All About GLP-1 Weight-Loss Drugs

Dr. Robert Rountree:

This is the Thorne Podcast, the show that navigates the complex world of wellness and explores the latest science behind diet, supplements, and lifestyle approaches to good health. I'm Dr. Robert Rountree, Chief Medical Advisor at Thorne and functional medicine doctor. As a reminder, the recommendations made in this podcast are the recommendations of the individuals who express them and not the recommendations of Thorne. Statements in this podcast have not been evaluated by the Food and Drug Administration. Any products mentioned are not intended to diagnose, treat, cure, or prevent any disease. 

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Hi everyone, and welcome back to the Thorne Podcast. We're really glad you're here and are excited to talk about some fascinating topics for you today. For this episode, I'm joined once again by friend of the pod and Thorne Vice President of Medical Affairs, Dr. Amanda Frick. How are you today, Amanda? Anything interesting going on in your life that we should know about?

Dr. Amanda Frick:

Well, there's always something interesting, isn't there? It's just whether anyone wants to hear about it; that's the problem. I am really excited about a new gym that I joined, so a new place opened right near Thorne, and as soon as I saw it, I got super excited. Since I moved here, I haven't found a home, a home base for a gym, so I've been waiting for one that sort of fit what I had been used to on the West Coast, and there are not just that many options here, and I just love being excited about the gym again. It's just so happy to… what they offer. And they also have hot yoga and they have really beautiful... it sounds so silly, but they just have really beautiful locker rooms and it's like you feel good wanting to go there, which makes it easier to go right?

Dr. Robert Rountree:

So do you do more solitary stuff like weightlifting? Or do you do more classes?

Dr. Amanda Frick:

I do both, but the membership that I have is more class-based, and then I have the open gym. I used to be a free-weight lifter, so I do want to utilize those, but the classes, like, I know what my mental weaknesses are and needing to be somewhere at 5:30 makes me actually go. So signing up for classes makes me go.

Dr. Robert Rountree:

Well, I have to say I love my gym, which is really just a community rec center, but they have a great pool and I get in there a couple times a week and swim a mile and a quarter twice a week, and I love it. It really keeps me going and helps me build strength and muscle mass and all kinds of stuff. I think swimming is kind of underrated by people that don't do it, but if you look at these Olympic swimmers, they are built.

Dr. Amanda Frick:

They are fit. Yes.

Dr. Robert Rountree:

Yes, yes. So it's like, OK, I can emulate that. I'm going to head towards that. 

So the topic we're talking about this week is really one that is hot. It's taken the world by storm, to use the cliche. There are lots of conversations going around about the topic. I'm sure you've seen it in advertisements, heard about it on the news. There are many different brand names, but at the core what we're talking about is the GLP-1, glucagon-like peptide-1 weight loss drugs, and the related class, the GIP-related weight loss drugs and medications. So this is a huge topic, isn't it Dr. Frick? How about you start us off with the basics of what these drugs do and why they're so popular?

Dr. Amanda Frick:

Sure. I will try to keep it simple, but basically they have an effect on multiple areas in the body that are making it easier for people to regulate their own food intake. So in the brain, it's helping to make you feel full, helps you not feel as hungry or have as many cravings, but also at the same time helps you to feel full faster or you feel like you've eaten enough in the same way in the stomach, it's kind of slowing down the way the food moves through your body. It slows gastric emptying. So the food stays in your stomach, literally in your stomach a bit longer, so you're feeling full for longer. And then in the same way, it reduces some gastric acid secretion. So the food has to be digested slower in your body and then in the liver, it's helping control your blood sugar by enhancing blood-sugar control and enhancing fat metabolism and then directly in the pancreas by supporting increased levels of insulin.

So insulin resistance, I think we've spoken about before is really common, but your body's not listening to your insulin anymore. And so this is helping with increased insulin, so your body has a response which decreases glucagon and then helps to balance your blood sugar. So they really started as blood-sugar control drugs, but people were seeing such massive weight loss on them. I mean, they really started as marketed diabetes drugs, and that's the only way you should have been getting them. But now the brands, the major brands have created weight-loss versions that are approved by the FDA for the use of weight loss because they're so effective at it.

