What's the Deal with GLP-1s?

Emily: [00:00:01] Hey, Perry. How are you doing?

Perry: [00:00:03] I'm good. Emily, nice to see you.

Emily: [00:00:05] Nice to see you. Okay, today we are talking about GLP-1s. I'm going to ask you some questions. Do you know anyone using a GLP-1?

Perry: [00:00:13] Well, wait, I've never heard of this. What is it, GLP? No, I'm just kidding. I'm kidding. Uh, yes, of course I know people on GLP-1.

Emily: [00:00:21] Do you know people using them off label?

Perry: [00:00:22] Yes.

Emily: [00:00:23] Do you know people who are using other people's GLP-1 from their refrigerator?

Perry: [00:00:28] Yes.

Emily: [00:00:29] Do you know people who are microdosing GLP-1s?

Perry: [00:00:32] Yes. Yes.

Emily: [00:00:33] Do you know any weight? Do you know anyone who is microdosing GLP-1s so they can focus better at their tech job?

Perry: [00:00:41] Okay, you got me there. I will I will take a drink.

Emily: [00:00:44] I'm a yes on that one.

Perry: [00:00:46] Wow. Uh, I want to hear more, but it might have to happen offline.

Emily: [00:00:53] I'm Emily Oster, I'm an economist and a data expert.

Perry: [00:00:56] And I'm Perry Wilson. I'm a medical doctor.

Emily: [00:00:58] It's Thursday, March 5th, 2026. And this is Wellness, Actually.

Perry: [00:01:03] Because you're getting a staggering amount of health and wellness information nowadays from every source imaginable. And some of it is awesome.

Emily: [00:01:11] And some of it is, well, actually, bullshit. Fortunately, we're both people who know how to read studies, how to parse the data, and can tell you what's worth thinking about and what you can safely ignore.

Perry: [00:01:25] But before we dig in a note that this podcast is for educational purposes and should not be construed as medical advice. We don't know your unique situation, so talk to your doctor for personal health decisions.

Emily: [00:01:35] This week we're asking what's the deal with GLP one? And you will get our highly official thumbs up or thumbs down verdict. And then we'll get to your question of the week. But first, let's do the health news roundup after the break.

Emily: [00:02:01] All right, Perry. So, doctor Mike from the internet, uh, offered RFK Jr $100,000 given to the charity of his choice to appear on his podcast. Would you take the $100,000? And what do you think about this?

Perry: [00:02:18] Oh, my God. I would take $5 to appear on Doctor Mike's podcast. I met doctor Mike. I like doctor Mike. Um, he is actually one of these influencers who generally seems to have his head in the right place in terms of, um, science based medicine and things like that. And so I think RFK would be, um, actually quite unwise to sit down with him and have a conversation. I think this is sort of a social media stunt a little bit. It gets some attention. Um, but I'm here for it. I, you know, I like people like this sort of fighting fire with fire in this space. Uh, so good on you, doctor. Mike. He's not going to take it.

Emily: [00:02:56] So I actually had a different reaction to this, which is twofold. One, I do like doctor Mike very much. I would also be on his podcast for nothing. But one worry I have is that when you platform somebody, you platform them, you let them say the things that they think. And in a lot of what RFK thinks doesn't make any sense. And also, what's the charity of choice? Is this going to mean doctor Mike is donating to the anti-vax alliance? That would be some guardrails.

Perry: [00:03:23] That's a great point. I mean, I regarding platforming, he's the the head of health and Human Services. He's got an adequate platform at this point. But you're right. Yes. He could definitely pick a particularly loathsome charity in this case. Let's stick in terms of health news with the government. Interesting confirmation hearing for Doctor Casey Means, who's being considered to be Surgeon General. At the time of this recording, there has not been an official vote on whether she would be approved to become Surgeon General. Doctor Means is an interesting character firmly in the wellness space. Just for those of those who don't know who she is. She graduated medical school from Stanford and then went to an ear, nose and throat residency program, which she never completed. So the way medicine works or doctoring works is you go to med school and then you do an internship and residency, which is sort of a supervised period where you're under the supervision of a senior doctor, and then you graduate, that you take your board exams and you become board certified. She dropped out about six months prior to graduation of from the ENT program, which is particularly odd. According to her book, she did it because she became disillusioned with modern medicine and the sort of, you know, culture of of treating disease and not preventing it because of that narrative. She's sort of become a darling of the alternative medicine space, you know, someone who is deeply entrenched in like the evil world of medicine and escaped. There's an interesting article in Vanity Fair which interviews some of her co-residents and a former chair of ENT who actually say she dropped out because of stress. So there's a little bit of retconning potentially going on here. I want to get your impression on her, but I need to know how you'll respond to this little bit of audio I found. This is not from her confirmation hearing. This is from a podcast, but I'm going to play you some Casey means audio to get your reaction.

Casey Means: [00:05:23] The more specialties we invent in healthcare, the sicker we're getting, the more drugs we prescribe in the United States for these different chronic illnesses, the increase in the rates of these diseases. So the more drugs for the diseases, the higher amounts of these diseases we get, the more specialties, the more diseases literally, the more research that we publish on these diseases, the worse the diseases are getting.

Emily: [00:05:52] Well All right, Perry. So first of all, I think she's, uh, confused about reverse causality. Uh, that's probably a little more technical than you were hoping to get, but it is.

Perry: [00:06:04] That is exactly what I was hoping to get.

Emily: [00:06:07] We do more work on a disease when it is worse. But I think to conclude that it is the research that we do on the disease that makes it worse is perhaps the wrong direction, as opposed to when there's more of a disease. We do more research on it. So I don't think the causality goes the direction that she thinks.

Perry: [00:06:23] It's one of the stupidest takes I've ever heard from someone with an MD after their name.

Emily: [00:06:27] It's a stupid take. It's on the stupider side, I agree. However, I will say that I feel like there's been a lot of credentialing of doctor means and saying she didn't finish her residency and blah blah blah. I am much more concerned about the things she's saying than whether she completed this particular component of her training and if she were saying very sensible things, which made sense and were consistent with science. The fact that she left her residency after with six months left. That's sort of that's kind of her business. My much bigger concern is that a lot of what she's saying does not comport with the science that I think the idea of having someone who is America's top doctor, which is one of the ways you think can think of the surgeon general, to have that person be unwilling to say that vaccines are a good idea, and to be unwilling to say, as she was in the conversation, to be unwilling to say, that the flu vaccine reduces flu mortality. I mean, that just feels like, really, can we do that?

