The New GLP-1 Questions Nobody Saw Coming

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's episode is a little different. Jim and I have been doing a lot of guest speaking on podcasts over the last few months. We've been doing interviews. We've been speaking at meetings, trying to get the word out about the book, and we've noticed something: the questions about the GLP-1 meds, they're changing. They're not the same questions we used to be asked.

James Hill:
Yeah, it's really amazing, Holly, how the questions are changing. For example, a year ago, what we heard people asking most frequently is, did the drugs work? Are they safe? How much weight I'll lose? Great questions, right?

Holly Wyatt:
Right, right. But now they're shifting. Now we're being asked, why do I feel flat? I was kind of shocked when I got that question, or apathetic, they'll say. Is this changing my personality? I wasn't ready for that one either. Lots of questions about microdosing. Are these drugs currently curing addiction? I've been asked that question. Is everybody secretly on them? And are we moving too fast?

James Hill:
It's really interesting because the science moves slow. It really hasn't changed that much. We have some new information, but I think what we've been impressed with is the conversations are changing pretty quickly.

Holly Wyatt:
And when the questions change, that tells you where the real tension is. So today, instead of diving deep into one topic or a question we've been asked before, we're walking through the new questions we keep getting and what we think they actually mean.

James Hill:
Okay, so what are we going to cover, Holly? What are the questions that we're hearing now that we didn't a year ago?

Holly Wyatt:
So the first big bucket, and I put several of the questions in this bucket, is the question about when people say, I'm feeling flat or I'm feeling apathetic. And the scientific word for that is anhedonia.

James Hill:
Oh, my gosh. Is that going to become part of our dinner conversations? How's your anhedonia today?

Holly Wyatt:
No, I don't know that's how people are going to ask the question. But I think we can introduce the scientific term. Anhedonia means reduced or inability to feel pleasure.

James Hill:
Whoa, that's not a good thing.

Holly Wyatt:
Yeah. So when people are saying, I kind of feel blah. Do these new drugs make me feel blah or apathetic or I don't get excited about anything or my emotions feel kind of flat? That's different types of questions, the way people are wording it.

James Hill:
So what do you think's really going on? I mean, that's a little nebulous, those kinds of terms. But if you drill down, what do you think is going on there, maybe?

Holly Wyatt:
First of all, I want to say that this isn't something they necessarily found in clinical trials. So I think that's important.

James Hill:
Did they look at it?

Holly Wyatt:
But I don't know how they looked at it. And when I start getting this question over and over again, it makes me pause. It's not just one or two. Now I feel the theme or I see the theme that's kind of developing different ways of asking the question, but kind of getting at a blunted response. And they're saying to life, not just to food.

James Hill:
So this is a difference between clinical trials and real life, right? In clinical trials, everything is controlled. Well, you want it to be because you're trying to find out if the drug itself works. But in real life, you see what happens when people use it and they incorporate it into their lives.

Holly Wyatt:
And this is not depression. One thing I want to be very, very clear about, anhedonia can be associated with depression. There is good data to say these drugs showed no signal of producing depression.

James Hill:
So this is different than depression.

Holly Wyatt:
Yes, and there can be some overlap. So I think sometimes when people talk about anhedonia, the inability to feel pleasure, it can be part of being depressed.

James Hill:
You know, Holly, when we were talking to people for the book, we did hear not infrequently this idea that I miss food. I miss the pleasure associated with food. Food is more than just nutrients. It's social activities. It's how we get together with friends and family. So there may be something here that could turn out to be important.

Holly Wyatt:
I think so. So there was no signal of depression, and I want to be really clear about that. The studies looked at that a lot, and there was no signal that these drugs cause depression. But I'm not sure if they looked at this just kind of flattening, how you would look at that. And it makes sense, although we don't have, data, I think it makes sense that you're decreasing the reward pathway. That's one way this works. And yes, that may be for food, but could it be broader than that? Or could people be experiencing that in a way that's even greater than just, I don't enjoy food anymore, I don't enjoy other things in my life? Or they're just flatter. It's not that there's nothing, but there's not as much up and down to them.

James Hill:
Yeah, these brain areas that we think are impacted by these medications, some people talk about them as, this is kind of where we feel pleasure. So maybe it's a lack of pleasure. Is it that when we hit these receptors, which do wonderful things for weight, are we actually reducing our ability to feel pleasure in certain areas?

Holly Wyatt:
Right. These reward pathways, dopamines involve. So is it changing dopamine, which is associated with pleasure? Is it dysregulating that in a broader way in some individuals? Or maybe some individuals are a little bit more sensitive to that feeling for some reason. People say things like, that used to light me up. Things that used to light me up don't light me up anymore, which I think is interesting.

James Hill:
The researcher in me says, oh my gosh, there's so many good research questions we could ask here. If you took somebody and really tried to assess if they're experiencing pleasure before and after taking these medications, I think it would be fascinating to figure out how to do that. What are the things that you get pleasure from right now? Then we give you the medication and we evaluate whether you're getting the same degree of pleasure from those things.