Dr. Robert Rountree:

So that's an important point, which is these are not really new drugs, or at least the category. It's not that new. I mean, I don't remember the generic form, but I think the first one was Victoza or something that's been around for at least a decade or longer. So it isn't like this just popped out of the sky one day. It's more that they were giving these drugs to diabetics and people were saying, "Hey, I'm losing weight." And of course the company's making it went, "You're losing weight? That's a good thing." 

Dr. Amanda Frick:

Bonus!

Dr. Robert Rountree:

Yeah, that's an added bonus here. I have to say, many decades of practice, I've seen a lot of drugs come and go, but there's something different about this class of drugs.

Dr. Amanda Frick:

I agree. I think there's always a lot of hate around something that works well for people, and people are really sensitive emotionally to weight loss, and we have a tendency to discredit others for their weight loss, and I think that that's a self-protective mechanism. So this sort of concept of “These are cheating,” or these are... "You're not doing it the right way or you're not working at it," is just really unfair.

Dr. Robert Rountree:

Well, when they first came out, I was so skeptical. I was highly skeptical, and I thought, "Well, the last thing I'll ever do is prescribe these things," and then I add patients come in and say, "I don't really care what your opinion is. I want them." I've had several people say that, and they're like, "Will you prescribe it and just help monitor?" And I have to say for the right person, they can be quite effective, to my amazement. So it's really easy to dismiss them, I think from the perspective you were talking about, but there's something going on here.

Dr. Amanda Frick:

They really, really work. One of the things I love about them is they're working in so many different ways that make sense. It's not like Phentermine. It's not a drug that's like speeding you up and dangerously amplifying your metabolism and increasing your heart rate, and then you're worrying about it. To me, what I love about it is that even though they're not designed to have you make better choices, the way that they're controlling the hunger and the cravings and helping you feel full longer, you can make better choices. It's amplifying such a good opportunity without, I don't feel like they're overtaking your body. It's helping them realize a signal that they either have grown to not listen to, or I do believe there's a genetic component to how these hunger regulating hormones work.

And when people are low in estrogen, in perimenopause, we give them estrogen. We support them with something that they need. And I think that the more we learn about this, we'll understand that some people have decreases in these hormones and their activity in their body, and so we're just assisting them with that. And I just really love the concept.

Dr. Robert Rountree:

So I think maybe one of the most profound understandings that's come out of this is a new appreciation of how genetics and metabolism play a role in people's weight because the moralists in the crowd have said for years, "Well, you're an overweight person because you eat too much and you don't exercise enough. And that's the whole story," and these drugs have really changed the perspective on that. They said, "Well, wait a minute, maybe there is something that's different about the metabolism of somebody who's really overweight."

I've got to say, I've seen patients that were on a perfect diet, that go to the gym five days a week, they work out vigorously, lift weights, go to classes, and they still have more body fat than is optimal. They're still heavy, and they're scratching their head and going, "What am I doing wrong?" So the old notion that if they just ate the right diet and they just exercise enough, they would be fine. But suddenly they go on these drugs and the weight just melts away. I mean, they're not magic, but they're definitely doing something that is helping us understand the physiology of metabolism. Would you agree?

Dr. Amanda Frick:

Yeah, I would. I would agree.

Dr. Robert Rountree:

So what do you think is the future for these drugs? Do you think this criticism that once people go on they have to stay on them forever? Do you think that's true, or do you think we're going to be able to find the new set point for people so that they don't have to keep taking them?

Dr. Amanda Frick:

I don't know if we've had them long enough to know that. I think so far, I do believe people need to be on them for a long time. I'm not sure we've had people on what I would call a maintenance dose for long enough to know if when you revoke them, if it's going to immediately come back. Theoretically, if you get used to eating smaller amounts, you could adapt to that, but that's not magic. You don't take a drug for a week, you eat less, and then it stays that way. So I think we still need to learn. It's such a great opportunity for the people using the drugs to modify their habits and figure out what makes them feel good and works for them. But I do think it's possible that particularly in individuals that we think that their weight management is related to these underlying imbalances. Yes, it's possible that they could need to stay on a maintenance or smaller dose to maintain weight.

Dr. Robert Rountree:

Yeah. For a long period of time.

Dr. Amanda Frick:

For a long time.

Dr. Robert Rountree:

And at this point, we just don't know what it means to be on one of these drugs for say, five years.

