderful tools, they alone aren't going to get people where they need to be. It's the medications plus. And I think it's the plus that we have to work on helping people understand.

Holly Wyatt:
Yeah, that it's not going to automatically happen.

James Hill:
It's not going to automatically happen. We argue about the role of lifestyle in the GLP-1 era. And in my book, Holly, it's never been more important. But it's different. Those of us who are interested in lifestyle have to understand that we need to change our approaches here. Nutrition now doesn't need to be about weight loss. It needs to be about optimizing health.

Holly Wyatt:
Yeah. And I do think, even though I'm surprised or disappointed... I think if we're aware, it's still a good thing because if your knees don't hurt, then it's going to be easier or at least more enjoyable to go out on a walk.

James Hill:
So the idea is if we're looking, for example, at interventions to increase physical activity, should be better in people that have lost weight than people that haven't. And those are the kinds of things we need to see if that's true. We need to do those studies.

Holly Wyatt:
Yeah.

James Hill:
Number five is maybe not surprising to me, but I think it's surprising to a lot of people. We have effective weight loss medications, but they haven't solved all of our weight management problems. For years, I think people undergoing weight loss felt like just reaching that number on the scale was all they needed to do. The other stuff would come along. They would be better socially. Their friends would like them more. They would be happier, all this. And what we've learned is that simply reaching that weight goal, which the meds are very effective at, that's not solving all of our weight management problems.

Holly Wyatt:
Yes, I know several people came to me and said, okay, Holly, you know, you've been helping people lose weight your whole career. These meds, what are you going to do now? You're going to have to shift your career. And at first I was like, well, maybe they're right. And I don't think that's the case.

James Hill:
That happened with leptin when people told us we needed to get another career. I think we're okay for a while. A great example is on the nutrition side. Now we're seeing nutrient deficiencies because these meds help people eat so much less, they're not getting adequate nutrition. So again, it's like everything else. There's so many wonderful aspects here, but there are some negatives that we need to be aware of and address. And I think this is a huge leap forward is to understand just reaching the number on the scale is only part of the success that we want people to have.

Holly Wyatt:
Yeah. I also think this is going to bring us to really start to look at is maintaining a lower body weight, lower body fat at a low level of influx or flux, I guess, you know, where you're eating low and you're moving low. That's what I mean by low level of flux through the system. You know, you're maintaining balance, but not by eating a small amount, by moving a small amount versus eating more and moving more. Is that really, what does that mean from a health standpoint? I don't know that we know that.

James Hill:
Well, actually, Holly, I probably should have listed that as my biggest surprise. I have always thought that the key to long-term weight loss maintenance is achieving energy balance at a high flux. And we see that in the National Weight Control Registry. These people exercise a lot, so they aren't just using food restriction. And I would have told you that it's impossible to maintain weight loss at low energy flux, which means low energy in and low energy out. But with these medications, it looks like that's happening, at least in the short term. And I'm very interested in the long term in whether that stays the same or not.

Holly Wyatt:
And is that good for you? Or does that low level of flux affect other systems?

James Hill:
Well, again, the idea of don't just focus on body weight. Perhaps at an energy balance, at a low flux, you can maintain body weight.

James Hill:
But are you maintaining the other benefits that we want in weight management?

Holly Wyatt:
Yeah. All right. Number six is a big one for me. And if there's some endocrinologists listening, I would love your input on this. This is something I've thought a lot about. So one surprise is that when we sustain GLP-1 receptor stimulation, so we put these medications, they're analogs, they sit on the receptor and, it has what I'm calling a surprising favorable therapeutic window. And what I mean is it looks predominantly really, really good, and there's not very many downside. And let me explain what I mean. When I look at other hormonal systems in the body like thyroid, cortisol, any other hormone, even growth hormone if there's not enough, we always want to replace it as endocrinologists

Holly Wyatt:
It's a bad thing, right? Not enough of a hormone. But too much of a hormone is also a bad thing. And we always then want to try to suppress it or get rid of it, depending on why it's high. We do different things. But we're always, every hormone, there's positives and negatives. And negatives when it's too low and negatives when it's too high. But for these GLP-1 system, it doesn't seem to be like that. It's like when you take these medications, the levels are very high. It's stimulating at a very high level, like you would have extreme high levels of constant GLP-1 around. And yet, the risk seems to be pretty low at this point. That's not normal, I think, in a hormonal system.

James Hill:
Well, in some ways, it's almost too good to be true, isn't it?

Holly Wyatt:
Yeah.

James Hill:
Because elsewhere, where you've used one hormone to get a huge effect, you see some negatives in other systems. And we don't seem to be seeing that.