Holly Wyatt:
Right. Is it in some people maybe dampening reward too broadly in the brain, not just around food, but bigger than that?

James Hill:
Well, we've heard that before. Some people say these drugs may work too well. And that may be an example of, you know, the biology is really powerful here. I mean, these drugs work not because they affect willpower, they affect biology, but maybe they're affecting more than just food.

Holly Wyatt:
So how do we put some pie in the plate for people who are listening? Where are we? We don't have data on this necessarily. I want to be super clear. It's not depression. That has been studied, but where do you think? I think we need more science around this.

James Hill:
Well, one is awareness. So one of the things that we've tried to do is to be really as clear as possible on what to expect with these medications. And we've talked a lot about the weight loss There is no question, Holly, we could do a whole show listing all the positive things. The positive aspects of these medications are really amazing. But I think it's also worthwhile having people to understand some of the other things that may not be as positive so that they know what to expect. My guess is that if this occurs, it occurs not in everybody and differently in different people. But it may be some people for which this is a big deal. Other people, yeah, I notice it, but it's really not impacting my life.

Holly Wyatt:
Since I've been getting this question over and over again, I've been kind of asking some people now. That has put it on my radar screen. I'm aware that people are saying this, so I've been asking about that. And people are now thinking about it. It also may be important now that we think about weight loss and weight loss maintenance. This might be something that's not a big deal for six months or a year while you lose the weight. You're like, okay, have a little bit of anhedonia while I'm losing weight. But do I want this for the rest of my life? So if you're experiencing this, does it continue forever? I think is another important thing to think about.

James Hill:
Holly, I love it because you've really distinguished weight loss and weight loss maintenance. And, you know, that's one of our signature ideas is these two things are different. And one of the things that we know is a lot of things people will put up with in weight loss because the weight loss is more powerful than I can accept this and this and this because I'm losing weight. But when you're keeping a constant weight, that differs. And I think people may not be willing long-term to accept the same things they might accept during weight loss.

Holly Wyatt:
Yeah. I think that's important. We wouldn't accept, like, if this was sending you into depression, that this would be a non-starter. But this anhedonia might be okay for a short period of time, but might not be okay for the rest of your life.

James Hill:
Some people talk about a flatness, this sort of like during our day, we're up, we're down, we're happy, we're sad, and this maybe just flattened things a little bit.

Holly Wyatt:
Flattens, especially the up peaks. I don’t know.

James Hill:
And is that good or bad? Is that tolerable? Is it, you know, given all the positive things, is this something we can accept? Or is it something that is going to get old after a while?

Holly Wyatt:
You know, we probably should have a psychologist on that maybe deals specifically with this.

James Hill:
I like it.

Holly Wyatt:
Or maybe researches this, has more. And I've been asked this question enough that I think it's real, but I don't know what it means yet. I don't know how to.

James Hill:
Let's see if we can find somebody who studies anhedonia who might be able to shed some light on this.

Holly Wyatt:
I think that's a good thing. And this moves into our second topic that we're getting more and more questions about. I think they're related, is addiction.

James Hill:
Yeah, very much related. Even early on, people on the medications maybe lost the desire for alcohol or smoking or maybe even gambling. And I think there's research going on to look at the effectiveness of these medications in sort of addressing addiction.

Holly Wyatt:
This is an area that's showing great promise. It is not approved for this area yet, but lots of research going on looking at these new drugs in terms of addiction. And you're right, alcohol, nicotine, gambling, opioids, the gamut, which you can see how that might relate a little bit to the anhedonia that we're talking about.

James Hill:
It totally relates to, if this is your thing, man, gambling, it just gets me off. I get so excited. Now it's just flat. I don't really get the same bolt of whatever from doing this behavior.

Holly Wyatt:
Right. We know these drugs interact with the reward circuits, reward circuits in your brain.

James Hill:
This is biology, what we're talking about. This is not affecting willpower or something else. This is really showing these brain areas that are impacted by these GLP-1-based medications, have very powerful impact on our behaviors.

Holly Wyatt:
And I do think it's going to be somewhat individual. I know I have multiple patients who've told me I'm not as interested in alcohol anymore on these drugs. And I know a lot of people have, providers have talked about that. But it's not everybody. I have people say, no, I still enjoy alcohol or I still want to have a drink. So once again, it may be very individual, but I think this is a promising area to stay tuned on. It seems like there is some interaction in that part of the brain, and we may see new studies and potentially new indications in the future.

James Hill:
Yeah, I think the excitement generated by these medications has really created so much interesting research about aspects of the medication that we might not have even thought of initially. This is good.

Holly Wyatt:
It's good. And that's why I say, I think there's going to be, just like we do before and after COVID, or we talk about before and after 9-11, which was obviously terrible. I think we're going to talk about before and after GLP-1 meds. That's how big an impact, I think, these meds.