Dr. Amanda Frick:

Right.

Dr. Robert Rountree:

Well, except we've had diabetics on the Victoza or drugs like that. We've had diabetics on those for a long time and haven't seen a problem.

Dr. Amanda Frick:

But it's also possible the longer that we have people on them, the longer we're going to learn or the more we're going to learn about the other potential upsides. So there's so many other things saying reduction of cardiovascular disease risk. There's complete reversal of prediabetes with these drugs there. I mean, reduction of long-term chronic health complaints by utilizing a drug could always happen, and it could be just related to the weight loss itself, but those are massive risk factors that you could reduce.

One of the things that's less talked about, which I find really interesting I try to read about a lot, is the mental-emotional effect that they have for people. So it's like quiets a food noise. So people who have binge-eating or they just have poor eating behaviors or they're not controlling it well, it takes away the chitchat in your mind about constantly thinking about food and then feeling liberated by that. And then even people just reporting, even if they weren't binge eater, didn't feel like they had portion control problems, that they're feeling like they have a better mood with these drugs. So I just love the aspects of that. It makes me so happy for something that I've read forums and people online, and it's like they're saying it changed their lives, and I believe that it has.

Dr. Robert Rountree:

Are there any signals emerging? And that's kind of a scientific term when we say, “Is there a signal?” which means are we seeing evidence that there are any problems that emerge with these drugs that we can correct with say a certain kind of exercise or nutritional support or anything like that? Let me just put it differently. Is there anything we should be doing to support people while they're on these drugs? Is it just a matter, "Hey, you're overweight, here's your shot, see you later"?

Dr. Amanda Frick:

I think it depends on the user and the doctor. So maybe that's all the user wants. That's possible. Meeting your patient where they are and what's going to work for their lifestyle. That's one thing. But yes, definitely there are studies showing 150 minutes of exercise a week help the drugs to work better. There are the side effects that we discuss or the social media storm aspects of the “Ozempic face” or sagging skin and the aesthetic aspects. So taking care of yourself, making sure you're eating plenty of protein, having weight training exercises in there to maintain muscle mass so you don't have as much sagging skin. There are definitely ways that you can adjunct your GLP therapy.

Dr. Robert Rountree:

So good nutrition doesn't go out the window. You still need a whole-foods diet and getting all your beneficial phytochemicals, your berries, your salads or things like that are all still really critical, right?

Dr. Amanda Frick:

And maybe even more critical because the amount of food, when this is really working, and for people who have a lot of weight to lose, the doses that they end up taking, their food intake becomes massively smaller than prior. So if you're not prioritizing protein and nutrient density and colorful foods, you could actually be taking in less nutrients if you don't pay attention. So arguably, it's even more important to look at the nutrient density in your diet if you're eating so much less.

Dr. Robert Rountree:

It's not just a matter of getting the prescription and off you go. Maybe you should see a nutritionist.

Dr. Amanda Frick:

I think that most people could probably benefit from seeing a nutritionist, but there are really simple things that you can do too, like we were talking about with nutrient density and some specific nutrient gaps.

Dr. Robert Rountree:

All right, well, I think we're going to get into this a little more detail with the questions, but now we've got to take a short break and when we get back, we'll spend a little extra time on questions that have come in from our audience.

Dr. Amanda Frick:

Sounds great.

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And we're back. So now it's time to answer some questions from the community. Our first question this week comes from a listener who asks, "What are the most common side effects of GLP-1 agonist? And Are there ways to mitigate these while still achieving weight loss?" And I'm going to throw in my part of this, which is that I've seen news headlines that said, "Oh, the biggest problem with these drugs is they make you lose muscle mass." So is that true? And what about other side effects?

Dr. Amanda Frick:

I think that while it may be true, it's blown out of proportion. So any kind of weight loss method that has someone lose 20% of their body weight in a rather rapid amount of time, you could potentially have loss of muscle mass. So it's not like these drugs are out there attacking muscle worse than any other diet you could possibly have. They just work so well that that's part and parcel of the package, I would say. But it doesn't mean there aren't things you can do to help protect your muscle mass with diet and exercise and lifestyle modifications.