Holly Wyatt:
Yeah. So like growth hormone, if you don't have enough, we want to replace it. If you have too much, we see problems with your heart. We see growth in other tissues that's not good, in your colon. And I mean, there's always this plus minus, this risk-benefit profile that we're looking at. And GLP-1 seems to be really unique. So I don't know.

James Hill:
That's truly a surprise.

Holly Wyatt:
Yeah.

James Hill:
All right, number seven, and this is a surprise. Losing tremendous amounts of weight doesn't necessarily produce quality of life improvements as expected. And I'll have to say, I thought it would improve a little bit. And the data coming out, and again, to be fair, we need more data, but the data coming out suggests that people that achieve these high levels of weight loss aren't seeing an improvement in their quality of life.

Holly Wyatt:
I think a little bit. We did a show on this, Jim.

James Hill:
But it's almost negligible. I had thought there would be a bump up. I didn't think it was going to make their life wonderful. But I thought it would produce a bump up. And again, this is both surprising and disappointing.

Holly Wyatt:
Yeah, I wonder if we're measuring the right thing, though.

James Hill:
No, I know. And I think, you know, one of the good things about these meds, Holly, is because now we're having people reach their weight goals, we can start looking at other outcomes other than weight. Because for so many years, we just focused on getting to a weight goal. And I think better ways of measuring quality of life, what aspects of quality of life may be important. And then the other thing, how can we add other interventions along with the medications that impact quality of life?

Holly Wyatt:
That's what I like. I think we need to be doing stuff while people are losing the weight to really get at quality of life. It's not going to just happen automatically. I think it can happen, but I think you've got to work toward it at the same time.

James Hill:
Agreed.

Holly Wyatt:
There's another question, Jim. Have we assumed too much about what losing weight will do for someone's life?

James Hill:
Oh, I think so. And I think you and I have realized that for quite a while. People come in and they think losing weight is going to solve all their problems. And in fact, it doesn't. I think the public has assumed too much about the benefits of just achieving weight loss alone.

Holly Wyatt:
I think the field has too. And part of it is we're like, here's a major problem. If we get rid of it, it's going to, what's it going to solve? And we maybe overestimated what it would solve.

James Hill:
The other thing it says, Holly, is most of these meds were developed focused simply on metabolic health. And the fact that it improves metabolic health so much without improving quality of life, I think says that there are other aspects of quality of life that are more or equally important to metabolic health.

Holly Wyatt:
Oh, you know what I would love? I would love for the pharmaceutical companies to actually study that. They've been just studying the drug and the amount of weight loss that it can produce. But some of the new companies that are kind of coming out and saying, okay, I'm going to make a drug, maybe it won't have 30 percent weight loss. But what if it had 15 plus quality of life because you do it in this way. I mean, thinking about how to expand what they're studying? I don't know. It's probably hard to patent that.

James Hill:
I think as a field, we've overestimated the importance of metabolic health to quality of life. Now, don't get me wrong. Metabolic health is wonderful. But I think some of us in the field have said, “Oh, if we lower people's blood pressure and cholesterol and everything, they're going to be really happy.” And again, I think people appreciate that, but it doesn't seem to be translated into big increases in quality of life.

Holly Wyatt:
Well, we still doctors, they're very excited, right? Because of the things.

James Hill:
Exactly. Metabolic health is fabulous. Don't get me wrong. We do need to focus on it. But I think the data are telling us that that's not enough to just focus on metabolic health. Yes, that will improve things, but it's not enough. It's not giving people everything they want.

Holly Wyatt:
Yeah. But how cool is it now we get to focus on that?

James Hill:
Oh, yeah. Absolutely.

Holly Wyatt:
I mean, what an opportunity. I mean, in a way, I'm disappointed, but in a way I'm like, woah.

James Hill:
So we got the weight loss. We got the metabolic health. Now let's focus on some other things.

Holly Wyatt:
Yeah, we now get to do this.

James Hill:
This is the way science works. This is fabulous.

Holly Wyatt:
And I hope we get some clinical trials. Well, now it's not just about maximizing weight loss.

James Hill:
Absolutely.

Holly Wyatt:
It's about more. All right. Here's number eight for me. we never fully appreciated how much food noise people were experiencing.

James Hill:
Oh, my gosh. I think that is a huge surprise.

Holly Wyatt:
Yeah.

James Hill:
We didn't even talk about food noise before a few years ago, and now it's everywhere. And I know you and I, as we talk to people, I think this is one of the biggest benefits that people are getting from the medications.