Perry: [00:07:30] Yeah. And the the sort of refrain that she had, which was obviously prepared, was like, oh, well, you should talk to your doctor about this. This should all be a discussion between a patient and a doctor. You know, I'm not saying it doesn't work, but you should discuss with your doctor. It's not my place. And it's like, no, no, no. Like, actually, when you're the surgeon general.

Emily: [00:07:49] That's your place. That's totally.

Perry: [00:07:51] Your place. Your place? This is what you're here for.

Emily: [00:07:54] Ah, okay. Well, we'll see what happens there. All right. Last thing we want to talk about was a new study of football players, which is showing multiple neurocognitive deficits in general in this large sample of football players with dose response effects based on years of play, which is just a fancy way of saying the more years people play, the more neurocognitive deficits we are seeing. I did not find this study very surprising. We have a lot of evidence that repeated concussions, which is probably a lot of what's going on here, or even sort of moderate forms of head trauma that do not elevate to the point of a concussion, that those can have long term effects. But I'm curious if you had a different take on this.

Perry: [00:08:44] No, this is a nice study. 4000 football players, um, you know, from high school players on up. So this wasn't just restricted to NFL players. And as you say, consistent with a lot of prior data. And I love football. Like I love watching football. I have been an Eagles fan for a long time. I mean, I didn't love it this year particularly, but but in general. But it is hard for me to kind of see this data come out over and over and over again. And it's clear that something is happening here and it's like we're all doing that. Um, what's that meme of like, I don't know, it's like a rodent or something who just kind of like, looks like looks to the side, like, am I going to say anything? I don't know, do you guys know what that means? Is I don't know. It's it's like, are we going to address this or are we just going to kind of be like, okay, this is how football works? Because it seems like this is how football works.

Emily: [00:09:39] It is how football works. I mean, I think if you're looking for a sort of middle of the road solution from a smart person, I don't know. Do you remember Chris Nowinski, who we went to college with. Yeah. Yeah. So Chris runs an organization that studies concussions in football and tries to ameliorate this problem by, for example, not encouraging people to not have tackle football before the age of 14, so to say, hey, if there's a dose response, let's limit the amount of time kids are actually having contact in football, and then sort of maybe make some changes to how college football is practiced. So there's less head injury. So Chris is doing really, really interesting work. We can put a link in the show notes to his organization.

Perry: [00:10:26] I love it. That's awesome. My son did flag football for the past couple seasons. He's 13. It's super fun.

Emily: [00:10:33] My kids hate sports, so that's, uh, not a concern for me, but I know that it is for some.

Perry: [00:10:39] When we come back, we will ask, what's the deal with GLP-1?

Emily: [00:10:48] All right Perry. GLP-1s. So I want to set the stage here a little bit because I think that there's a kind of GLP 11.0 conversation that people can hear, like what are these? Do they work for weight loss? And we will touch on that. But I think at this point, this is so ubiquitous that people probably don't want to hear like GLP ones are effective for weight loss. I actually want to focus most of our conversation. If you're up for it, on thinking about the sort of 2.0 questions. So if people have lost weight, what about weight regain? What are the other things this might work for? What are the big concerns people have? What about the long term effects? There are some interesting economic questions which I'm dying to discuss.

Perry: [00:11:29] I love it, this is not freshman year anymore. Welcome to senior seminar.

Emily: [00:11:33] Exactly. Senior seminar, GLP one. Okay, but before we get to or maybe as part of senior seminar, can we talk about the Gila monster? Is it "G"ila monster or Hee-la monster is my first question. And can you tell me why it's such an important animal?

Perry: [00:11:48] I say Gila monster. I don't know if that is correct. You can write to us at wellness and correct everything we say. It is important. This is so interesting. So GLP one is a substance produced by your body and has been known since the 70s, and even its effects were known in the early 80s. So they took people and they gave them infusions of human GLP one. And what they found is that their gastric emptying really slowed down and they reported more satiety. So they weren't as hungry. But there was this problem, and that's that GLP one that your body makes has a half life of about a minute. And so as long as it's directly infusing into your vein, you don't feel hungry. But once you disconnect the IV, you do. So not a viable product for weight loss, obviously. And that was the state of things for ten years or so. And then we get to a weird lab at the NIH, a guy named Jean-Pierre Raufman was working in, uh, John Pisano's NIH lab testing venoms of various venomous animals. This is one of those examples of basic science. They had no idea what they were looking for.

Perry: [00:12:59] It was just like venoms. Interesting. We should know more about venom. And. Great. This guy. Uh, raufman job was to extract venom from the Gila monster. And he noticed that when he injected this venom into mice, it did weird things with their blood sugar and their pancreas. He wasn't sure what it was. In 1992, a scientist named John Ng isolated the protein in Gila monster venom that was causing all these blood sugar issues. It was called Exendin four, and that was developed into a drug called exenatide or Byetta, the first GLP one drug, which was FDA approved. Do you want to guess when? 2005. This is not new science. Um, but what was amazing about the Gila monster venom is that protein in the venom or that peptide in the venom looked like human GLP one bound to the same receptor as human GLP one, but it didn't break down in the blood in a minute. It broke down over the course of about a day, and so you could get away with injecting it, or the cleaned up variant that was eventually produced called exenatide once a day. And all of a sudden this was a viable product.

Emily: [00:14:09] So I just want to be clear, this is a peptide. So for people who listen to the earlier episode on peptides, this is an example of a peptide that is approved, not like the Wolverine stack. So go back to that episode for context there. Yeah. So okay, I think one interesting follow up question before we get to some of these details is actually the question of why. Now we're discussing this. So if 20 years ago we developed this venom, why is it now that we are seeing so much more of this, which feels like it's kind of come up in the last three years. So what is is there another science breakthrough that is more recent?

