GLP-1s and the ‘Wild West’ of Wellness

Introduction

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GLP-1 Medication

0:56Here's a number that actually shocked me when I learned it. This is from a new Kaiser Family Foundation poll. One out of eight Americans is now taking a GLP-1. One out of eight. Maybe I shouldn't have been so shocked because the number is higher in my social circles. I have tried these for reasons I'll explain. But they're a strange medication, right?

1:28They don't make you lose weight. They make you not want to eat food.

1:33But then they do all these other things. They seem to protect people's heart health independent of losing weight. They're protective of kidneys, of livers. There is ongoing research about dementia and Alzheimer's. They have all these strange effects on addiction and desire. But should everyone be on these? Like, what does it mean for society to have access to drugs that regulate desire in this way? What do they mean for the sick? What do they mean for the well?

2:05I've wanted to do an episode on this for a while, but haven't known quite how to approach it. And then Julia Ballouz, who's a contributing writer at New York Times Opinion and co-author of the book Food Intelligence, and also was a health and science reporter with me back at Vox. She started doing a lot of reporting on GLP once, and she's written a lot of great pieces on them, including doing some really interesting survey work. One of the survey questions that really stuck with me was if people on them, more than 60% would continue with them, even if they didn't help them lose weight.

2:36So why is that? Well, I wanted to ask Julia. She's someone who I really, really trust to look at the science of these questions in the most rigorous way possible, and also to look at the experiences patients are having on them in the most compassionate and curious way possible. As always, my email is a client show at NYTimes.com.

Interview with Julia Ballouz

3:06Julia Blues, welcome to the show. Thank you so much. It's a pleasure to be here. So I was shocked by this number. According to the Kaiser Family Foundation's poll, one in eight Americans are currently taking a GLP-1. Why? Yes, it was surprising to me, too. So one of the ways we can understand this is there's this very long history of people seeking out basically the magical elixir for weight loss, right? So I think that's one piece of it, and now we finally have something

3:37that rivals the only other effective medical intervention we've had to help people lose weight, which is bariatric surgery. On the other hand, there's a lot of people who are living with diabetes, and I think that's another reason that we see so many people who are on these drugs. In addition, I think these drugs have really met a particular moment, which is this algorithmic social media age. They're everywhere in the U.S. We already had this relatively unrestricted approach to marketing pharmaceuticals. We see them advertised everywhere.

4:07We've seen this telemedicine industry flourish since COVID, but also around these drugs. And I think that's why we're seeing these shocking numbers. So I want to start on the part of this that people actually don't talk about that much, which is diabetes, which is what these drugs are originally approved for. As you say, a huge number of Americans have diabetes and have terrible health consequences often from it, including limb amputation and blindness. What do these drugs do for diabetics? Yeah, so our bodies produce GLP-1 naturally.

4:40So we have this hormone that's produced in our gut, in our brains, and to a lesser extent in the pancreas. Basically, they're this synthetic version of a hormone we produce naturally. And the big breakthrough for diabetes was that they're stimulating the pancreas to release insulin only in the context of high blood sugar. So it's not like when you take insulin and you need to be careful about what you're eating and you're at risk of really low blood sugar levels and the dangers that come with that. These are only stimulating insulin secretion when your blood sugar is running high. So as researchers who are working on this

5:11are trying higher and higher doses to help people with diabetes get more and more benefit, they start to discover these weight loss results in the trial. So people start to spontaneously lose weight. And then later, we're finding all these slew of other benefits that no one would have predicted. No pharma company would have bet on this. We're only at the beginning of what's been called this Ozempic era. I think we're really just at the beginning of discovering the benefits and the harms of these drugs. Okay, so you have the recognition,

5:42which is just something people begin observing, that diabetics on these drugs begin to lose weight and they don't feel hungry. And as researchers begin testing, you know, the first generation of this, Ozempic, what we now in that context call Wagovi. How big is the effect size? What do we actually know about what Wagovi does for weight loss? There's another one, which is slightly more advanced. It has more mechanisms of action to his hepatite,

6:12which is also, it goes by Zepbound. How much weight do people lose on these? So it depends on the drug, but we're talking like 15 to 30%. So it's the first time we have a drug that really rivals the more effective types of bariatric surgery. The key point is that it's turning down appetite. So it's not ramping up metabolism or energy burn. And the idea was that this is a gut hormone. That's the thing that a lot of people focused on. It's released after eating and it helps people signal satiety. It helps them feel full

6:42and know that they've eaten. And we're just giving a really souped up version of this gut hormone. And it turns out that actually you need to stimulate the brain GLP-1 system to get the weight loss effects. So you only interfere with appetite once you reach this brain GLP-1 system. You've written or co-written a whole book about the metabolism. And one of the arguments of that book, one of the arguments of books in this space that I think people don't appreciate is that hunger is a function of the brain.

