The Science and Realities of Long-Term GLP-1 Use

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:
Today, we're talking about something that almost nobody prepares people for when they start a GLP-1 medication. Not how the weight loss starts. We talk a lot about that. But what happens after the weight loss slows down? Or what happens when it stops completely? Because eventually, almost everyone on these medications reaches the same moment. The scale stops moving. The excitement changes. People start wondering, is the medication working? Did it stop working? Did my metabolism adapt? Why does this suddenly feel different?

James Hill:
Yeah, Holly, I think this may be one of the biggest misunderstandings in obesity treatment right now. If the medications work well, you will reach a plateau. You will lose weight. But fortunately, you don't keep losing weight forever. You would waste away to nothing. So people think that the slowing of weight loss and reaching a plateau means something's wrong, but in fact, it's totally expected.

Holly Wyatt:
Absolutely. That's exactly right. And today we want to unpack the difference between losing weight on GLP-1s and maintaining your weight on GLP-1s because they're not the same physiological state. And once people understand that, I think the whole conversation starts to change.

James Hill:
Yeah, Holly, it comes back to something you and I have been sort of saying for really decades, that weight loss maintenance is different than weight loss in lifestyle treatment, obviously the case, but even in medication use, you have to think about keeping the weight off differently than losing the weight. So on the first wave of GLP prescriptions, the conversations, do the drugs work? Holly, we know they work. We have seen amazing weight loss. Now the questions are changing.

Holly Wyatt:
I agree. We focused on do these things really work? And, you know, almost not believing that. And I think people now say they do work and people aren't questioning that, but they're starting to ask things like, well, and I'm really happy about this. What happens long-term? Finally, you know, people are thinking about this, not just a short-term weight loss. What happens when my weight loss stops? And we call that a plateau. Can I stay healthy eating this little? I love that question because for a lot of people, they're not eating very much at all. And what do we do about that? Can I lower the dose? What happens to my muscle? Those are all the new questions that are coming up.

James Hill:
I think we understand the weight loss, not totally, but we understand it pretty well. We know that these medications help you feel satisfied on far less food and that reduction in food intake can produce substantial weight loss. What about maintenance? This is where there are some unanswered questions. And Holly, one of the things I know, one of our listeners actually felt like you and I didn't really condone long-term medication use. Is that true? Are we against long-term medication use?

Holly Wyatt:
Yeah, I love that our listeners are writing in and telling us their stories. And this was someone who wrote in and said, you know, I've been on a medication for years and it's changed everything and it's working great in maintenance. And they'd listened to all of our episodes, but they also said it was, it's very obvious to me that you do not agree with being on these medications long term. And that kind of broke my heart a little bit because I was like, oh, our message is not getting out there clearly. Because I do believe in these medications long-term for people that want to stay on them long-term or some combination of behavior and being on the medication, or not being on the medication. I believe it's about picking what works for you in that situation, not one being the right choice or, you know, not believing in medications long-term.

James Hill:
Yeah. You and I know lots of people that are on the medications. They've been on them long-term and they love it. And what we're saying is great, but not everybody feels that way. And so again, we've been looking at providing tools and strategies that match the individual. Some people go on the meds, they love it, they tolerate the side effects, da-da-da. Others don't. They may not lose the weight, they may not enjoy it. There are different options for different people.

Holly Wyatt:
Exactly. I think because we've maybe questioned, what happens in maintenance and we talk about even the questions that we're going to talk about today may then make it seem like we're against the medications long term because we bring up some of the things to think about. But I think for some individuals, and this individual seems very, very successful long-term, doing really well. And that's a success story. And I am 100% behind if that's the right journey for them. And it sounds like it is. That's good.

James Hill:
So we've declared on the record, Holly, we are not against long-term medication use. If that works for you, we're all for it.

Holly Wyatt:
And I would even say we support it if it's making sense for that individual.

James Hill:
But we will talk in this episode about maybe there's some other things that you may need to do, even if the medications are working long term to optimize your health. So let's start with this one. Why does weight loss slow down on the meds? Why don't you just keep losing weight?

Holly Wyatt:
Yeah. So we understand that. I think people don't understand the physiology that's involved in a weight loss. It's normal, and I would say thank goodness that you eventually stop losing weight because you would die eventually if you just kept losing weight forever. So these medications have a certain efficacy and effectiveness, and they produce a certain amount of weight loss in an individual, and then that weight loss stops, and that's completely normal.