James Hill:
Well, it's really been a game changer for our field, right? I mean, we've struggled to come up with any sort of effective treatment until now. And suddenly, we have these amazing medications that not just produce weight loss, they seem to improve metabolic health in so many ways. I mean, it really is. I think you're right. I think we're going to look at life after the GLP-1s.

Holly Wyatt:
I think part of it is it's, I think eventually it's going to extend beyond weight loss, beyond obesity treatment, beyond type 2 diabetes treatment. It's going to be much broader than that. And therefore even impact more people potentially.

James Hill:
So Holly, do you think that pretty soon you're not gonna have to have excess weight in order to use the GLP-1s?

Holly Wyatt:
I do, I really do.

James Hill:
Wow.

Holly Wyatt:
Now, I don't know the dose. I don't, you know, we don't, that's not where we are now. And I do not recommend that now because we need to understand that better.

James Hill:
Very clear, we're not saying go and do it, but…

Holly Wyatt:
You're asking me to, my guess, my best guess or hypothesis in terms of the future, I can see that this has other indications independent of weight.

James Hill:
Well, it's almost if the medications do so much for metabolic health, why would we keep them from people just because they don't need to lose weight?

Holly Wyatt:
True, true. Now, I still, you know, the endocrinologist in me still holds back a little bit and says, there's so much good stuff. I keep waiting. Is there something we don't know that's not good? Because that's usually how endocrine works.

James Hill:
Yeah, it is. And the other thing is, you know, if you combine weight loss with all that, we still struggle to look at what effects are independent of the meds versus what effects are due to so much weight loss. So if If you start using the meds without weight loss, we still need to see are the effects same, the same, et cetera.

James Hill:
But I think that's research that we're going to see happen in the near future.

Holly Wyatt:
I totally agree. All right. Next big bucket new questions that we're getting.

James Hill:
Oh, the pill. Holly, we've got it. We've got the answer. Now we have an oral pill. So everybody's going to take it. End of story. We got to go get new jobs.

Holly Wyatt:
Oh my gosh. When that came out at the first of the year, tons of questions. Everybody wanted to talk about the pill and what did it mean? Did it work as well? Where are we going now? Everybody's just going to be popping a bunch of pills every day or what, you know, what's the future with this?

James Hill:
Which is pretty interesting because if I think about it, and again, I haven't taken the GLP-1 meds and I don't have plans to do it, but taking a pill every day versus a once a week, you just pop a shot. I'm not sure I wouldn't choose the shot.

Holly Wyatt:
It's so funny because for the longest time, people were very anti-shot. I can remember before the new, before the GLP-1s, when we had the other oral meds being on advisory committees for pharmaceutical companies, and they would say, no, people don't want to give themselves a shot. And I always said, it depends on how much weight loss you get. People aren't going to want to give themselves a shot for 3% weight loss. But if you get enough weight loss...

James Hill:
20% weight loss, they'll stand on their head and give themselves a shot.

Holly Wyatt:
They'll get uncomfortable, they'll figure it out, and they'll give themselves a shot. And I think what's happened is they've figured out that these little shots aren't that big a deal. They were a big deal in their head before they knew what they were. “Oh, I wouldn't give myself a shot” because they pictured the shots they get, other types of intramuscular shots and shots that hurt, et cetera. These are tiny, tiny, tiny little needles into your fat, your subcutaneous fat, basically. You don't even feel them going in. And so this amount of weight loss, produce people willing to give it a try, and then everybody's kind of saying, okay, the shot isn't that big a deal. But it used to be a big deal.

James Hill:
It used to be. So, Holly, the big question is, do the pills work as well as the shots?

Holly Wyatt:
So we're going to see. I can say in clinical trials, when you look at the data in clinical trials (and it's not head-to-head, the shot versus the pill), but if you look about all the research that came out when studying people taking the oral semaglutide or oral Wegovy is what's currently available. New pills may be coming, but that's the one that's currently available for obesity treatment. And the weight loss is similar, average around 16%. So, it doesn't look different in terms of efficacy from the clinical trials. However, we know when you get it out in the real world, things can change. The real important part about these oral pills is they have to be protected. So, there's a coating around the pill that protects the GLP-1 so that it doesn't get degraded and gets absorbed. And for the longest time, they didn't know how to do that. And that's why it had to be an injection. They figured this out, but it's still really tenuous, meaning it's got to happen perfectly. So if you take these oral pills, you've got to be very careful how you take them to allow them to get into your GI system and be absorbed effectively.

James Hill:
How do you do that? What are the constraints around how you take them?

Holly Wyatt:
And this, to me, is the kicker. So you've got to take them on an empty stomach. So if you're going to take them first thing in the morning, you've got to get up and for 30 minutes you cannot eat or drink anything. And that's even coffee.

James Hill:
Coffee? Oh, no.

Holly Wyatt:
We take it with four ounces of water.

James Hill:
No, no, no. No coffee for 30 minutes after you get up? This is a non-starter. Give me the shot.