Perry: [00:14:47] Not really. It's been just kind of a gradual as these things kind of go like once the class is discovered, it's like, okay, this class of chemicals is discovered, there's iterative improvements over time. And basically the improvements have been two things. Number one, increased potency, which means that they've developed peptides that bind a little more tightly to the GLP one receptor in our cells and to increased half life. So where semaglutide, which also some people say semaglutide, but I say semaglutide or Ozempic came along with a once weekly dose because it was stable in your blood for a much longer period of time, had a much longer half life. That's where you start to get people willing to think about this for treatment of obesity. Most people without diabetes aren't comfortable injecting themselves once a day with a product, and in fact, even people with diabetes don't. No one loves injecting themselves, right? And so, so once a week was a thing, there was another Milestone in the obesity literature, which was this magical 10% weight loss threshold, which had always been the like, arbitrary marker of is this drug successful for weight loss? And Beda, the first GLP one was not. It led to some weight loss, about 2 to 3% over the course of a year. But it just wasn't potent enough. And it was really and still is used for diabetes control, blood sugar control. You got the first greater than 10% weight loss effect with liraglutide, which came out later, and that sort of set off the arms race that we have now, where you're just inventing drug after drug that are more potent and more potent. And of course, like the most recent trial, Lilly's new drug, which I can't, I can I can even say.

Emily: [00:16:22] Don't even try.

Perry: [00:16:23] Retracted had a 28% year on year weight loss, which is insane.

Emily: [00:16:31] Okay, so right now we find ourselves in a moment where the two medications that people are most commonly using for weight loss are Wegovy and Zepbound. Wegovy is semaglutide. It's the ozempic equivalent, but prescribed for weight loss. Zepbound is trizepatide. It's the Mounjaro equivalent, but prescribed for weight loss. Both of these lead to something between 15 to 20% weight loss in the first year in the trial data. They are both served through a weekly injection that people give themselves. And the next thing that's coming is a set of we're going to keep seeing innovation here. The next thing that's coming is an oral form from Eli Lilly, which has a slightly lower amount of weight loss. But my guess is that the uptake will be very high because people would rather take a pill than have an injection. So we really find ourselves in a moment. This is kind of the the Ozempic 1.0 where these medications are incredibly effective for weight loss. They're much more effective than pretty much anything we have had in terms of diet and exercise. They just work really well and more and more things that are developed are going to make them work better. To the point, I think you discussed the latest trial with 30% weight loss. People are starting to have a conversation about like, what's too much? Like how much weight loss is is too much. Weight loss like 30% is a lot in a year. And so we're kind of at the point where probably it's almost enough. Although people always like more. But I think it's very clear that these are effective for weight loss. And that is like the science is done on that particular piece. A next interesting question is what about the other benefits? So before we get into like the things we're concerned about, these were originally prescribed for diabetes. They are effective for weight loss. But we're starting to see all kinds of claims like this is good for kidney disease. It's good for cardiovascular disease. This is good for, you know, I don't know like.

Perry: [00:18:28] Cancer.

Emily: [00:18:28] Cancer for everything. I mean, which of these things are best supported? I'm going to ask you because I think one of the best supported one is the kidneys. And you are in fact, a kidney doctor.

Perry: [00:18:37] Yeah. All these off. Kind of off target effects. And I think it's good to think about the non non-diabetes effects based on whether they are related to a reduction in weight or are they something else entirely. So let's take cancer as an example. So there have been several studies that have shown that the use of these drugs reduces the rate of obesity related cancers. So the classic obesity related cancers, cancers that are driven by some of the hormones that come from fat and stuff like that are like breast cancer, cancers of the GI tract, colon cancer. And the rates of those things do go down. But it's plausible. We always talk about biological plausibility that the reason they're going down is not because these drugs magically kill tumor cells, it's because people lose weight. And weight is a risk factor for the development of these types of cancers. That's a similar mechanism for like a reduction in blood pressure. For example, if you lose weight in any way, your blood pressure goes down. Same thing for kidney disease. Broadly speaking, the more weight you have, the more metabolically active tissue you have in your body, the more work the kidney has to do. And in general, if you can give the kidney less work to do, it's happy to not have to do as much, and they can kind of last longer. I think it's probably similar for cardiovascular disease as well.

Emily: [00:19:50] So I will say that I think that in some of these trials, when they're looking at other kinds of cardiovascular disease and so on, there's sort of some discussion that maybe the effects are larger than you would expect based on weight loss alone. So they're sort of trying to do a kind of calibration and then say, well, maybe it's it's like a lot of the weight loss, but then there's something that you get more. Although I think that's obviously a very hard thing to sort of separate fully in the data.

Perry: [00:20:18] Yeah. And it relies on some assumptions of like, you know, how many pounds of weight is equivalent to how many millimeters of mercury, of blood pressure that are always like a little bit hand-wavy. So that's all true. Like the epidemic of obesity in our country and around the world is driving much of the chronic disease epidemic. It just is. And so anything that impacts obesity, whatever it is, is going to reduce the rates of those diseases. That's cool. But what always kind of gets me interested and I want to ask you this, Emily, are the things that really can't plausibly be related to weight loss. So what do you think about, like the fact that people report less smoking or alcohol intake or gambling like this stuff?

Emily: [00:21:00] Yeah, I mean, I think so. My sense is of those things. The one that is most strongly supported in the data is alcohol, partly because that's where we've studied the most, and partly because that's an activity that most people engage in. There's a lot of reports in both the data and just out in the world that people's interest in alcohol declines as a result of this and that other, you know, their interest in smoking, their interest in all these other kind of maybe what we consider vices goes down. One interpretation of of the way these medications work is that there's something about sort of almost like sort of self-control, like inhibition value. And I mean, this is consistent with when you talk to people who take these medications. And I have not, but I've talked to a lot of people. One of the things that is very common for people to say is like, it turned off the noise. Like my my head was full of food noise and I was always thinking about food, and I was always thinking about that. And this made me think about it less. And if you think about the way that a lot of people feel about alcohol or smoking or whatever, it is also that noise, it's like, I feel the noise. I want to have a drink or I feel the noise, I want to have a cigarette. You can imagine that whatever is that mechanism, it might work there. Similarly, I know people who take this for for focus, who microdose like zepbound for focus.

Perry: [00:22:14] Yeah, talk to me about that. I've never heard that before.