James Hill:
As you lose weight and you have a smaller body, Holly, that body needs less energy to maintain it. And so you've got this gap when you start reducing food intake, your energy expenditure is higher than your food intake. But as your body adjusts, as it becomes lower, that energy expenditure comes down. And finally, you reach a stage where your energy intake and expenditure are equal again. And that's when body weight plateaus.

Holly Wyatt:
And that's expected. That's normal. I think one thing to realize is for a lot of people, unless they're putting in a lot of exercise or moving more, that new balance where intake is equal to expenditure is probably at a lower level than it was.

James Hill:
Right. That's right. And that's one of the problems for when you stop the medication because your energy expenditure is so low, you're in this situation where you're going to regain weight very quickly if your food intake rises.

Holly Wyatt:
So plateaus, meaning you've had some effect, you've lost some weight over time, and then the weight loss slows down. Usually it slows down. You might've been losing two pounds a week. Maybe now you're losing one pound, then it goes down to a half pound. And then eventually, it stops. That is normal. That doesn't mean the drug isn't working. And that's what a lot of people think. Oh, the drug has stopped working because my weight loss has stopped.

James Hill:
And the good news is for most people, that only occurs after significant weight loss. So in most cases, you've lost a lot of weight by the time you reach a new plateau. But that plateau is when you change from losing weight to keeping it off.

Holly Wyatt:
Right.

James Hill:
And what do we know about long-term use of these medications to keep weight off?

Holly Wyatt:
They work if you keep taking the medication for most people.

James Hill:
So even though your weight isn't changing, the medication is still working, right?

Holly Wyatt:
Exactly. The weight has stabilized and that's expected. And sometimes I have people think of it like a blood pressure pill. If someone goes on a blood pressure pill, it will reduce their blood pressure, their systolic, their top number, their bottom number, their diastolic by so many millimeters of mercury. It will only go down so much. And then that's the effect or the impact that that medication has on their blood pressure. Same thing with these drugs. That's the impact these drugs have on their weight and it will stop. And then if you stay on the blood pressure medication, you stay, you know, at that lower level of blood pressure. Same thing with the weight loss medications. You stay at that lower level of weight, that new equilibrium. What I think people sometimes say, and they're using these words interchangeably, is it's resistance. I'm now resistant to the drug, Jim.

James Hill:
But you're not because the drug is still reducing your food intake. It's still working exactly the way it's supposed to work. Now your body has adjusted and reduced energy expenditure. So you've reached a new equilibrium at a lower body weight. And this is a good thing.

Holly Wyatt:
Right. So if you had lost responsiveness to the drug, if for some reason your body now wasn't responding, You would expect perhaps the appetite to come back big time.

James Hill:
Right.

Holly Wyatt:
You would expect the food noise to be coming back full strength. You would expect to start seeing some weight regain. Now, sometimes ehaviors, other things can change and you can have some small changes in weight. So it's not a hundred percent. But if you're starting to regain on the drug, that may be a little bit different than if you're maintaining on the drug.

James Hill:
But from everything we know, you take the drug, you lose weight, you feel good on the drug, you keep taking it. The drug helps you keep the weight off.

Holly Wyatt:
[11:07] And I'm just going to point this out because I don't, I Google or I look up the wrong thing and then my social media feeds are filled with things. And one of the things I'm seeing right now is everybody's like, “Oh, you stopped losing weight? Change where you give your injection.” They're like, “Oh, it's because you've given your,” and I have seen no data. And I've talked to multiple people that are out there treating a lot of people with these drugs. I've talked to the pharmaceutical companies. I don't know of any data that says, you know, you need to change or go to injecting in your leg or your arm versus your abdomen in terms of that being the reason that your weight loss is slowing or that your weight loss has stopped. So that's the problem we have, Jim.

James Hill:
We don't have the science, so people are making it up.

Holly Wyatt:
Yeah, and maybe one person switched their site and then they also did something else like increase their physical activity or change something else and weight loss started again a little bit for them. So they really believe that worked and we did a whole show on that. When one person has success, then they want to tell everybody about it and how to deal with that. But this is really getting to the big problem. We have so many people on these drugs. They're reaching these plateaus. They're going into maintenance. And the science has not caught up.

James Hill:
So what do we know about diet? So we've done some podcasts where we talk about, while you're losing weight because you're eating maybe a third fewer calories than you did before, you're going to lose weight, but you have to worry about getting enough protein and vitamins and everything. Is that different doing weight maintenance? Do we know how nutrition should differ between weight loss and weight loss maintenance on the meds?