Holly Wyatt:
You get up, you take the pill with four ounces of water. Very specific because you want the absorption to be consistent. You want to get the absorption. And we know that if you don't do this exactly right. You may not get the absorption. You may not get the active ingredient into your bloodstream.

James Hill:
All right, Holly. So help me understand this. I read out in the popular literature, you're a real doctor, so you can address this, is that we have trouble getting people to adhere to taking pills for lots of situations. Now it's not just taking a pill. It's taking a pill under real specific situations. Are you not concerned a little bit about adherence?

Holly Wyatt:
Well, that's why I think the real world, when we have this out, not in a clinical trial where it's very controlled and you have a registered dietitian talking to people about exactly how to take it in the clinical trial, they knew how important it was. We problem solved around how to take this medication. And in the real world, when you may not get all that help or that knowledge or that accountability, I think we are going to see people not doing it correctly.

James Hill:
And the other thing I think about is I think maybe while you're losing weight, you will do this. But we're saying do this forever. And in weight loss maintenance, I just worry that people are going to get a little lax about adherence.

Holly Wyatt:
Right, right. I think that's yet to be determined. So I'm not sure that this, oral version is going to be the version everybody wants. Or if like you're saying, you know, I'd rather get my shot once a week. And future meds, the shot may be once a month, Jim.

James Hill:
Whoa, I see. I definitely do that. And that way I can have my coffee in the morning when I get up.

Holly Wyatt:
You can have your coffee. So I always say if you're a person that you get up and you have to have your coffee.

James Hill:
Me, sign me up.

Holly Wyatt:
The current medication that's available, now maybe newer, and there's other versions of oral pills that may come out that may not require this, require you to four ounces of water, nothing to eat or drink for at least 30 minutes.

James Hill:
Now, my guess is for some people, they'll say no problem. I can get up, I can have the water and pill, and I'm fine. And this is why we've got different strategies for different people.

Holly Wyatt:
And I'll tell you a little trick that people, if they're using the oral pill and that's something, you could, and I know this isn't going to be, everybody's not going to love this, but you could set your, let's say you normally get up at 6 a.m. You could set your alarm for 5 a.m., take the pill, go back to sleep, go back to bed, and then get up and have your coffee at 6.

James Hill:
Maybe.

Holly Wyatt:
Hey, some people, that worked. That worked.

James Hill:
Yeah, right.

Holly Wyatt:
So, we'll see.

James Hill:
Well, this is a good one. We got to watch this one, Holly, because I think we're going to learn some real world data real quickly on the pill.

Holly Wyatt:
Well, now let's talk about some things that are good about the oral. It doesn't require refrigeration, should be easier to get out there. Traveling should be easier and in theory should be cheaper in my opinion, but doesn't seem to be a lot cheaper. So I'm not really sure about that. Should be easier to get out there and take with you.

James Hill:
Okay, Holly, can you use both together? Can you do the shots and when you travel, take the pills?

Holly Wyatt:
Oh, no, Jim, I don't like that. No, because you've got different half-lives. I don't need, let's not even plant that seed. Yeah, let's not even plant that seed because you've got different half-lives, right? And so how is that going to work?

James Hill:
I know, but this is the way people are going to approach this, I guarantee you.

Holly Wyatt:
Y'all, bad idea. Jim Hill had bad idea. Don't go there.

James Hill:
All right, let's move on.

Holly Wyatt:
All right, next segment. Oh, my goodness, Jim. Microdosing. Have you been asked any questions about microdosing?

James Hill:
Everybody wants to microdose.

Holly Wyatt:
Yes.

James Hill:
It sounds so good. You go on the meds, you lose weight, and then you just take a tiny amount.

Holly Wyatt:
I'm not even really taking any. I'm just taking a little bit.

James Hill:
Just a little bit.

Holly Wyatt:
I'm not even really on the med, am I? I don't think I'm even on it.

James Hill:
What do we really know about microdosing?

Holly Wyatt:
And somehow or another, I think I'm not really taking it. So there's that people feel like cheating. So if I'm just taking a little bit, I'm not cheating as much. It's not cheating. We know that's not bad. I think that's a feeling. I also think somehow or another, they think maybe if there's a side effect, it won't be as great. And I don't think we know that. You're still taking the medicine. So I don't know necessarily that a little dose is safer than a bigger dose. but I think people think that.

James Hill:
But where's the science? What do we know? Do we have data on effectiveness of microdosing? Do we know how to do it? Is it a long-term strategy? What do we know?

Holly Wyatt:
We don't. We do not have data on microdosing. We do have data on dosing, though. Every medication does a dose-ranging study of some type where we look at the lowest effective dose and the highest dose. So in a sense, we do have data about dosing. And we know the lowest dose to produce the effect that was needed for the clinical trial for the FDA to approve the medication. And that's how they come up with the dosing. So we do have some of that data, but people are wanting to take it even lower into the micro, meaning less than that lowest dose people start on. We don't have any data, and it really kind of doesn't make sense that it would have a huge impact, although I think people are saying, you know, anecdotally, not with data that's been published, a microdose is working for me.