7:13And it's a function of the brain's reaction and predictions about the world around it. We always have this idea that people just feel hungry and then, you know, you should use your brain to decide if you want to eat. But your brain is deciding if you feel hungry and you're sort of fighting its own instincts.

Hunger and Brain Function

7:30So I'd like you to spend a minute on this idea that hunger is a function of the stomach versus hunger is a function of the brain and sort of how research has moved from one to the other. Yeah, the way we describe it in the book, we use this analogy of breathing. So if I tell you, like, take control of your breath right now, like, breathe more slowly or breathe more quickly or hold your breath, you can take control for short periods of time, but eventually physiology takes over. And the same thing is true of what we eat. So we have this illusion of control

8:01over our individual meals and snacks, but there's this symphony of internal signals that's going on inside of us all the time, and the brain is sort of leading this symphony. And the decisions we make are much less a product of conscious control that I think many people appreciate. So when you're taking a GLP-1, you're getting a much higher, longer-lasting version of what your body produces, and it has to reach the brain through the gut-brain barrier. So it has to reach through the gut-brain barrier. And the theory is that

8:32it's reaching into the part of the brain that usually signals that there's a toxin in circulation, and so that shuts down your appetite and increases your nausea. Like what you would get during food poisoning or something? Exactly. Or what you would have on a GLP-1. These are the most common side effects of these drugs, right? So it reaches into that. So the wonder drug we've invented is we've made your brain slightly think it's being poisoned all the time? I think that's one way to put it, absolutely. And so this... Modernity, baby! I know, and in the context of our completely toxic food environment, right?

9:03It's just turning down your appetite by reaching into this GLP-1 brain system. So it reaches through the gut-brain barrier, but it acts as a neurotransmitter in the brain, and from there it reaches other parts of the brain. This is a very active area of research, but that's the sort of bottom line, and this dialing down of appetite is the key feature of these drugs. One of the things that I find interesting about the GLP-1s is we basically created this food environment that does not exist

9:33in nature. of hyper-sugary, hyper-fatty, hyper-salty, hyper-calorie-dense foods. Our brains are evolved over very, very long periods of time to treat those as getting, you know, three cherries on the salt machine and to really, really want them. So we've put people into this hyper-stimulating environment, but we didn't change everybody's brain to turn down the level of hunger when you come into something that is

10:04very calorie-dense or very sugar-dense. And so we've been asking people with these like caveman, all of us, myself, caveman brains now surrounded by the fruits of modern industrialized food production where the Mars company is spending God knows how much on R&D to make my kids want M&Ms. And it doesn't work for people. And then we blame them and tell them they've not done a good job exercising their willpower and self-control. I think you were also someone who struggled with weight earlier in your life. I was very,

10:35very heavy until I was almost an adult. Like I lost like 60-ish pounds, 50-ish pounds when I was 16. And then ever since, like I fight my food desires. Like if we had a bowl of Oreos on this table, 30, 50% of my mental energy the whole time we were talking would be to not eat the Oreos. Right. Yeah, absolutely. I remember we had lunch in Washington when I was doing lots of obesity reporting and you said why am I a person who if the chocolate cake is there like 50% of my brain

11:06is focused on the chocolate cake and I didn't have a good answer for you then. Do you have one now? I do, yeah. I think it's that you know, so when we think about something like common obesity so there's many different types of obesity but what most people have is called common obesity and it arises from these tiny like over a thousand genetic variants that all act almost all act in the brain and so you have a neurobiology probably that's different from someone who doesn't have to fight the chocolate cake and I actually did genetic testing

11:36for the book and I'm also someone who struggles with my weight turns out I have a higher genetic risk than like 90% of the population but this risk in a particular environment won't be expressed but as you said when you put people like us in environments where there's lots of M&M's and lots of chocolate cake it becomes much harder and I think most people don't have this privilege let's say of being able to finally curate their environment to control their weight and maybe the way we might have had I have a family member who I'm not related

12:07to by blood and one thing that always amazes me is she will order dessert and she loves dessert and she loves chocolate cake and she'll like eat half the cake and then take the rest home and I always look at that and I think whatever is happening in you is not happening in me or possibly vice versa whatever is happening in me is not happening in you and then I feel in other ways elsewhere in my life I can have a cigarette or a puff on

12:39a vape I have no interest in another it does not excite any desire in me I can have a whiskey and leave half of it or a glass of wine and I don't particularly want to keep going and I've had people in my life who struggle with alcoholism and I don't have willpower they don't something is happening in their bodies or in their minds that is not happening in mine and I've always thought the way we blame people for this is so cruel because it is so often people who don't have the