Holly Wyatt:
I don't know that we know for sure. You know, we're given advice, the best advice we can give based on what we know. But one thing I want the listeners to think about, because this has come up now several times for me, people come to me and say, oh, for the first time, I don't have to think about what I'm eating. For the first time, that food noise is gone. So it's like, “I used to have to think about everything I was putting in my mouth. I used to have to write it down and log my food. And for the first time, I'm so happy, Holly, that I don't have to do that. I don't have to think about what I'm putting in my mouth.” And I get it. For the first time in their life, this food noise is gone and they've had to deal with it for so long. But I'm gonna challenge people to say, I now think when you go into maintenance, because maintenance is the forever, maintenance is the years, Maintenance is where if you don't have good nutrition, you're going to start to see effects over time. You may have to think more. Nutrition may be harder. You may have to log your food when it comes to this, even though I know that's not what people want to hear. I think in maintenance on these drugs, nutrition doesn't go away. Nutrition becomes more important.

James Hill:
The drugs are working by reducing your food intake. So you're still in the situation where you have a lower food intake, but you still have to get adequate nutrition. So in some ways, during maintenance, you have to be a little more careful with the quality of the food you eat because you're eating less than you're used to.

Holly Wyatt:
So I have people that are now having to log their grams of protein and are having to think about what they're going to eat first. They want to be able to have some dessert. And I'm like, well, before you have dessert and get full on the dessert, we want to make sure you have, a basic amount of the micronutrients we need and the protein we need and the calcium and the vitamin D and all of that. Are you getting what you need? And why I think it's even more important in maintenance and weight loss. It's important in weight loss. We need to deal with it in weight loss. But in maintenance, to me, it becomes even more important because this is forever. This is long term. This is where major health is going to be determined, what you eat for a really long period of time.

James Hill:
And one of the things that maybe we'll go to a little bit later is because maintenance forever, this is where you need to get your routines and everything down because you're going to do them forever. And I know, Holly, we've talked before about the importance of working with people that know nutrition and working with a registered dietitian during weight loss maintenance can help you figure out a pattern that hopefully can become routine for you really forever.

Holly Wyatt:
Right. And I think the routines and the patterns important because the food noise is gone, you're going to have to think about food. You may not naturally think about food. The food noise served a purpose, even though I know people didn't like it. It served a purpose to make you think about food and stop and eat and do those things. And now for some people, it's completely gone. So if it is completely gone, if that physiology is gone that's natural in your system, you are going to have to do it a different way because you can't rely on your body to push you to do it. You're going to have to do it.

James Hill:
So our message is nutrition and what you eat is critically important for weight loss maintenance. If you're on the meds, obviously without the meds, but on the meds, it's still very important.

Holly Wyatt:
I think it's even harder. It's even more.

James Hill:
You've got to get a good quality of intake on a lower, absolute lower food intake.

Holly Wyatt:
And with no appetite or food noise to help you in that sense.

James Hill:
All right. We hear so much about lean body mass with the GLP-1 medications. And a lot of people are saying, well, we worry that we're losing too much lean body mass during weight loss. and there are recommendations around eating more protein and more resistant to exercise. How does that flow into maintenance? How do we think about lean mass differently or muscle differently in maintenance?

Holly Wyatt:
Well, I think once again, it's the amount of muscle you're going to have to live your life forever. It becomes related to more than just the weight loss. You know, people want to live life and function well. And so we now are thinking about muscle, not just in the amount, but the functionality of it. I think it's important in weight loss because that's when you may lose it. But in maintenance, you want to also be thinking about that.

James Hill:
So protein, probably protein intake and resistance training become critically important in maintenance and being able to do this long term, right? We're talking forever. So we're talking about these routines and habits that are important. And the requirement for protein and exercise doesn't go away. What you want to do is to not lose more lean body mass, to maintain what you have. And higher protein and resistance training is probably still a pretty good strategy for maintenance.

Holly Wyatt:
Yeah, I do want to say we don't have great data on this, Jim.

James Hill:
That's exactly right. I mean, we're doing our best guess here because we haven't really studied long-term weight loss maintenance on these medications. What is long-term here. So you can think about, well, a year, two years, three years, four years, we're telling people they may be on these medications for 20 and 30 and 40 years. So we are going to really, over time, need some more long-term data to really be able to advise people in the best way.