Holly Wyatt:
Yeah. It took these medications really to, I guess, reveal how much mental space, occupied, how much mental space was being used and energy was being used in some patients.

James Hill:
Yeah, that's a big, big surprise to me.

Holly Wyatt:
And we didn't realize it until it was gone.

James Hill:
And now there's a whole field of study in food noise. And quite frankly, Holly, we're just beginning to understand it. We're just developing ways to measure it. We're now doing studies, but we know so little about it. I think some of our colleagues who study appetite regulation and so forth actually believe that reducing food noise may be one of the ways this medications are most effective.

Holly Wyatt:
Most effective.

James Hill:
Maybe one of the ways that it helps reduce weight loss.

Holly Wyatt:
Although…

James Hill:
If you think about it.

Holly Wyatt:
Yeah. But Jim, think about this. If you do decrease food noise, I would think that would translate into quality of life improvement.

James Hill:
You would think so, wouldn't you? Isn't that interesting?

Holly Wyatt:
Maybe we're asking the wrong questions. Maybe it's only in certain people. I think we need to look at that.

James Hill:
I agree.

Holly Wyatt:
But Jim, how did we miss something so important? I don't think, food noise has been there. It's not new.

James Hill:
I think because we were concentrating on other things. We were concentrating on the amount of food intake, on weight loss and everything. And I think we just dismissed that. I mean, I think we've heard before that people start talking about, well, I think about food a lot, but we didn't take it seriously until recently.

Holly Wyatt:
And until our patients got rid of it.

James Hill:
This is one where our patients made us rethink this.

Holly Wyatt:
And they said, this feels really different and I like how this feels. And so I think that was it. But I'm going to put another question. This is where I think we're going. It's like anything, we swing one way and then we swing back. I think we're going to start talking about too little food noise.

James Hill:
I agree. You and I have talked before. Food noise is not all negative. There's a part of food noise that provides important cues and feedback. And I think as we understand food noise, it's not going to be all good or bad.

Holly Wyatt:
Yeah. We dial in someone's weight. Think about this, Jim. We dial in their food noise.

James Hill:
Yeah, absolutely.

Holly Wyatt:
There's too little is not good. Too much isn't good. What's that perfect place for the food noise?

James Hill:
Amazing that we can now focus on that.

Holly Wyatt:
Yeah.

James Hill:
The number nine surprise is that so many people discontinue medications that work so well. So you and I in our career, we've totally seen people discontinue treatment when they didn't achieve the weight they wanted, right? They would drop out. “I've only achieved two or three or 4%. I'm done.” But what we're seeing are people that are wildly successful at losing weight that discontinue these medications. And the sad part is that almost all of these regain weight when they discontinue the medications.

Holly Wyatt:
And I think some of the reason may be cost and access, but I don't think that's at all. I think even if we solved or when we solved the cost and access part of this, I think more people will stay on. But I still think we're seeing kind of this idea that people don't want to stay on these medications long term.

James Hill:
Yeah, and it's interesting. I don't know if that's going to change or not. I think it's certainly the case right now. Most people we talk to have this idea where “I'm okay to use a medication to lose the weight.” But you shouldn't have to use a medication long term. You should be able to do it on your own. I don't know if that's going to change or not as we get more medications, lower doses of medications. Maybe it'll change. You and I talk to people that go on the meds and the majority of them look at using these meds for a short period of time, but they don't go into it thinking they're going to do it forever.

Holly Wyatt:
Yeah. Some people would say it's that they don't understand. We haven't educated that the medication, when you stop the medication, it's going to come back.

James Hill:
Maybe that's it. Maybe we should direct attention toward getting people to stay on them. I don't know. You and I have taken a little bit of a different approach, which is to say, if people are going to stop them, let's help people maintain with lifestyle. And it's not an either or. I think we can do both. But for right now, the majority of people who start them don't stay on them long term.

Holly Wyatt:
Yeah. And I think part of it for me is when I do talk to people and I explain that to them, they still don't want to stay on them. So even when I'm sure they understand what's going on, and I think we do need to do a better job of explaining if you go off the meds. I still think people think of these meds as jumpstarts. Just using them to get the weight off. We know that, we hear that a lot. So we need to educate around that. But even when I spend a lot of time explaining what's happening and the data of what's most likely going to happen when you stop, especially if you stop without a plan, they still don't want to stay on them.

James Hill:
But I'm okay with that. And in long term, I would love a world where people could use these to lose weight and keep it off with lifestyle. Unfortunately, I don't think we're there yet. So as you look at the future, I'm okay with efforts to get people to stay on longer. But I think we also need efforts to help people maintain without the medications and keep the weight off. It's not an either or. It's both paths we should pursue.