Emily: [00:22:17] I don't know. The guys in Silicon Valley do a lot of weird stuff. Perry. And one of the things in people's is like, it really helps you focus. It helps you not be distracted by whatever food, noise, alcohol, noise, smoking, noise, other kinds of noise. Certainly I would not say that we have science or data or evidence that supports that piece. But putting all of these things together, it does feel like maybe there's something in there. There's something about the way this is interacting with people's brain chemistry that could be consistent with some of these effects. Actually, there's someone um, I believe there are some people thinking about experimenting on providing people GLP ones when they leave prison. And one of the outcomes they would look at is recidivism. And one interpretation of that is that basically, if you could turn down people's impulses to engage in alcohol and drugs and so on, they might actually be less likely to return to prison.

Perry: [00:23:10] Wow. So fascinating. Totally fascinating.

Emily: [00:23:13] That's interesting. Again, this is like we're on.

Perry: [00:23:16] Of course, we're way out there.

Emily: [00:23:17] You know, we're way out there.

Perry: [00:23:18] There is plausibility here, though. I mean, one thing that people know, I think at one point people know that GLP ones decrease gastric emptying. So that just feeling of having a full stomach, it really does seem like that is not everything here. Um, I did a quick review of where GLP one receptor is found in your body. So you know what kind of cells express these receptors in high levels. And yes, they are throughout the GI tract and pancreas and things like that. But right up there in terms of organ systems is the brain. So your brain has these receptors. We do know that these peptides can cross the blood brain barrier. And once a drug can cross the blood brain barrier, and once you know there's receptors on your neurons for that drug, like it kind of opens the door of anything being possible to some extent. Right? So all of these things are definitely plausible.

Emily: [00:24:06] So one thing people wonder about sometimes is when you're on these and you lose weight, is it quote the same as losing weight in other ways? Is it literally just this makes you eat less and you eat less, and then you lose weight, like commensurate with the way you would lose weight, you know, if you just literally ate less. Is there something more than that? Or is that kind of the whole business?

Perry: [00:24:26] Oh, this is such a good question, because so much of what I see online. There is. There is like an anti GLP one current that that is under there. And typically the arguments do go something like this. Like this is not natural. Like this isn't the real way to lose weight. And and because it's not the real way to lose weight, it does these certain bad things. And I think the one that you hear about the most is probably muscle loss. And people come and are like, oh no, you're not just losing fat, you're losing muscle. And Emily, I know you've looked into this, so I will ask you, is it true that if I lose weight through other means like diet and exercise, that I only lose fat and don't lose muscle?

Emily: [00:25:08] That is not true. Perry, when you lose weight in any way, you lose both fat and muscle. And some of that is like sort of intimately linked, because one of the things your muscles do, actually the main thing for most of us are muscles are doing are moving us around in the world. Yes. And so if you are heavier, your muscles are moving more stuff. It's like you're constantly wearing a weighted vest. And when you lose weight, even if you just lost fat, your muscles would be like, great, we don't have to have so much of us anymore because we aren't moving around so much weight. And so there is like an inherent feature of losing weight where you are going to lose some fat and some muscle, and if you have a lot of fat, you will lose relatively more fat. But no matter how you lose weight, you are losing some muscle. And that is also true on Ozempic. And actually, the study suggests it's no more true on GLP one than it is with other kinds of diet. Like you just you lose some fat and some muscle.

Perry: [00:26:01] Yeah. And typically about 30 to up to 50% of weight loss can come from muscle. Regardless of what the weight loss is. There is a little wrinkle here that I don't see brought up often, but I'll say it because we're in senior seminar and that is that. The way that muscle mass gets assessed typically in these studies is through a Dexa scan, which is sort of a, um, think of it like an X-ray, but you can see muscle tissue.

Emily: [00:26:26] We could do a whole episode. Influencers love a Dexa scan.

Perry: [00:26:29] Oh, interesting. Okay, so Dexa scans don't actually distinguish between muscle and what's called lean mass, just like non-fat non-bone mass. So they sort of assume that, like, everything that isn't bone and isn't fat is muscle, which is obviously not true. You have like organs and stuff like that, but it's it's more than that, which is that fat infiltrates muscle, and Dexa scans cannot determine how much of your muscle is infiltrated by fat. It just looks like more muscle. You can think of this as like the marbling of a steak, right? Like, if you fatten these cows, you get nice prime rib and things like that. And it's really tastes delicious, but it's actually bad for your muscle quality. And so we don't it may be that some of the fat loss is happening within muscle, which is almost certainly a good thing. But yes, you're going to lose muscle if you lose weight, no matter how you lose weight. So, Emily, let's say I don't want to lose muscle, or at least I don't want to lose as much muscle as possible. Can I prevent this or am I doomed?

Emily: [00:27:29] So one of the totally fascinating, like knock on impacts of the Ozempic craze is the strength training craze. So the idea that you sort of like all of a sudden you're on the GLP one for weight loss, but now you need to do strength training, and that's actually not crazy. If we think about like how do you retain and build muscle, you retain and build muscle by exercising, and in particular by exercising in a way that, you know, cardio. Yes, but also like by lifting stuff. And so there's a kind of combo here where you take the GLP one for weight loss and you exercise for muscle retention, which tends to be a good combo. And interestingly, many people report their willingness to exercise and like get up and go to the gym is greater when they're on a GLP one. Getting back to potentially some of the stuff that we talked about before around sort of impulse control. Um, the other thing is prioritizing protein, right? So like so much of what's happening when people are on GLP one is they eat less food. Like fewer calories. And but making sure that those fewer calories are actually. Like you're maintaining protein the amount of protein shouldn't change that much. Whereas the amount of other things should change more and kind of thinking about that balance. So there's still like a need to think about diet and exercise. Even if the GLP one is acting. I will say I was at an influencer dinner at some point a few months ago, and we can get into the economy later, but I think restaurants have really adapted to this because all they serve was protein, like it was just exclusively protein. There was like one tiny thing of French fries on the table and like, I like carbs.

Perry: [00:29:06] Yes, you are a carb queen.

Emily: [00:29:07] I was sad, I was sad about. I was like, where's where's the bread service? But the bread service is over at fancy restaurants.

Perry: [00:29:15] Yeah, yeah, it's just egg white service now. And protein water.

Emily: [00:29:19] Tuna and egg whites exclusively. Okay. So that is the kind of, I think, big picture of like sort of what happens initially when people are on this and what are some of the other things that could work for. I think we should get into the things that people raise about that are more concerning. The first of which is weight regain. The question of do I need to be on this forever? Yeah. And I will say in the trials, the evidence is pretty sharp that when you put someone on a glp1, they lose 20% of their body weight, you take them off their glp1, they gain back about half of their body weight, at least in the trials. So is this a sort of is this a life sentence and is that a problem? I guess is my secondary question.