Holly Wyatt:
And I think it was Ken Fujioka who talked about even that cycling that may be occurring on the drug. So there may be periods of time when you're in maintenance, you regain some, you might go back on the drug, lose again. That may be even a different scenario than losing and maintaining. So we just don't know. I think some of the beginning early data that's come out that says it may not be as big a problem as we think it could be, but we still don't have all the data we need. I think for me, there could be subsets within the population where it is going to be a problem and maybe subsets where it's less of a problem, certain populations. I think we're just starting to understand it may not be the amount, it may be the functionality of that muscle that's really important. So how do we test for that? Are we testing for that? How do we look for that over time? It's very similar to bone. When we first started getting, you know, DEXA and looking at bone, we would look at density of the bone. And then we said, whoa, whoa, whoa, it's not really just about the density, it's really about fracture rates. And that changed the field. I'm not a bone expert, but we changed how we started thinking about it. And I think muscle, we're going down that same path. It may not just be the amount of muscle or lean tissue. It may be more how it functions over time.

James Hill:
It's really created a lot of new, interesting research around not just amount of muscle, but muscle function.

Holly Wyatt:
Yeah.

James Hill:
All right, Holly, we've always said that physical activity, while it's helpful in weight loss, is critical in weight loss maintenance. Does that change if you're maintaining weight on the drugs?

Holly Wyatt:
Oh, that's a hard question because I want to say it matters whether you're on the drug, off the drug, whether you're maintaining or not. But the truth of the matter is you can be successful maintaining a weight loss on the GLP-1s without increasing your physical activity. I think there are people who are doing this. I think there's people who have increased their physical activity, but I think there are people who are maintaining their weight on a GLP-1 and have not increased their physical activity. So this is where people may misunderstand what we say a little bit, because I believe you really do need to increase your physical activity for things more than just the weight. But let's be honest, you know.

James Hill:
You and I are big fans of physical activity, and I think we want to believe that it's absolutely critical. But at the same time, you and I are bound by the science and we just don't have enough science. Here's what I would say. I actually think we're probably going to find that it does matter, but it's still an open question. One of the things that we talk about that physical activity does is to strengthen your metabolism in general, to give you metabolic flexibility. And with the meds lowering food intake, you may not need that, but I just see physical activity as optimizing your metabolism in many, many ways. And even though the meds maintain the weight loss, I still think having a flexible metabolism is going to be better for your overall health. Then the other thing, I think the psychological and mental health benefits of exercise are often under recognized. And I think that is going to be critical in the long run, too. So we desperately need more indications here. It's very clear you don't have to exercise to keep the weight off. But I think exercise is going to enrich your health and quality of life in other ways beyond just keeping the weight off.

Holly Wyatt:
Yeah. Just like we talked about nutrition and becoming more important, and perhaps you even have to spend a little bit more time on nutrition and weight loss maintenance on the GLP-1s. I think you're going to maybe have to spend a little bit more time and think about the physical activity, too, because you don't have to do it to succeed.

James Hill:
Right.

Holly Wyatt:
So you've really got to think about the other reasons because you could be successful without it. But is that, you know, I think it comes down to what the definition of success. Is it just about keeping the weight off or is really what you're going for bigger than that?

James Hill:
Yeah. So, again, the jury's out. I want to believe that physical activity is going to turn out to be very, very important in weight loss maintenance but the science hasn't caught up yet. I do believe that it's going to enrich your health and happiness being physically active. And I hope we get more research to actually be able to quantify the impact of physical activity over the long term.

Holly Wyatt:
That's true, Jim. We have really good numbers about how much physical activity on average is required for people to maintain a weight loss not on the medications. But we don't have any real data to say what would increase your odds on the GLP-1. That may be a different number.

James Hill:
And things like if you're physically active, does that make you more adherent to medication? There's just so much we don't know and so many ways that I think physical activity could play a supportive role in people on the meds long term.

Holly Wyatt:
I agree. So it sounds like we're getting quite a long list of things we don't know. All right, here's another one, Jim. Bone health. We talked about muscle.

James Hill:
Yeah, boy.

Holly Wyatt:
Bone.

James Hill:
We've had a couple of guests on here that I hadn't recognized what a potential problem bone loss is, and particularly in vulnerable groups, young women who are building bone density, losing weight and losing bone density at a time where they're never going to recover it is a little bit scary. People have recognized loss of muscle, but I don't know that people quite recognize the importance of not losing bone density as you lose weight.

Holly Wyatt:
You know, we focus maybe on an older population about the muscle loss and that might being a population that we really need to look at in terms of the muscle loss.

James Hill:
It is, that's right.

Holly Wyatt:
And then it may be a younger population we need to focus intently on looking at bone loss a period of time where you may not be able to get it back and you don't want to miss that window.