Holly Wyatt:
And I think one key, and I've been thinking about this more, is a lot of times when we stop a med, it's an immediate, you know, within the half-life of the med, and then the blood pressure goes up immediately or in a few days or weeks. Not the same with weight. There is more of a delay that the time course is different.

James Hill:
Right.

Holly Wyatt:
All right, Jim, are we ready for the last surprise?

James Hill:
Last one.

Holly Wyatt:
All right.

Holly Wyatt:
Surprise is one medication can have an astonishing range of therapeutic applications. So what I'm talking about, here's the GLP-1s. They started out as a diabetes treatment, and then it expanded into obesity. And that's normal. A lot of times, not normal, but that made more sense to me. We saw weight loss in the diabetes trials, and so it expanded into obesity. But now it's even just expanding everywhere. There's multiple other approved or investigational indications, you know, cardiovascular, kidney effects, liver effects, sleep apnea. We're studying the cancer, Alzheimer's, studying the addiction type behaviors. My goodness, one therapeutic, you know, one medicine with so many different therapeutic applications. That's surprising to me.

James Hill:
It's totally surprising to me. And again, we haven't seen major negative metabolic effects. And that's surprising, too, that pretty much everywhere we look, it's a positive effect.

Holly Wyatt:
I mean, these receptors are a lot of places. Having a lot of impact on the body, potentially. Yeah, so it's surprising that. And yeah, they seem to be positive at this point.

James Hill:
So, wow, Holly, 10 surprises. And there were a lot of surprises in there. So we've spent decades trying to figure out how to help people lose more weight. I'm excited now that we are finally discovering that weight's not the only outcome. And we're asking some better questions, I think. And again, before we could produce this weight loss, nobody could get past weight loss. Now we're getting past weight loss because, again, I think very soon we're going to have a treatment that will help people, most people, reach their weight loss goals. Now we get to ask a whole bunch of different questions, and that's exciting.

Holly Wyatt:
One of the questions that I think is the most important for the field is, I think, finally, we're getting to ask, is successful weight loss is different than successful obesity treatment?

James Hill:
Yes.

Holly Wyatt:
We're finally getting to not confuse that, right? That weight loss, successful weight loss is different than the whole package of obesity, successful obesity treatment.

James Hill:
Yeah. And part of it is when a treatment comes along, we want to say, “Oh, this is it. The medications are it. They've solved everything.” Well, the medications are game changers for weight loss, but they haven't solved everything. And the medications alone aren't the answer. They're part of the answer. But prescribing a medication is not prescribing a comprehensive obesity treatment plan. And we need to better define what those comprehensive plans are.

Holly Wyatt:
Do you think that we have underestimated the complexity of obesity treatment?

James Hill:
Well, I think some people have. I don't think you and I have, because we've seen this for years and years and years. This is so complex. We don't even totally understand why obesity develops, Holly. So it is so, so complex. And everybody differs. Everybody differs in how and why they develop it, what the consequences are.

James Hill:
This is a complex problem.

Holly Wyatt:
So, Jim, let's spend the last part of this podcast. I thought it would be cool to talk about what don't we know yet? We've learned things from these medications, but maybe what our current assumptions will turn out to be wrong. Like what would we be surprised about in the future yet to come?

James Hill:
Yeah, I guess one of the things I think about a lot is prevention. We constantly say ultimately we want to prevent obesity. And my question is, are these medications and effective treatment, are they going to help or hurt efforts to prevent obesity? On one hand, you might say, well, at the first indication of a metabolic problem, boom, you give the meds. So you don't develop these things because of the medications. On the other hand, you could say, well, wow, the success of these medications, everybody losing weight may want people to say, oh, we've got to go back and help people not gain weight. So I think it could go either way. But I think this is a big, big question for society.

Holly Wyatt:
Yeah. I also think about what happens over decades.

James Hill:
Yeah.

Holly Wyatt:
We could be surprised or there could be some assumptions that turn out to be wrong about long-term treatment.

James Hill:
We know very little about people that are staying on these medications for three, four, five years, which is about as long as we have. We know nothing about people that are on them for 20 and 30 and 40 years. Maybe everything is wonderful, but I think we've got to look at the long-term effects.

Holly Wyatt:
And the potential for weight cycling.

James Hill:
Yeah, that's what we worry about. We're seeing it already. People stop the meds, they regain a little, they go back on it, they try lower, I mean, people are trying everything. And, you know, we will hopefully figure out some of this.