Perry: [00:30:04] I think the data is quite clear. But like, you know, part of me as a doctor is like, well, we have lots of medications like this. Like when I treat someone for hypertension and I put them on a blood pressure pill in general, the expectation is like, yeah, if you stop this blood pressure pill, you will your blood pressure will go up again. Like that's your there is some constitutive effect there. One of the things I've seen online from influencers, though, who are kind of anti GLP one is like, oh, but if you lose weight through lifestyle change and changing your habits, then like you'll have that forever. But with GLP one you're you're stuck for life. And you know this data as well as I do, Emily, like.

Emily: [00:30:44] That's the stupidest fucking thing I've ever heard.

Perry: [00:30:46] Like the data on maintaining weight loss with diet.

Emily: [00:30:52] Is literally awful.

Perry: [00:30:53] Abysmal.

Emily: [00:30:57] For me, like the stupidest piece of this discussion because it's sort of presumes like, well, of course we had a way before for people to lose large amounts of weight and keep it off with diet. And now, you know, we're not using that anymore. It's like, actually, no. Yes, it is possible to lose weight with diet. And some people do. And I know because they show up in comments when I talk about this and they're like, I lost 300 pounds doing yoga and walking around the block one time, it's like, that's super for you. But for most people, that actually isn't effective. Most diets work for a little while and then people gain the weight back. It's very, very consistent. And so I'm not sure this is really any different than that. Nor do I think it's very different, as you say, than something like a statin, which people go on and then they stay on forever. And which, by the way, you might be able to get off after you're on your GLP one because your cholesterol might improve. So that's another thing to think about.

Perry: [00:31:50] Well, yeah, I was thinking the same thing with my blood pressure pill. I was like, actually, they might be able to come off if they start the GLP one, the trials. One of the reasons we even have this data is because most of these trials last basically a year. Some some go up to like a year and three months or so. But that's the extent of the data. And so we just don't know with that degree of fidelity, like what, ten years on a GLP one in terms of weight loss looks like there's observational data to that effect because the GLP ones have been around for so long. But the randomized trial data is limited in scope. What is interesting is how people in the real world are kind of handling this. So yes, they lose a lot of weight. They get to await, they're happy with, and then they're like, okay, I'm good. And what I've found with patients that I've spoken to is generally not like, okay, I'm going off glp1, but people are doing this thing that often gets that's called microdosing. So what do we know about microdosing? Is this the answer? Like, yeah, you'll be on it, but you're only going to be on a little bit. I don't think we have any idea.

Emily: [00:32:49] And I think the reason is sort of interesting in terms of the, of the science. So think about the kind of who is running the trials of these. The people who are running the trials are the people who are making the drugs. Right. Novo Nordisk, Eli Lilly, the makers of the drugs, run the trials, and they trial their drug at the dosage that they are going to sell it at, because that is what the FDA tells them to do. That's how drug trials work. They don't usually run trials of like, and here's exactly how you're going to do it in the real world. But in the real world, when people get to this, most of the doctors I know who are using this will do. I'm not sure they'd call it microdosing. They call it a maintenance dose, right? That we're like, we started with a low dose. We go up to a dose in which you're losing weight in a consistent way. You get to the weight that you would like to be, and then you drop down the dosage until you get to a point where you are maintaining that weight and that feels comfortable. And that's how this is actually operating for most people in the real world. I'm not sure we're going to see trials of that in the short run, because I'm not sure who would who would run them. Right. So I don't think Novo Nordisk is going to run that kind of trial. Yeah, somebody will eventually. But I think it's and it's also just so like in an ideal world, it's sort of so titrated. One of the concerns, I think, is that people are titrating it themselves, whereas a much better thing would be to titrate under the supervision of your doctor, not to just like take half your dose, which is my sense is what people are actually right.

Perry: [00:34:14] And a lot of this has to be done actually through compounding pharmacies, which we've talked about in a prior episode, has potential safety concerns. The Ozempic pen has a little clicky dial that you can turn, which does allow you to change dose. Um, my understanding is that the Zepbound pen does not. So the only way to kind of microdose that is to break the thing open and like, don't do that. That's that's a bad idea. So you're kind of going outside the box a little bit here. But I agree I think this is probably what happens. Like eventually we'll get to a point where, first of all, there'll be oral drugs and this will be the kind of thing that you do. Probably take some lowish dose, probably for an extended period of time, unless you're want to gain some more weight.

Emily: [00:34:59] Yeah. Okay. So it is a long term medication, but maybe the right frame is this is a long term medication like your statin, your blood pressure medication and not a diet like the time that you tried to lose weight on the all protein diet for six months and then gained it back, which is, in fact, how people interact with diets. Um, okay. The second big concern is just are there side effects, which there are. I think it should be very clear. Like this is a drug. It has side effects. The main side effect people complain about is nausea and other gastric problems. That is a I think of just a that's a feature. I don't know if it's a feature or a bug. It's a very common side effect. What about some of these more serious things. Pancreatitis, depression.

Perry: [00:35:46] Okay. Probably should go through very quickly. Like one by one. Pancreatitis. Yes. Rare case reports probably associated with these drugs. We know they act on the pancreas. In fact, that Gila monster venom. When a Gila monster bites a mouse, it causes an acute pancreatitis. So I buy it? Yes. Rarely. But. Yes. So people need to know, like symptoms of that are a deep and painful burning in your upper part of your stomach. Like you'll know this is. This is bad. When it's happening. You definitely want to get checked out. Okay. The depression suicide thing. This is really interesting because we've talked already about, you know, the ability of these drugs to potentially modulate reward pathways in the brain. And you framed it differently, Emily, for the first time. And I'm it's like I'm still kind of grappling with the way you frame this. So so the way I hear people frame this is like, oh, it takes away your desire to eat. It takes away your desire to smoke. It takes away your desire to drink alcohol. But like what it's doing is it's just it's kind of all the pleasure, pleasurable things that your brain wants.