James Hill:
I don't think we know yet what we can do to minimize that. But, you know, people are talking about calcium, vitamin D, other kinds of things. But there's just no information about strategies to reduce bone loss in those young women on meds.

Holly Wyatt:
So, Jim, you know, I'm an endocrinologist, so I should know my bone really, really well. And I did take the, you have to take the board every 10 years. So I redid my board and I passed. But I will say that bone was my weakest area. So I think we need an expert in bone to help with this a little bit more. I also will say I think bone was my weakest area because in the past with obesity, you had strong bones. I was not seeing people that I needed to treat osteoporosis for. I was really good at treating diabetes. I'm really good at treating lipids. I'm really good at treating all the metabolic, you know, all the metabolism stuff associated with obesity. But bone and osteoporosis was not associated. So that's not my area of expertise.

James Hill:
But bone health is something that should be carefully monitored in particularly younger women who are taking these medications.

Holly Wyatt:
I think that the GLP-1, these medications may change that. We may have to start looking at bone, and it's not something we looked at in terms of obesity treatment very much in the past.

James Hill:
Okay, Holly, I've got one for you that I don't know the answer to. We just talked about the fact that if you're on main, that you stop losing weight. The drugs are working, you're still eating less. Does appetite change at all when you switch from weight loss to weight loss maintenance? You're still eating less, but are you eating the same amount of less or does that change?

Holly Wyatt:
Right. I don't think we know. There's very little data on looking at appetite over time, like looking at that kind of the trajectory data. I think it's a great question. That's what kind of gets people into the difference of plateau where I'm becoming resistant. You know, so is appetite coming back? Is that what's driving if the weight's coming back or, you know, is the weight staying the same, but you still feel like the appetite's coming back and you're fighting it? And I just don't think we know really what's happening.

James Hill:
Does your appetite stay the same over decades if you're on the medication?

Holly Wyatt:
Yeah. I, you know, and it would make sense. There would be some drift, not because the medication's not working, but life changes. And we know appetite changes over your lifetime.

James Hill:
And we know nothing about preferences and cravings and all that. Is that different when you're losing weight versus when you're maintaining weight? There's just so much to learn about long-term weight loss maintenance on the medications.

Holly Wyatt:
Right. I don't know the answer to that question either. I think we need to really be looking at that. And appetite can be hard. I mean, there's ways we look at appetite, but it's sometimes hard to be able to follow over time. It can be a little bit subjective. And so it's a harder thing, but we don't have anything. We just got something that measures food noise. So we're trying to catch up.

James Hill:
We're catching up. Okay, Holly, this is one where we get questions all the time, and every clinician we've talked to gets these questions over time. Can I reduce my dose? Can I taper? Can I go down to a very low dose long term rather than continue at a higher dose? What do we know?

Holly Wyatt:
That it's the wild, wild west out there.

James Hill:
It really is, isn't it?

Holly Wyatt:
It really is. And I feel bad because we have lots of people on these medications. And I don't think we have good information for them to say for sure what to do. Obviously, some people are backing off on the dose or spreading out how often they give the injectable. We have great data that if you stop, what happens in the pharmaceutical trials? If you stop altogether, weight regain happens, unless you have another plan, unless you do something else. That's more likely what will happen at that point. But in terms of how to change the dose or what to do, I don't have good data.

James Hill:
You and I have had some really terrific weight loss docs on this show, and without any science, they're working with people trying different things. Obviously, they're watching it very carefully, and they would love to have the science to do it. But people are demanding these sorts of things anyway. And the fact of the matter is, you can get a dose and use part of it and not use part of it. And the person has some ability to modify that. So it is happening. We just have not captured what works, what doesn't work, what to be careful with. It is the Wild West.

Holly Wyatt:
Right. So this is where we need to be capturing what the clinicians that are in the real world are doing and what is working. We need to be capturing that data to really inform the science. So I think people are trying to do that. You know, there are some pharmaceutical studies that are coming out looking at this question. You can decrease the dose. You can change the dose. You can change how long, you know, instead of every seven days, you do it every 10 days or you do it every, you know, two weeks. They're looking at that. Something that they're starting to study, and Jim, I think you're going to like this. This really sits well with me, is you may change medications, meaning there may be certain medications that are really good at restricting intake, getting the weight off, and maybe they have some stronger GI side effects. You might be able to switch to a different medication to keep it off. And so there's trials right now looking specifically at transitioning to a new medication for weight loss maintenance. And then there's been some studies that have recently come out looking at maybe you change from an injectable to an oral. And that might work better for getting the weight off and then keeping it off. And what I love about this is for the first time, people are starting to say, “Oh, wow, what works best for weight loss may not be what works best for weight loss maintenance.”