Dr. Robert Rountree:

The other side effect I've seen is nausea. And I remember when Ozempic first started being heavily promoted, they really made it sound like that nausea was just a terrible thing. And I have to say, I haven't had people really complain about that. They just said, "Yeah, in the first week or two, I felt a bit nauseated, but I don't experience that anymore." So I was expecting this to be terrible. I mean, I've seen reports, “Oh, people are vomiting, they can't hold food down.” Well, I think if you start with the lower doses, then you don't really see that. Is that your understanding as well?

Dr. Amanda Frick:

Yeah, mine's really similar. So I think tendency for nausea and other GI upset happens when you first start and then every time you change a dose. So for people who are not familiar with it, you start at a very low dose and then you go up in really small increments until you find something that's effective and you start to lose weight, which not everyone does right away. It takes some adjustment of dose, but whenever you're increasing to something that's a little stronger, those side effects may kick back up if you jumped dose. So I was reading a lot, especially when Mounjaro had a $25 coupon out there, and then so many people were utilizing it that people couldn't get the doses that they need, but they were so happy with the result that they were just skipping doses and just taking whatever there was.

Dr. Robert Rountree:

Oh, don't want to do that.

Dr. Amanda Frick:

Yeah. So I think changing a dose of any drug too quickly could have negative side effects and that could contribute, but not even just nausea. Because food is delayed from emptying in your stomach, you can get feeling a little bloated or gassy. Some people get like burpy and have a lot of belching because the food is lingering in their stomach and those things get worse when you haven't adjusted yet. So your brain and your stomach are saying like, "Oh, we're OK.” But if you're used to eating that same size portion that you would always eat, or “I usually eat four pieces of pizza," and then you're putting it in there, overeating can make that worse, too.

So adjusting to smaller or more frequent times when you're eating food, don't eat too close to bedtime because then you're laying down and the food's sitting in your stomach and sort of moving up the wrong direction. And then overly fatty or greasy foods for the same reason because they're sitting in your stomach for so long, they could be really hard to process the excess fat, particularly because it's decreasing your gastric acid. And so you need that to break the fat up. So that could be helpful. And then of course, avoiding alcohol. It's empty calories, and anyone that's looking to lose weight should consider reducing or eliminating alcohol, but also it can sort of confuse the system. And you're taking a drug that's modifying insulin and affecting your blood sugar and drinking alcohol while doing that could make you more prone to having hypoglycemia.

Dr. Robert Rountree:

So you're going to have to make some changes in your diet if you're on this drug. And that's just the way it is.

Dr. Amanda Frick:

Yeah, it is. It's part of your commitment to the process.

Dr. Robert Rountree:

So next question, and I'm actually going to roll some of these together. Is the drug really that good? Isn't there a more natural way to achieve similar results? Several people ask, "Well, is there a supplement I can use that will do this? Or how do I make GLP-1 go up on its own?" So it seems like there's a couple of different parts to that. “Can I lose weight without taking these drugs?” That seems like the first part. And then, “Can I activate this specific pathway without taking the drug?”

Dr. Amanda Frick:

So the first part, can I lose weight without taking these drugs, is yes because we know of lots of other ways that you can lose weight. Does this drug make it infinitely easier? Also yes. Even if you're doing all the same things, just adding this drug is going to make a massive change and in a way more expedient time. And I do think we've identified natural compounds that can mimic slightly what the drug activities are, for these GLP-1 and GIP drugs, but they're not going to come anywhere near what the drugs are doing. 

Dr. Robert Rountree:

They're not as strong.

Dr. Amanda Frick:

No. Anyone marketing a supplement to work in the same way as these drugs, you should think more than twice about the validity of that claim.

Dr. Robert Rountree:

So there's some probiotics, there's some natural chemicals, things like that that are being sold as GLP-1 agonist, etc. So maybe they do raise GLP-1 in the body, but if a person's really got a problem, it's probably not going to be enough to replace the drug. Maybe it will help support the person that's on the drug?

Dr. Amanda Frick:

Yeah.

Dr. Robert Rountree:

A possibility.

Dr. Amanda Frick:

It's a possibility. It's also a possibility that that's a bad idea. So if you're taking a supplement to sort of balance your blood sugar and you're taking a blood-sugar modifying drug, you may not want to be stacking those, and then you double whammy and then you have low blood sugar and you feel poorly or hurt yourself. But there are supplements you can take to balance blood sugar, but they're not going to be working in the same way that this drug, it's just so much more potent. Now, from the side effects standpoint, there are definitely things you can do to help your digestion, to help with some of those side effects. I would think of them more like side effect management than I would think of them making the drug work better.