Holly Wyatt:
Yeah, I worry about the weight cycling, Jim, just because I do want to understand what it's doing to body composition. Just because we've seen it before and we know that you can change. You can weigh the same amount, but change that composition, and especially maybe in a certain population.

James Hill:
You could be doing a negative effect on the population if people go through these weight cycles.

Holly Wyatt:
Exactly.

James Hill:
The other thing, too, is what else are we missing? We miss food noise, right? Huge, huge deal. And we missed it. Are there other things out there? Big things that we haven't discovered yet or we have missed?

Holly Wyatt:
Yeah. And that's, I guess, that's the part of science I love. We figure something out and it usually produces more questions and we get things wrong.

James Hill:
And now that we're concentrating, hopefully concentrating on outcomes other than weight, maybe we're going to see some of this. Maybe we're going to find other things like food noise that are just, “Oh, wow. Had no idea this was important.”

Holly Wyatt:
Yeah. So, Jim, I've been thinking about this last question. I don't know if you have. So I can go first. But, you know, of everything we've talked about today, what do you think will surprise us most, 5 years, 10 years from now?

James Hill:
Well, what I think is we've got these wonderful medications, very powerful. I think we may look back and think maybe we didn't introduce them to the population in the right way. Maybe there would have been a better way of preparing people for them. For example, you and I talk to a lot of health care professionals that aren't obesity experts, and they're prescribing the drugs, but they have very little information about diet and exercise and other things. So maybe we look back and say these powerful tools could have been introduced to the population more effectively. Now, it's easy to go back and criticize in the past, but thinking about things… I understand that the drug companies wanted to get these out because they were wonderful tools. They were going to make a lot of money. Totally understand that. I just wonder if maybe we should have thought a little bit more about how people are going to use them, how healthcare professionals are going to use them, et cetera.

Holly Wyatt:
So I was thinking about this and I was really thinking about the food noise, how this was totally kind of a surprise for us and we hadn't even talked about it. So I came up with, I think we might be surprised. We may discover that, people don't need the meds forever. That there may be, you know, we think about chronic and you need to be on the meds forever. And we make it seem like a blood pressure pill or a diabetes medication. And I understand why. And I do think you need chronic treatment. But the idea that we won't use medications in that same way, we'll maybe use them more episodically, or that there will be a population or subgroup of patients that we can identify that don't need to be on them forever. And that's very different than how we think about it today. But I think that could be something that surprises us in the future, that it's more personalized and episodic and not for everybody, that they have to stay on the med.

James Hill:
Wow, Holly, we've covered a lot of good stuff in this episode.

Holly Wyatt:
Yeah, it was a good one. The one more thing I want to add, because I thought a lot about this, is I think these meds may surprise us in that they're changing what motivates us.

James Hill:
Hmm. Interesting.

Holly Wyatt:
Because we know it's impacting the reward system, right?

James Hill:
That's right.

Holly Wyatt:
So it may be helping for certain behaviors around alcohol and other things, but it's changing that system. So I think we're going to be thinking about that a little bit more.

James Hill:
There could be some negative effects of hitting those reward systems. We're already in social media, they're talking about a Ozempic mood.

Holly Wyatt:
Yes. And so it impacts what people want to eat, but it also may impact what they enjoy and how they want to pursue their life and, you know.

James Hill:
Absolutely. Absolutely. Okay.

Holly Wyatt:
All right, Jim, take us home.

James Hill:
Well, we finally have medications that can produce weight loss we once thought were impossible without surgery. But now that we're here, we see a whole bunch of additional questions that we need to ask. People can produce weight loss, but the data suggests they're not improving their quality of life. They're not eating better. They're not going out and exercising more. So we've got part of the problem solved, but we still have some challenges. And then in my mind, the biggest challenge is long-term. We now have the weight loss part solved or pretty much solved, but we don't yet have the keeping it off solved. And that's our biggest challenge in the future.

Holly Wyatt:
Which I think means we have a lot of science ahead of us and probably a lot more surprises too.

James Hill:
But what a great time for obesity treatment. And the good news is we have more effective treatments than we've ever had. The science is moving quick. There are going to be more options. So there's a real reason to be optimistic for the future.

Holly Wyatt:
Yeah, and if you're listening and you have something that surprised you, send it to us. Let us know what's surprising you.

James Hill:
We want to hear from you. Thanks, everybody. And we'll see you next time on Weight Loss And.

Holly Wyatt:
Yes, bye.

James Hill:
And that's a wrap for today's episode of Weight Loss And. We hope you enjoy diving into the world of weight loss with us.

Holly Wyatt:
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James Hill:
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Holly Wyatt:
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