James Hill:
Finally, Holly, after decades of saying that.

Holly Wyatt:
I mean, they're like, wow. And I'm like, oh, come on. This has been out there. But I love that we're starting to see that make sense.

James Hill:
You know, all that is really exciting because it's like almost unlimited options. The problem is studying it scientifically so a clinician can look at a patient and make the best guess on what kind of strategy is going to work for that person.

Holly Wyatt:
The other thing to add into this discussion about can you lower the dose and maintain or how do you lower the dose and maintain is that you're, you know, that's talking about kind of the biology of it, but behaviorally things change over time too, Jim. You move, your environment changes, you retire, you get married, you know, things change in your environment and that changes your behaviors. And that changes how much of the med you may need or what you can do with the medication.

James Hill:
Absolutely.

Holly Wyatt:
It's complex like that. It's not just one thing that's changing over time.

James Hill:
Lots of opportunities for research, Holly, in maintenance. And fortunately, people are starting to look at that. I mean, I couldn't be happier. Everybody wanted to study weight loss for many, many years. And now people are saying, hey, we need to study weight loss maintenance. So I welcome that.

Holly Wyatt:
I hope that the listeners start to embrace that. Some of them still aren't yet. It's still about the weight loss really thinking about what do you want your life to be? What do you want to be doing? How do you want to be living in that weight loss maintenance in that smaller body? How do you want that to feel? And starting to personalize that about what will work for them and really what they want.

James Hill:
Switching gears a little bit. Almost every day in the news, I see another positive effect of the GLP-1 medications. They reduce cardiovascular disease, fatty liver, sleep apnea, kidney disease, osteoarthritis, maybe even cancer. And it's amazing what these are doing. Now, we don't know why they're doing it. Is it the medication? Is it the weight loss? Is the reduction in food intake? But some combination seems to have amazing improvements in overall metabolic health. Do we know if those persist during weight loss maintenance where weight isn't changing anymore?

Holly Wyatt:
Ah, that is a good question. And Jim, just recently, a couple days ago, and we're going to need to do a whole episode on it, there was a, I think, a Cleveland Clinic analysis that showed decreased progression of metastatic cancer and, you know, several different kinds of cancers, meaning decreased metastatic disease, which is huge. And so it's really coming, what's going on here? It was an observational study. These tend to be observational studies, so we can't say they're causation. There just seems to be this observed relationship that's there. But this is the hot topic. And I think you're right. Is it the GLP-1 medication? And a lot of times there are receptors on these cells. So it could be. Or is it simply you're eating less? Is it simply you've lost weight and insulin resistance and all of those markers have changed? Inflammation has changed. Your immune system has changed. I mean, what's going on? But you're right. The list gets longer and longer in terms of these associations we're seeing between the GLP-1 medications and improvements in things in almost every body system.

James Hill:
Holly, there was just a really fascinating article, I think it was in the New York Times, about how these medications are rewiring our brains. And they were talking about the potential long-term consequences of that, both good and bad. And there was a statement in there of like, we are doing the biggest neurological experiment in history.

Holly Wyatt:
All right, that scares me. I don't like this rewiring brain thing, Jim.

James Hill:
Well, I don't know. If it is rewiring the brain, we need to understand the positive versus negative. And this article was good. It was sort of talking about how that could be a good thing. Was also talking about maybe there could be some downsides. But the way that these medications have changed every aspect of what we're looking at metabolically in the body is amazing. And are we having a whole bunch of people that now have rewired brains? And is that a good thing?

Holly Wyatt:
But that plays into the maintenance. So once you rewire your brain, is it rewired forever? Or does it un-rewire when you stop the meds? I mean, I wouldn't think it would un-rewire, but maybe it does.

James Hill:
Great question that we don't know the answer to.

Holly Wyatt:
I don't know about this rewiring of the brain, Jim. That makes me uneasy just because...

James Hill:
Well, we need to think about it. These are the kinds of things we need to think about. And you know what it suggests is, you know, it was just the obesity people that started looking at the meds, then the metabolic people, now the brain people. It's like experts from every area are coming in to look at this. And I think we're going to learn so much from all this.

Holly Wyatt:
Yeah, that's good. I think the more people looking at it from different areas, the more we're going to understand how it works.

James Hill:
But Holly, you would have to say, overall, taking everything we know, it's much more positive than negative.

Holly Wyatt:
I agree. I agree. But I want to look up how it's rewiring the brain.