Dr. Robert Rountree:

So this person says, "I've read GLP-1 can result in a positive mood. Why? Is it affecting the brain?"

Dr. Amanda Frick:

Well, we know it affects the brain, but we can't say exactly why it affects the brain to increase mood. We were talking about that a little bit before. That's why I find it so fascinating. Do you have any sort of theories about why it would affect mood?

Dr. Robert Rountree:

No.

Dr. Amanda Frick:

OK.

Dr. Robert Rountree:

No, no, other than... I mean, the main thing I would say is that we initially thought, hey, these are just appetite suppressants and motility drug. It turns out that there are receptors in the brain, all over the brain, for GLP-1. So clearly it's got other effects on neurotransmitter production than we never imagined before. So there's something else going on that I don't think we've uncovered yet.

Dr. Amanda Frick:

I mean, this is complete speculation from my standpoint, but when you have intrusive food thoughts or you're constantly thinking about food or it becomes like the way you seek happiness when... There's flip sides to this, but if you don't have that noise all the time or something chattering at you all the time, it's almost like there's free space in your head. And I think that that's part of it. I think they release from that. People are saying it's like curing their food addictions and their binge-eating. There's just so many psychological positive aspects. Now, on the flip side, if you are a person who maybe doesn't have a lot of other sources of joy in your life and your food is your joy in your life, then there are reports of people feeling like a lack of joy or they're missing out on something because they don't have desire to eat. And that was primarily where they were getting their dopamine. So it can go either way. I think a healthy mindset about it and keeping balance in what you're eating and doing are still really important.

Dr. Robert Rountree:

So I think our next and last question is going to be one that kind of ties in with this whole thing about food in general, which is there's a long list of foods to avoid on these drugs. So I assume the person is saying that's what they've seen in the drug literature that comes with it. "Some things like sweets, baked goods, I can understand, but why no juices, dried fruits, fresh grapes, bananas, pineapples, watermelon? I thought those were healthy food." So I can't say I've seen that list before, but maybe you can talk about diet issue in general with these drugs.

Dr. Amanda Frick:

I have not seen that list before either. But at first glance, if I was trying to separate it out, those are some of the highest glycemic index fruits. So that's my guess. It's not that they're making the drug work less or that they're hurting you rather than… Controlling your blood-sugar balance is part of why the drug's working, and especially if you're a diabetic, you should be avoiding these things anyway. So I think there's probably some mismatch there with just high-sugar fruits and avoiding those.

Dr. Robert Rountree:

I guess the last thing I'd ask is where can people go if they want more nutritional information about things they can do that will help with weight loss? What are good resources for that?

Dr. Amanda Frick:

Yeah, we have a couple actually different options on Thorne.com. So we have a weight loss guide that's more focused on not GLP-1 drugs, but exercise changes, some nutritional support, diet, lifestyle recommendations. And then we also have a medically guided weight loss guide that we made for our customers. So for those of you who are taking GLP, GIP drugs or interested in them, we created a program to help guide people to understand what kind of food choices might be best, what are commonly prescribed drugs, how do they work, and how to manage some of those side effects with food, exercise, and a couple of supplements. So if you're interested in reading more, you can go to Thorne.com and at the bottom, click on Wellness Guides.

Dr. Robert Rountree:

Wow, that sounds like a great resource. It's all free?

Dr. Amanda Frick:

All free.

Dr. Robert Rountree:

All free. Excellent. All right, folks, that's all the time we have this week, so be sure to leave a comment and subscribe to the show. We really, really appreciate it. Thanks for listening and thanks again, Amanda, for podcasting with me. 

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Thanks for listening to the Thorne Podcast. Make sure to never miss an episode by subscribing to the show on your podcast app of choice. If you've got a health or wellness question you'd like answered, simply follow our Instagram and shoot a message to @thornehealth. You can also learn more about the topics we discussed by visiting thorne.com and checking out the latest news videos and stories on Thorne's Take 5 Daily blog. Once again, thanks for tuning in and don't forget to join us next time for another episode of The Thorne Podcast.