Perry: [00:36:48] It just kind of cuts that off. And then like, are you joyless? Is there no is there no hope in the world? And if so, might it not increase depression and suicidality? Rfk Jr himself has raised this issue, and I'll just point out that the current best data is from a meta analysis of 27 randomized controlled trials, including 32,000 people looking at the rates of suicide and self-harm from these drugs. And there is no difference in suicide or self-harm events between placebo and these drugs, so I do not think that is real. And one of the reasons I like the way you reframe this for me is as opposed to saying like, oh, it cuts the reward pathways. Like you don't get the like high of eating food or the high of drinking alcohol. You've reframed it as like it's not ending that thing. It's giving you this like, um, it's giving you control. It's giving you more focus, which is I kind of like it. I mean, I don't know if it's true, but that is a different way to think about it. That might explain why you get less drinking, but not suicidality.

Emily: [00:37:48] I don't know, I mean, I think that is a way that I have heard people try to describe to me what this is like, which I think is a potentially interesting organization of some of these facts. But I don't know. Again, it's like it's always hard to get inside people's brains.

Perry: [00:38:04] It is. When we talk about enjoyable things that your brain likes to do, something that always comes up is sex. So what do we know about sexual effects of these drugs?

Emily: [00:38:15] Relatively little. Um, you know, there are people who will say like this limits your desire to have sex. I don't think there's a lot of evidentiary support for that. What I will say is there are some real issues that people in long term relationships grapple with when they go on these medications, particularly if, you know, there's New York Times actually said a series of very interesting stories about couples where one person has gone on a GLP one and they sort of said, well, you know, our life used to revolve around going out to dinner and and drinking together and hanging out, and, and now this person doesn't want to do those things anymore. And so, you know, maybe you you do want to have sex, maybe you don't want to have sex. But there's another piece of of it's not about a lack of interest in a physical relationship. Or maybe it is, but it's also about changing the relationship. And I actually think that's a really important part of this for a lot of people, that eating is a huge part of our of our lives. And if you change things so you aren't going to eat in the same way, and you are in a relationship with another person and they're not going to change that, and your body is going to be going through a lot of changes. Like that is just an adaptation that people should expect and and should, you know, think about as part of this. I think it's less about sex and more just just about, you know, when you change something totally about yourself and your relationship, it changes and you have to adapt. And relationships are hard is my fundamental feeling.

Perry: [00:39:46] Yeah, indeed. I agree there's sort of a disturbing lack of data on this. As I was looking in, I'll just say there are like ten times as many studies on male like impotence and anorgasmia from GLP ones than there is on female. It's like, all right, researchers like get with the program here a little bit. Women are more likely to take GLP one and are more likely to lose a greater percentage of body weight on GLP one than men. Clearly this needs to be looked into. I agree, there's nothing terribly compelling. I did find one study that was an observational study looking at rates of a clinical diagnosis of anorgasmia, the inability to have an orgasm, which did find that compared to women, not on GLP ones, those on GLP ones had that diagnosis code about twofold. More often, it's a very rare diagnosis code to get, because most people don't talk about this with their doctor in the first place. But that rate was similar to women taking metformin, which is another drug for diabetes. So this is probably related to the underlying reason that the woman is taking the GLP one, as opposed to the GLP one itself. But you know, more data. I'd like more data here.

Emily: [00:40:56] Who doesn't want more data on women's sexual function as opposed to men's sexual function? Where we're really we're good. Thanks. It's enough data. We know everything. We got it. We're fine. Um, okay. I think there are some interesting social and regulatory questions here, or maybe just social questions that we should make sure that we hit on. Uh, last thing that I, I will say I'm bringing up in part because this is the first thing my father ever asked me about Ozempic. He was like, have you heard of Ozempic face? And then he was like, blah, blah, blah person that I know has it. And I was like, yes, I have heard of that. Um, so, uh, Perry, have you heard of Ozempic face?

Perry: [00:41:35] Oh, I've heard of Ozempic face. I've heard of Ozempic butt. Um. Yeah, yeah.

Emily: [00:41:40] So Ozempic face. My sense is that when you lose weight, your skin takes some time to tighten back up. Which. Or maybe it doesn't tighten back up and that you lose a lot of weight in your face then or your. But it will be saggy. Yep. It doesn't matter if it's on a GLP one or in some other way.

Perry: [00:42:00] Yeah, we don't have that magic bullet that only makes you lose fat like around your belly, but leaves shredded abs behind Like when you lose weight, your body consumes fat. Fat is there to be a source of energy when you don't take in enough calories. And that's what GLP ones do. They make you eat less so you expend more calories than you're consuming, and so your body breaks down fat as well as some other tissues, as we discussed, to recapture that energy. And it'll take fat from everywhere. What Ozempic face is in, medically speaking, is midface volume loss. That's what the plastic surgeons call it. So that's sort of, uh, cheekbones and cheeks gives kind of a sunken appearance. And you're right, this is what happens with all forms. Yep.

Emily: [00:42:43] That one is for the socials.

Perry: [00:42:44] Emily, for those of you just listening on the podcast is making kind of a fish face. Um, this is what happens with all forms of weight loss. I think the reason it's in the zeitgeist now is that we just never had effective weight loss that was working for the masses. So. So where you will have seen this before is people getting gastric bypass surgery, which was like before the GLP one was the main way that people could lose a significant amount of body weight, but that's a big surgery. But if you think of, like Al Roker before and after he had gastric bypass, before and after that, he looked very different. He had mid-face volume loss. We didn't call it Ozempic face back then because it didn't exist. This is just weight loss face. It is real. In fact, the American Academy of Facial Plastic and Reconstructive Surgeons reported a 50% increase in facial fat grafting procedures in 2024. So people are thinking about it totally.

Emily: [00:43:36] Okay, I think that's a really good segue, because I am very interested in the knock on economic effects of these medications.

Perry: [00:43:44] Oh, I love when you bring your economic doctorate into this discussion. What's going to happen?

Emily: [00:43:49] So I'm going to tell you.

Perry: [00:43:50] And where do I invest?

Emily: [00:43:51] Okay. So if I were an investor I will tell you, number one I would invest in places that do excess skin removal. I'm not kidding. I think that there is going to be a huge excess demand for skin removal procedures, because if people have been overweight for a very long time and you lose, if you lose 300 pounds, you end up with a lot more skin and people can find it. They may not like how it looks, but also it can be uncomfortable and difficult to navigate. And there are procedures that will remove excess skin. And I think that that is an incredible growth area. And we will see a growth in the kind of medspa skin removal surgery situations.