James Hill:
Well, I'll send you the article. You can read it. All right. Here's one thing that you and I talk a lot about is motivation. And, you know, in weight loss, there is so much external motivation, especially with the GLP-1 meds where you're losing weight quickly. It's like, oh my God, Holly, what have you done? You look great. You look wonderful. Now you're in maintenance where the goal is to stay exactly the same and not change. How does motivation change in weight loss and weight loss maintenance.

Holly Wyatt:
Well, I think that's why you're seeing people stop the medication. When they're losing weight, they're motivated to still take the medication. And then a lot of times then when the weight loss stops, sometimes they think they can do it without it. And sometimes they're like, well, I don't, you know, I don't need this anymore. And the motivation to take the medication changes. I think you have to switch your motivation. You have to recognize that we're wired to see change. We love to see change. We need to thought, what is going to be motivating now that the scale is going to say exactly the same? I used to always say there's no TV show that you can get on the scale and everybody claps and, you know, you win the prize when your weight hasn't changed. That doesn't make for good TV. Why? Because people, that's not exciting to people.

James Hill:
So are you saying people need a good mind state, Holly, to stay motivated long term?

Holly Wyatt:
And I think it becomes looking for other things that are changing in your life, not just the scale. So broadening this definition of success. And that's why in maintenance, I think it's not just about the weight. It has to be bigger than just the weight.

James Hill:
And I think it's a wonderful time because the weight is so powerful and so positive. It's a wonderful time to look at other aspects of your life. You know, what are your goals? And most people, their goals are not just a number on the scale. It's closer with friends and family and more in tuned with who you are, your identity. So I think maintenance can be a wonderful time where the meds are doing the lifting on keeping the weight off. Now let's work on other aspects, on your mind state, on your physical activity, on your mental health. Wonderful time to do that.

Holly Wyatt:
This is perfect to talk about. People think once they lose the weight, they've checked the box, it's over. That doesn't work. That's why you've got to move into the second phase. And this is weight loss maintenance. And this phase is different than the weight loss phase. And motivation is different.

James Hill:
You and I talk a lot about during weight loss maintenance, you have to make it as easy as possible. And you have to look at things like your environment, your physical environment, your social environment, your routines, your rituals. Most of our behavior is automatic. We don't think about it. So it's like even on the GLP-1 meds, in maintenance, you have to have a whole new set of routines and habits that help you do the right stuff rather than the wrong stuff. And that's the thing that's important. That's not so important during weight loss. You just go and do anything for a period of time. But during weight loss maintenance, it's forever. You have to get that automatic behavior the right way.

Holly Wyatt:
Our state-of-slimmers know this. We talk about decreasing friction. In weight loss maintenance, you want it to be as easy as possible. You want to get rid of friction. That means changing your environment. That means new routines and rituals. And here's the other thing, and people aren't going to want to hear this because I know this from my state-of-slimmers. They're like, “When is it going to be over? Or when is it going to be easy? I've already changed all my routines and rituals. I've set up my environment. Am I finished.” No, you're never finished. Weight loss maintenance keeps going. Your life changes. You change your environment again, right? You move, things happen. You've got to go back in and be constantly working on your environment. Your routines and rituals change as your life changes, as you change. So it's a constant process. You're never done. And I know people don't want to hear that, but it's true.

James Hill:
Wow. All right, Holly, we've gone over a little bit. What do you want to take a listener question? You want to do vulnerability?

Holly Wyatt:
Let's take a couple quick listener questions. Do you have some in front of you?

James Hill:
I'll do this one. My doctor told me to start strength training on a GLP-1, but honestly, I thought these medications made exercise less important. Was I misunderstanding this? No, because what you need to focus on is minimizing the loss of muscle. And that's where resistance training can help during weight loss. And again, our best strategy is increase your protein, which you need to do anyway. Do some resistance exercise, which seems to help minimize the loss of muscle mass. And that's going to help you long-term.

Holly Wyatt:
So I think the question was, he was saying, am I, am I, I'm assuming it's a he, I don't know. Was I misunderstanding this? And I would say, no, you weren't misunderstanding because it's confusing. Because, yes, it's true that you might not have to do the physical activity to maintain the weight loss if you stay on the drug. But the resistance training is what we're thinking may be important or one of the factors in conjunction with diet and so forth that kind of help preserve the lean muscle mass. And then we're saying there may be even something to the physical activity above just the weight loss. So it's confusing. So you didn't misunderstand it. I think we don't know for sure, and it's a confusing area. What about, let's do another one. I like this one. I'm eating so much less now that I sometimes forget meals completely. This is not uncommon, Jim.