James Hill:
Are the companies studying this? Are they doing clinical trials around microdosing? Is it in their best interest to do that? I mean, again, pharmaceutical companies, I'm not bad-mouthing them, but they want to position their drug to be effective and to make money. And is microdosing something they would even be interested in?

Holly Wyatt:
Well, so they'd have to do a study and maybe there's, let's say there was 10% of the population that did have impact with a very, very low dose. Do you do a whole study to show that?

James Hill:
Yeah.

Holly Wyatt:
I don't know.

James Hill:
I just wonder if we're going to get any good science around this anytime soon.

Holly Wyatt:
Yeah. The other thing I worry about so much in social media about microdosing and, you know, is it really having an impact? And how does placebo effect come into here, come into this discussion?

James Hill:
Yeah, the problem is, boy, getting your data from social media, that's a little bit scary, isn't it?

Holly Wyatt:
Right, because of the placebo effect.

James Hill:
Yes, yes.

Holly Wyatt:
Right, we know that there is a substantial number of people who, if they believe they're getting a drug and they don't get the drug, but they think they're getting the drug, which would be very similar to a microdose, meaning I'm giving myself something, but not very much. But if they believe that they're getting something and it's going to make a difference, it will. That's why we do blinded placebo trials, because there's always a subset of people that do well on a sugar pill and have really big results.

James Hill:
So what do we tell people about microdosing.

Holly Wyatt:
I'm going to let you do that. What do you want to tell them?

James Hill:
What I would say is we have no data suggesting it's effective. We don't have any data suggesting it's not effective. I think there are some clinicians out there that are playing around with that with their patients. And if you have a doc that really you feel like knows how to do weight management and everything, it's probably okay to work with them on that. But right now, I do not think we can say that microdosing is going to be effective.

Holly Wyatt:
I agree with what you say, and that's what I say on the podcast. The question that I think it leads to is, why are we fascinated with microdosing? Why do we want to microdose? Why not just use the lowest effective dose?

James Hill:
You know, the regular dose works. Why not use that?

Holly Wyatt:
What is in our brain that makes us want to use a really small, small dose? Is it just financial? It could be. It could be financial, but I think it's more than just financial.

James Hill:
I think we're going to need a lot more evidence before we're going to be recommending microdosing.

Holly Wyatt:
I agree. I think this is something to look at.

James Hill:
Something to look at, but it's not a panacea. It's not something that we suggest everybody go out and try to figure out how to do it.

Holly Wyatt:
I agree. All right. Let's move to the next big bucket that we're getting asked. Oh, and I do like this one. Is there such a thing as too little food noise? So finally, Jim, everybody was talking about food noise and getting rid of it and how great it was to not have food noise. And everybody wanted to experience not having food noise. And that was the big thing. And I just want to be on the drug so I don't have food noise. And I get it. I totally understand people who've had food noise their whole life and suddenly they don't feel it. It's like, wow. But I love that it's swinging the other direction. And now people are coming back and saying, huh, is no food noise a good thing? Or is there such thing as too little food noise?

James Hill:
Well, I think the meds have shown that this food noise is not just psychological, it's biological, right? Because when you use the meds, it goes away. So one wonders what the biological purpose of food noise is.

Holly Wyatt:
Exactly.

James Hill:
Is there a reason for it? And it's taking it away... 100% positive? And that's the question.

Holly Wyatt:
Probably if it's physiologic, there's a reason for it. We usually don't have something as strong as that if it's not helpful in some way, at some level, at some point at least. Now, maybe we've outgrown or our environment has changed. Things have changed where it's not as helpful as it used to be. But taking it completely away, is that what people really want. Is food noise the enemy?

James Hill:
Well, and the other thing we talk about, usually when you take something away, something replaces it. So if you take away the food noise, are there other things that are happening to the person in this area? Is there compensation somewhere else? Are they putting energy? Are they putting distraction somewhere else? I would really love for people to start studying that.

Holly Wyatt:
I haven't even thought about it that way. I do think we're seeing some people where the food noise, which is just thinking about food, what am I going to eat? Is it time to eat? What should I eat? If it goes completely away, then there's no drive to really get out there and get even enough calories or enough micronutrients. There's no drive to go to the grocery store and find those foods and put them in your cart or go into your cupboard and get them. So too much, you're thinking about it all the time and the food's there and you're eating it all the time, and none. And you now have to, with your brain cognitively, not your physiology, you have to think about food and really plan for it instead of kind of it naturally being, oh, it's time to eat. What do I have that I could eat?

James Hill:
And again, what we're seeing is we're seeing nutrient deficiencies and people eating too little and so forth. And I wonder if some of that might be related to reduction in food noise.

Holly Wyatt:
I think it's funny. We tell people food logging is helpful when you have a lot of food noise. So you kind of plan out your day, you log your food, you kind of use some cognitive skills really to decide how much you should eat when food noise is telling you to eat all the time. And you have to log your food and everybody, I'm tired of logging my food. Now, when people have no food noise, I'm like, we have to log our food.