Perry: [00:44:33] Okay. Those are big surgeries. That's no joke.

Emily: [00:44:35] I realize that and I but I still I'm still going to go.

Perry: [00:44:39] Okay.

Emily: [00:44:39] Getting there. Okay. So that's one place.

Perry: [00:44:42] I'm wondering about. Like our food industrial complex, right. Like, I walk down the supermarket and there's, like 80 different cereals. Like, are they scared? Is Kellogg's like, uh oh.

Emily: [00:44:50] Oh, I think they are. Yeah. So I think there's like two interesting sort of places that that may be affected by this. One is like the snack food complex, right? If you think about what is going to go from people's meals, I think snacks are likely to go some. And so I think we are already seeing impacts on snack foods. We're already seeing restaurants think about, hey, can we lower the portion sizes, right. Like for a restaurant. That's good. You'd rather give people smaller portions because it's less expensive for you. And so we sort of I think we may see a little shrinking. Um, the place I think the other the growth area in the other direction is protein snacks. Right. If you think all of a sudden people are eating fewer calories, but they need a lot of protein, that's where you need your protein popcorn, your protein. You know.

Perry: [00:45:36] I'm so glad there wasn't enough protein snacks.

Emily: [00:45:40] Protein wasn't enough protein snacks. And now the David Bar is coming for you. And so I think it's a sort of protein growth carbohydrate snack decline. And so I do yeah I do think that there's some some movement in that space. I'm not exactly sure how I would invest on that or on any of my ideas. It's a good thing I don't have a lot of money to invest in my stupid investment ideas.

Perry: [00:46:00] What about medicine with a capital M, like I work in a hospital. I see patients in a clinic. Do you think that this can be transformative enough that, like, I won't have as many kidney disease patients. I won't have as many heart disease patients. I mean, people have to die of something, I guess, right? Like, eventually, maybe it happens when they're older.

Emily: [00:46:19] Yeah. I mean, that's those are much more those are much slower moving changes. I think there are also a very there's an interesting overlap there with the question of, of kind of the cost of these drugs. So these drugs are right now quite expensive. The prices have been coming down a lot, but they're still expensive. They're covered in sometimes intermittently by insurance. But one of the arguments for expansion of access to these medications, especially if we think about like a government payer, is that they will lower people's risk of other things. So you, Perry, are expensive. Somebody comes to see you. You know, it costs money. If fewer people have kidney disease because of their GLP, one actually sort of offsets the cost of the GLP one Glb1 to some extent, and depending on how big those effects are, we could see these medications, even though they are relatively expensive, and even if they stayed relatively expensive, we could see them cause overall cost savings in the health care market, which would be in part a reduction in sort of need for for doctors, but probably would be more significantly, a reduction in use of other medications. So if you are a maker of a statin, this may be sort of more bad for you than if you are someone who treats people with a heart attack, which is still something people are going to die of. Just maybe. Maybe they'll die of them later.

Perry: [00:47:37] One of the things that this ties into is, okay, we've sort of come to the point where we're like, these drugs are going to be in the fabric of our society, whether they're injectable or oral. We've said that you're going to be potentially taking them for, in some form or another for a long period of time. And a lot of people are worried about that saying like, you know, but we don't know what might happen. Right? That. Sure, they seem to be working great now, but how do we know that if you're not on it for 30 years, it causes cancer or something like that? What data do we have to either reassure people or terrify them?

Emily: [00:48:11] Yeah. I mean, I think that the short answer is we don't we can't really fully reassure people about that. You know, these first you said at the top the first of these drugs is approved in 2005. People have been on this for diabetes for a long time. We haven't seen those kind of signals, but it's not exactly the same drugs. It's not the same dosing levels. It's not for the same indication. So if you want to know what is the impact of these drugs in 30 years, you need to wait for 30 years. And you know, we ultimately like with almost any new drug, you've got away the sort of known value of the medication against these kind of long term potential risks. I actually think that sort of cost benefit calculation is always an important part of these choices, but is probably relevant to the extent that some of the usage of these medications is not for indicated purposes, right? So we are definitely seeing use of GLP one in populations where people do not need them to treat metabolic disease. Right. This is a medication that is intended to treat obesity or diabetes or complications of obesity. That is the indication for the medication. It's not a medication intended to move your BMI from 21 to 14 or 17, which is some of how it seems like it's being used, particularly in celebrity circles. And it's always hard to know who's losing weight for what reason. But there's a kind of the part of the cautionary conversation it feels important to me is the one where people are sort of using these effectively, really off label in a way that changes the conversation around what is an appropriate physical appearance for for someone. And we're kind of we lost a little bit of of what I thought was broadly a good move towards the idea that people could be different sizes and not just a size two.

Perry: [00:50:04] Thank you for saying that. Um, it's worth noting that fat has value like it is metabolically important. It is hormonally active tissue in a good way. Um, and being underweight, however you get to being underweight with this, you know, with this drug or any other way can have actual long term health consequences. And there's there's any number of studies that actually show that sort of the sweet spot for body weight in terms of longevity and especially resilience against disease. So when you do get sick, you know, being able to sort of bounce back from that is probably in the what we the normal weight range, a BMI between 20 and 25 or so. If you're pushing below that, you are starting to stress your body a little bit more. I just have to say, I have a patient who is telling me that she was taking one of these drugs to get back to her original weight. And I said, what was your original weight? And she said, 7 lbs, 14oz.

Emily: [00:51:01] Ah, that's too much. No, I mean, I will say I've started to see discussion. You know, people have started to talk about this a lot in the endurance sports community because it is of course, true if you are like a runner, that there is some value to being smaller because you're moving less bulk. But actually these medications are really bad for performance. And some of these sort of discussions I think have gotten like a little confused and also ultimately probably not very good for either people's health or in that particular case, for running fast. So if you want to run fast, this is maybe not for you.

Perry: [00:51:40] Not for everyone.

Emily: [00:51:41] Not for everyone. Yeah. All right, so, Perry, before we get to our final feelings on this, let's talk about sort of where this is going in, both in terms of the medications and in terms of, of kids. So on the question of the medications, you know, my sense is we're just going to keep seeing new versions of this come out that are better in a variety of dimensions, easier to dose oral versus injected, more weight loss, 28% versus 20%. Those are the two big dimensions. What what other dimensions are we going to see?