James Hill:
I know, I know.

Holly Wyatt:
What am I going to do about that? Or is that actually healthy long-term?

James Hill:
Yeah, it may not be. Because again, you've got to get adequate nutrition, protein, vitamins, and minerals. What we're seeing are nutrient deficiencies that usually you've seen in a starvation mode, you're now seeing in people that were formerly overweight.

Holly Wyatt:
I'll tell you right now with the clinical trials, the FDA has come out and now are looking at kind of nutrition panels, malnutrition panels, trying to understand what's happening. If people are losing too fast or have lost so much or if their appetite and energy intake has gone to such a low level, we may need to be looking at this differently. So I think this is the important part. We may have to focus on nutrition more, not less, with the GLP-1s.

James Hill:
And that fits in with developing routines so that you don't skip meals, right? That could be helpful. But yeah, I agree. Nutrition is important.

Holly Wyatt:
[45:09] So we had routines so you wouldn't eat too much, you know, routines so you wouldn't overeat. Now we may need routines so you don't undereat.

James Hill:
Cool.

Holly Wyatt:
All right. Do we want to do a vulnerability?

James Hill:
Go for it.

Holly Wyatt:
All right, Jim. Let's do this one. What concerns you most about how people are thinking about maintenance right now?

James Hill:
I think people are still thinking short-term. I don't think they yet understand the difference between weight loss and weight loss maintenance. We're getting there. But again, you and I know when we ask people their long-term plans, they rarely have long-term plans. Most of their goals are short-term. And again, losing weight, which most people would see, that's my goal, is only a tiny part of what your goal should be. And that goal should be keeping weight off and maximizing your health and happiness. So we're still not there. But fortunately, for the first time in a long time, we're moving a little bit in that direction.

Holly Wyatt:
I agree. I think they still want to be done, right? Check the box done and not have to think about it or move into another phase that's going to last their whole lives. But that's what they need to do.

James Hill:
I know. Okay. So, Holly, what part of this whole GLP thing, the conversations, et cetera, what might concern you the most in all this?

Holly Wyatt:
Oh, I think that this is so big and it's moving so fast that what people are doing is outpacing the science. And so when that happens, I think we can make some mistakes. And I think that's good in many ways. I mean, these are really helping people, and I don't want to hold them back. But at the same time, we don't know what we don't know. And the science can't keep up. And we haven't seen that in a while. The science can't keep up. That scares me a little bit.

James Hill:
So I think that's a good way to sum it up. Clinical practice is evolving quicker than the science. And it's going to be a while. We can't just stop and say, “Hey, we're not going to do anything until the science catches up.” So we have to do something. But there's going to be this time, and I think you called it the Wild West, where we're trying things, we're doing our best, but we just don't have the science to back it up.

Holly Wyatt:
I agree. But it's exciting at the same time.

James Hill:
It is exciting. And I will reiterate that Holly and I are not against long-term GLP-1 use. For some people, that works. The exciting time, I think, is that we have so many more tools than we've ever had to manage weight. And in the next few years, we're going to figure out how to use those tools optimally and how different people are going to need different tools, both for weight loss and weight loss maintenance. But I guess if it's one thing I would have people start thinking about, the real goal isn't short-term weight loss. It isn't even short-term weight loss maintenance. It's long-term being able to redefine how you live your life at a lower body weight to maximize your health and happiness.

Holly Wyatt:
Very well said. I like that. Send us your questions, guys. We are getting a lot. People are telling their stories. We still want to have some success stories on here. So if you would like to be on the show and talk about your story, and it's not that you're trying to sell a product, because that's not what we do on this show. But if you want to talk about your story, let us know or send your questions. We are looking at them.

James Hill:
Yeah, and I know a lot of people who listen to our podcast are helping people lose weight. They're dietitians or coaches or whatever. We'd love to hear from you too. What are your questions? What are you learning? What issues do you see out there as you're working with people in real life? But let us hear from you and we'll see you next time on Weight Loss And.

Holly Wyatt:
Bye everybody.

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:
If you want to stay connected and continue exploring the “Ands” of weight loss, be sure to follow our podcast on your favorite platform.

James Hill:
We'd also love to hear from you. Share your thoughts, questions, or topic suggestions by reaching out at weightlossand.com. Your feedback helps us tailor future episodes to your needs.

Holly Wyatt:
And remember, the journey doesn't end here. Keep applying the knowledge and strategies you've learned and embrace the power of the “And” in your own weight loss journey.