James Hill:
Yeah.

Holly Wyatt:
We have to log our food for a different reason, to make sure you get enough protein, to make sure you get enough micronutrients. So, the extremes require logging. Really, in the middle might be the best place where you're naturally determining it.

James Hill:
A little bit of food noise, but not too much.

Holly Wyatt:
Too much. Just right.

James Hill:
Anything to get away from the food logging, Holly.

Holly Wyatt:
Right. That's what people tell me. They don't like to food log for long periods of time.

James Hill:
I agree. All right. Well, let's move to the next one.

Holly Wyatt:
Yes.

James Hill:
[33:54] Holly, is the Ozempic face real?

Holly Wyatt:
All right. So, it used to be face, and we still get face.

James Hill:
Oh, it's broadened?

Holly Wyatt:
Oh, oh, now, you've got to tell me you haven't been asked about Ozempic teeth?

James Hill:
No.

Holly Wyatt:
Oh, teeth. Yes. Toes, fingers, Zempic everything. And Jim, this was only once. And I got to say, I'm glad it wasn't. I won't think I was on camera because I'm sure my face was like, what? I'm not good. I'm not good at poker player. Even Ozempic vagina. If you had been on there, I would have given that question to you. That would have been yours.

James Hill:
I can handle that one I was like.

Holly Wyatt:
I was like, no, I haven't heard that. But I will do the best to try to answer this. So many questions about, you know, is Ozempic, and it's funny that Ozempic was chosen. I think it's any GLP-1, new generation GLP-1.

James Hill:
Is this a weight loss effect or is it a medication effect?

Holly Wyatt:
So everything would point to it being a weight loss effect. We have no data that there's something specific about Ozempic or any of the new generation GLP-1s doing something specifically to your face that's making it look older, which is what most people are saying. the wrinkles or sagging, that deflated kind of looser appearance is coming from fat loss. And we've talked about this over and over again. You don't get to pick where your body burns fat or where you lose the fat.

James Hill:
So I get it with the face and toes and fingers, even vagina, but teeth?

Holly Wyatt:
Teeth.

James Hill:
How would weight loss affect teeth?

Holly Wyatt:
So this is a little bit different, right? This falls into a different category. It's decreased saliva production and different, you know, changing in how you're eating in the saliva, which is producing changes in the oral cavity. So that's a little bit different mechanism, I guess. But once again, still not directly like the medication is going to your teeth and doing something to it. It's still kind of, I guess, a side effect in that sense versus losing the fat.

James Hill:
So, Holly, do people see this as negative? I mean, if you've got too much fat to start with and you lose fat, what's the downside to all this?

Holly Wyatt:
People care about how they look.

James Hill:
And it makes you look bad when you lose fat from your face? You look worse?

Holly Wyatt:
Well, because it's sagging, Jim, and wrinkles and stuff. That's not usually what people want.

James Hill:
I'm trying to understand this.

Holly Wyatt:
It's deflated. It's looser. It's, you know, I don't really get the fingers as much. You might have to resize your rings or something. But I get the face. I wouldn't want all the fat to come out of my face. That probably wouldn't make me look healthy or young or vibrant. You see this now, the dermatology clinics are coming out and saying, come to us and we'll prevent this from happening. I don't know how they're going to prevent it from happening, but they're talking about preventing or they're talking about using fillers or fat, putting fat back in your face. So it's a big business out there.

James Hill:
You solve one problem and you create three more.

Holly Wyatt:
Yeah, yeah. So lots of questions. I think the bottom line is, you know, weight loss changes our bodies by losing the fat. The drug isn't going in there and doing something specific.

James Hill:
But it's not surprising, Holly, that for many people, years and years and years of being overweight and stretching the skin and everything, that when you lose weight, it may not be surprising that the effects aren't all positive in terms of how you look.

Holly Wyatt:
I think if you compare this to bariatric surgery, I don't think it's any worse. People who lose large amounts of weight with bariatric surgery quickly have skin surgery, basically. So I don't see this as any different.

James Hill:
So weight loss changes your body.

Holly Wyatt:
Exactly.

James Hill:
It's not the drug changing things. It seems to be the weight loss changing things.

Holly Wyatt:
That's what everything would look like thus far.

James Hill:
All right, Holly, but the next one, help me out here. Hair loss?

Holly Wyatt:
Okay, I put this because if I haven't...

James Hill:
Does GLP-1 meds cause hair loss?

Holly Wyatt:
So I don't know what I did, Jim. I guess I looked something up or somehow in my social media, I don't know, it's almost like they can hear me or something. All of a sudden, I started getting all these Instagram posts, et cetera, about hair loss. And then I was getting all these questions about hair loss. And so this to me is a big thing right now. Everybody's talking about hair loss on these GLP-1s and what do you do about it? And so I had the standard answer. Hair loss is not new to weight loss. I've been asked about hair loss my whole career. And it's not uncommon when you lose weight, especially lose weight rapidly or lose a lot of weight for your hair to shed. And there's lots of reasons for that. Decreased calories, lower protein, deficiencies in micronutrients, hormonal shifts. And then just when you're kind of going through stress in general, all the hair follicles can sometimes line up into, they all go into a resting phase at once. And you can lose or shed a lot of hair, usually two to three months after that happens. We see that a lot. But wow, now everybody is really talking about it.