Perry: [00:52:11] Innovation cost. You know things will get cheaper. But but yeah I honestly I think in terms of weight loss like up at 28% I think we're done. Like you're taking a 200 lbs person and bringing them down to 140 lbs like this is probably I don't think we need to improve too much on that. So yeah, you're going to see cost differences as things come off patent. And then the orals are going to be somewhat game changing. And there may be tweaks that improve side effect profile and things like that. We'll see that. The question of kids is really fascinating. So the landscape right now is that Ozempic itself does have FDA approval for kids 12 and up. Um, it's the only one. The rest start at age 18. I'm ambivalent about this because for one thing, kids are kids. They're not just small adults. They're their own things. They're growing. And especially for kids who are growing like calories are important for that. And stunting a kid's growth is a permanent thing that can happen. So I'm very nervous about this. On the other hand, there is an argument to be said that, like, you know, the fat tissue that you add as a child does not really go away, ever. In fact, as you as you lose weight, a lot of those cells are just shrinking, not necessarily dying off or evaporating. Is it a possibility that establishing some habits with the use of a drug like this in your youth, when you're sort of forming your relationship with food, could be beneficial in the long term. On the other hand, could it be entirely harmful? Like, I am really up in the air about this.

Emily: [00:53:44] You're in a rabbit hole. Yeah. Me too, I.

Perry: [00:53:46] Am I don't I don't know.

Emily: [00:53:47] I think it's really complicated because you're right. I think our our habits, our tastes for foods, our form when we are kids. And that is an argument for forming those habits. Well, I mean, I guess my the thing I would say for sure is this should not be a first line. Like, I would really like us to think more carefully about how we can help families develop good food habits with their kids, whether that's like better school lunch programs, better supports, like all kinds of things I would like to do before we get to like, let's give everybody ozempic when they're 12, which just feels like, you know, probably there are some people who will benefit from that, and it will be good to have that as an option. But I don't want it to be the first line, and I don't think that that's a good idea.

Perry: [00:54:33] Okay.

Emily: [00:54:34] All right. Okay, Perry, we're going to end with our segment in which we give our yes or no. And I am going to insist that we call this segment Smash or Pass.

Perry: [00:54:44] All right. I'm I am on board. And for those of you from a generation that is not X, you can Google what that means.

Emily: [00:54:51] All right, so Perry GLP one smash or pass?

Perry: [00:54:56] Smash. Definitely transformative drugs will be with us for a long time. Changing a lot of outcomes. Not for everyone as you say, but yeah, definite smash for me. How about you?

Emily: [00:55:07] Yeah, I'm a smash if it's the right person. Uh, on this one, I think for some people, for many people, this is going to be a really game changing solution. It's not for everyone, but I think it's going to represent a really important part of of the health landscape in the next several decades.

Perry: [00:55:23] All right. After the break, we'll get to your question.

Emily: [00:55:30] All right, Perry, mailbag question of the week, uh, is a personal one. What is the dumbest thing or greatest thing in your fridge right now?

Perry: [00:55:41] I have such a good dumb thing. And like, for a podcast about wellness, just beep this entire segment. Don't listen to what I'm about to say, but you can get from Amazon or any other online store. Do you know the cheese powder that goes in mac and cheese? Like the orange?

Emily: [00:55:59] Of course.

Perry: [00:56:00] Yes.

Emily: [00:56:01] Oh my God.

Perry: [00:56:01] You can get a bulk of that.

Emily: [00:56:05] Perry. That's so gross. Okay.

Perry: [00:56:06] Okay. Wait. Here's what you can do with it. Hey, you can add it to your mac and cheese. It's that much cheesier. But wait. There's more. You can make popcorn, and then you can put that stuff on your popcorn.

Emily: [00:56:21] That does sound good. That's good. Yeah.

Perry: [00:56:23] You can. You can make pasta sauces out of it. Um. It's so good. It is so bad for you. Please don't do this anymore.

Emily: [00:56:30] Um, Perry, why does it have to be in your refrigerator? This is what I don't understand.

Perry: [00:56:34] So actually, it's. No, it's in my cabinet, but. Yeah, but now it's like, why shouldn't it? It's cheese. Like, it probably should be in my refrigerator.

Emily: [00:56:40] No, I don't think that stuff is cheese, my friend. Sorry to tell you.

Perry: [00:56:43] It's micro-plastics. What's the dumbest thing in your refrigerator? I'm so curious about this because Emily's like the healthy one. For those of you who don't know both of us. Um, so it's going to be like, oh, I, I got tomato juice, but it was like a normal amount of sodium.

Emily: [00:56:59] No, I like sodium. I drink a lot of sodium. Please. I drink like I put LMNT in my water in the morning. I'm like, very into sodium. We can talk about that another time. All right. I have a kind of peanut butter I really like. It's called One Trick pony. I am peanut butter is like one of my core food groups. And unfortunately they have had a jar shortage. And so the only way to purchase this online right now is in a 9 lb tub. And so I have a 9 lb tub of peanut butter that's on the fridge, though.

Perry: [00:57:30] That's a lot of peanut butter.

Emily: [00:57:32] It's a lot of peanut butter. I go through it surprisingly quickly.

Perry: [00:57:37] That's it for us today. Stick with us next week when we'll ask, what's the deal with red light therapy?

Emily: [00:57:44] Well, this actually is produced in association with iHeartMedia. Our senior producer is Tamar Avishai, our executive producer at iHeart is Jennifer Bassett. Our theme music is by Eric Deutsch and our content is for educational purposes only.

Perry: [00:57:58] If you like the show, help other people find us. Leave a rating and review on Apple Podcasts or your podcatcher of choice, and help us spread the word about the show. Don't give the TikTokers all the power. And don't forget, we want to hear from you. Head over to and leave us a question for our mailbag, or suggest a topic for a future show.

Emily: [00:58:18] We'll let the influencers have the last word.

Influencer: [00:58:21] I saw a commercial for Weight Watchers. We're doing GLP ones now, which is ozempic and stuff. That's like a karate dojo selling guns. You know what I mean? Like it's not what it is. The latest breakthrough in self-defense. Guns.