James Hill:
Holly, we got to get a dermatologist on to talk about all this because they're the ones that are probably in the trenches seeing people come in with complaints.

Holly Wyatt:
Yes, I agree. There's so much out there right now in the social media world and I'm getting so many questions. It feels like I need someone who has expertise in this area. Can they really say, is the scalp changing? People are saying the scalp's changing. That makes no sense to me, but is the scalp changing? So let's bring someone in who has some expertise.

James Hill:
We've got a great dermatology department here at UAB. Let's reach out and get somebody and get them on to talk about this.

Holly Wyatt:
Yeah. I would say I haven't seen any data published that shows there's something unique about the GLP-1s doing something to the scalp or doing something to the follicles that's independent of weight loss. I think we can ask, what are the hair specialists, the dermatologists, seeing?

James Hill:
People want to know. Let's get them on and ask the questions of people that know the answers.

Holly Wyatt:
Yeah. So we need a psychologist and we need a dermatologist that specializes in hair.

James Hill:
If anybody's listening and fits those bills, let us know and we'll put you on.

Holly Wyatt:
We want to hear. All right, next part, this idea of non-responders versus super responders. People are starting to use those terms.

James Hill:
Well, we know that people differ. I mean, you and I have a friend that doesn't do well on the meds. We know other people that have done super well. We had somebody on our podcast a couple weeks ago that just lost 120 pounds, loved it, no problem super responder. Our friend who's been on it hadn't done very well. What's going on here?

Holly Wyatt:
That's normal.

James Hill:
What?

Holly Wyatt:
It's normal. We always have non-responders for any drug and super responders. I mean, that's normal, but people are really talking about it. I didn't lose the 28% that this some people on this drug lost, or I didn't lose as much as my friend. And seeing this individualization. That is almost always true with any medication.

James Hill:
Do we know why some people don't respond well?

Holly Wyatt:
I don't think we know that very much. Jim. Do you know of any studies that are characterized?

James Hill:
I don't think so. The meds are having the same impact. They're going to GLP-1 receptors, right? And the question is, why in some people do you have a huge effect and in other people not so much? I think that would be really interesting to try to understand that a little more.

Holly Wyatt:
[42:22] Really look at the non-responders. Maybe look and study the non-responders versus the super responders.

James Hill:
Absolutely.

Holly Wyatt:
You might see where they're really different.

James Hill:
Do we know that if you're a non-responder to one type of med, say semaglutide, you might respond to tirzepatide?

Holly Wyatt:
We do know that. And yes, if you don't respond to one, that does not mean you won't respond to the other one.

James Hill:
Ah, ah.

Holly Wyatt:
So if you didn't respond to semaglutide, you can try tirzepatide and you may respond.

James Hill:
So that's actually positive, right? And as you and I know, there are going to be more meds coming. So the idea is hopefully there's going to be one that works for you. Not everyone may work for you. And that's where the clinician is going to have to use some clinical judgment there in helping people find the right medication for them.

Holly Wyatt:
Just like blood pressure meds. Sometimes you put someone on a blood pressure med and doesn't do very much. You even push the dose up and it still doesn't get you the effect you want on lowering the blood pressure. So you switch or you combine. That's how medicine works.

James Hill:
And there we have so many options. And I think the problem so far with weight is we've had fewer options. Now we have two, but I think that's going to increase very, very rapidly.

Holly Wyatt:
And one of them is just the GLP-1, and then transepatide is GLP-1 and GIP. But even if you had another drug that came out, let's say, that was just another GLP-1, they're slightly different. The drugs aren't identical. That could be important, too. So even trying that when it's the same receptor, but a slightly different drug. All right, Jim, next question for you. I get this a lot. Do we need more? Do we need different drugs? The next drug coming out or very soon may be a drug that gets us 28% weight loss on average.

James Hill:
So, Holly, what I would say is we're going to get better and better at producing more and more weight loss, But we still have the second half of the game keeping the weight off.

James Hill:
[44:40] And that's where I think our biggest challenges are going to be. And I think we're actually going to see medications positioned for maintenance, where you have a medication for weight loss and maybe a different medication for weight loss maintenance.

Holly Wyatt:
[44:58] I agree. I think we need bigger guns. People are like, well, we have enough weight. I'm like, no, I think we can have bigger guns, but we just need to know when to use them and which people. What are the side effects? If you're losing 28% weight, that may really watching what's happening to muscle, really looking at any kind of deficiency you may have or other side effects that might come from that or effects of that much weight loss. But I think the more tools we have, the better we're going to be able to individualize, personalize it, and have more people have the effect they want and minimize side effects. And then I do think what we're seeing is, what do we do in weight loss maintenance? And is there different drugs for weight loss maintenance? Do you come off the drugs in weight loss maintenance? Do you do a little bit of behavior and drug? That's wide open, I think.

James Hill:
Yeah, and I continue to believe it's the combination of medication and lifestyle that is really going to be the sweet spot going forward. I just don't think medications alone are going to give people the success, not just in weight loss, but in quality of life. But I do think there's a lot of potential for combining medications and lifestyle.

Holly Wyatt:
Yeah. All right. I'm going to combine two of our last buckets because I think they're opposites and they happen together. I'm getting questions about why do people still whisper? They'll do this to me. I'm on the drug don't tell anybody I'm on the drug I'm like who's here which leads to the second question is everybody on the drug yeah, So, why do you think this is the case?

James Hill:
Well, I don't think everybody's on the drugs.

Holly Wyatt:
Okay.

James Hill:
But I do think people, for some reason, feel a little bit embarrassed about being on the drugs. And I think it's this idea that you're cheating. You should have to do it with pain and suffering and lifestyle change. And this is just too easy to take the meds. And we've said over and over and over, that's a terrible way to think. The meds are leveling the playing field. You were behind the eight ball to start with. The medications put you even with people that haven't had these issues.

Holly Wyatt:
Yes. I think the whisper is because people still feel like it's cheating. There's that stigma. So they whisper it. I definitely think that's what's going on.

James Hill:
We've got to stop that. These are tools. These are legitimate tools. do not let that be the reason you don't consider the medications.

Holly Wyatt:
Absolutely. All right, Jim, let's go to vulnerability questions. I think we've answered a lot of questions our listeners have been asking, but let's move to some vulnerability questions.

James Hill:
Okay, Holly, I'll start with one for you. What of these new JLP1 questions surprised you the most? You can't use the one about the vagina. You have to use another one.

Holly Wyatt:
Really, Jim? You're limiting me there. Yeah, you know, I think... What surprised me the most probably is about the anhedonia. I hadn't really thought of it that way. I knew the depression data, that these weren't causing depression, but I hadn't really thought about that kind of apathetic. And I think it's really interesting, and I hope that we look at that a little bit more. So that was probably the most surprising or interesting for me to think about, at least. So, Jim, here's a question. What concerns you most about where the public conversation is heading?

James Hill:
Yeah, I actually think a lot about this one, Holly. And at some level, is the way to solve obesity the medical solution or is it the social solution? And what I mean by this is what we know with these medications is once you have someone that's obese, we can use the medications and get the weight off. But the real issue is what's the problem that created the obesity problem in the first place and is addressing it as a medical issue, taking away from efforts to address it as a social issue. I think most everybody would agree that obesity arose with a mismatch between our environment and our biology. The environment we used to have early in human development wasn't obesity-producing. The current environment is. are we going to give up efforts to address the environment and just say, well, we have wonderful tools, and when someone becomes obese, we have tools now to help them get the weight off. So I hope in pursuing the medical model, which is fine, I think absolutely it's wonderful to help people that need it, but I don't think it takes away from our need to really address what led to the obesity epidemic in this country in the first place. And that's largely addressing our environment.

Holly Wyatt:
Right. Which leads to a follow-up on that for me. Do you think that we're moving too fast compared to the science?

James Hill:
[50:33] I actually don't. I actually think that the problem has been that for decades, we've watched obesity rates go up and up and up, and everybody says, oh my God, we have to do something or we're all going to become obese. We have tools now. We're using them. I say over and over, we don't totally know the best way to use them yet, but I don't think you can keep these tools on the shelf. I think you have to get them out there. So I think it's up to the science to keep up. And I think we have wonderful opportunities to do that. And to me, studying some of these things is a huge urgent priority. So let's continue to use the tools, but let's do everything we can to help the science catch.

Holly Wyatt:
I like that. Science needs to catch up. Like that. All right, let's put some pie on the plate. This was a good one. We covered a lot.

James Hill:
These medications are powerful tools. People know that. They've experienced the positive parts, the weight loss, etc. Now they're beginning to ask some different questions. And these questions relate to what happens in real life when you use these medications. And I think we're going to get some answers. Unfortunately, we don't have a lot of answers yet, but I think we will get them. And I think it's important that people are aware of things that are going to happen, like anhedonia and the Ozempic space and so forth. So they at least expect some of these things and they're not a surprise.

Holly Wyatt:
And this is where I think what you said at the end makes sense. The science needs to keep up. We need to be listening to these questions that are coming up over and over again and then studying them, right? Putting them back there.

Holly Wyatt:
That's how I think it would work best. So I love that answer.

James Hill:
All righty. Well, this has been a really interesting session. I've learned a lot, Holly. And we appreciate everybody listening. Send us your questions, send us your comments, and we'll see you next time on Weight Loss And.

Holly Wyatt:
Bye, everybody.

James Hill:
Bye. 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.