13:10propulsive desire blaming people who do for not exercising willpower but those people aren't exercising willpower I'm not exercising willpower to not have more cigarettes I don't want them I know absolutely I have this conversation all the time with my husband for some people the cards are just stacked against them one person that really helped my thinking on this was Robert Sapolsky who you've probably talked to yeah yeah he talks about how we have these potentials or vulnerabilities that are created by our genetics

13:41and then in different environments they're either expressed or activated or not not expressed right like it's extremely hard to you know do the right thing to buy the foods that you know you should be eating or to exercise every day when you're working the night shift and you're raising kids and you're this single mom or dad or whatever it is like how are you going to do all the things that you know you need to be doing to protect your health and to fight against this neurobiology that you might have so you have this interplay of biology neurobiology as you're

14:12as you're saying it this thing we call willpower which is a very poorly specified concept and then environment to me this question of environment is really important I'll use myself as the example you know when I lost a lot of weight I mean when I was younger a lot younger I was a high school student with nothing to do and I was able to really really hold that when I was a young adult and I have not been able to diet successfully since I had kids

14:42because I can't control the food environment and there's a lot of other things I can control I can go to the gym I have a certain amount of autonomy over my schedule so as you say when you add in things like the night shift when you add in not having the money to get healthy foods or go to the gym when you add in having more kids or less time willpower works very very differently when you're able to have the autonomy or the money to create a certain kind of environment around you that is conducive

15:13to living in a certain way right you're a Hollywood celebrity with a personal chef versus you're a single mother of four who works two jobs and this idea that like willpower is some unchanging muscle inside the mind as opposed to some reserve discipline that gets depleted like if I don't sleep enough I eat more right absolutely and you're designed to eat more when you don't sleep enough and you're absolutely right that this symphony of internal signals that I was referring to earlier it's interplaying with our environment

15:44so one thing I've really appreciated about your work on the GLP ones as a reporter and as somebody who's very deep in the science is you've done a tremendous amount of interviewing people on them and you've interviewed many of the kinds of people and again to me this has always been the cruelty of this conversation who were exercising a tremendous amount of constant willpower going on and off like very restrictive diets you know losing 30 pounds gaining it back what is it like for them for the people who've seen huge amounts of weight loss

16:15how do they describe the experience of being on a GLP-1 versus what it's like off of one I think the big common thread for people in whom the drugs are effective for weight loss is this idea that suddenly this willpower that they were always searching for that they feel they didn't have enough of suddenly they have it suddenly it's not that hard to say no to the extra piece of cake or the cake all together they're eating smaller portions their cravings change like there's a lot of discussion about food

16:46noise so that's this when the cake is there 30 to 50 percent of your brain is on the cake or you have cravings that distract you a lot of people say that this just disappears you said a second ago for whom the drugs are effective for whom are they effective and for whom aren't they effective and why so this is another area we don't fully understand but it seems like there are some people who are quite sensitive to the drugs and others who are insensitive to the drugs and there might be a genetic component to this too that

17:16that's sort of a frontier area of science and so I think the quest that a lot of the companies are on is to understand like how do we differentiate the people who might need higher doses initially or much lower doses because they're having so much sensitivity to the drugs and side effects and whatnot they're having such a strong response or losing weight too fast so there absolutely is this variation in how people are responding tell me about the side effects of these GLP-1 drugs in studies

17:47people often don't stay on them that long people do cycle off of them sometimes for cost but sometimes for other reasons like what is unpleasant on them what can go wrong so the most common that we know of right now are the gastrointestinal side effects so the nausea the vomiting the diarrhea those are the most common but it seems like there's other emerging potential problems so there are lawsuits around severe stomach problems damage to the ocular nerve so eye damage and those I don't think we have clear answers on how

18:17common that is but the basis of those lawsuits is that people weren't properly warned that this could happen one thing that a lot of people don't seem to be warned about is the fact that you have to stay on them to keep reaping the weight loss benefits there's an idea that a lot of people have I'll lose the weight I'll learn how to eat properly and then I'll go off the drugs I'm always surprised that even people who got the drugs from their doctors don't seem to what happens when people go off the drugs you tend to regain the weight and it's not you just feel hungrier again the appetite

18:48resets exactly this appetite that was suppressed through acting on the brain GLP-1 brain system that effect is gone and you're back to the food noise you're back to the hunger that you had before I've heard this and it's definitely true in the data but I guess people in my life have chronic conditions and the drugs are on they just have to stay on them you stop taking statins and the effect goes away if you're a diabetic you have to keep taking insulin I feel like that's like people who are used to drugs to treat

19:18acute conditions not being used to drugs to treat chronic conditions but I think this is the thing that goes back to the beginning of the conversation that a lot of people still have this idea that they should just be able to will their way out of it right I think these drugs helped reveal how much we are products of our physiology and that with this you know you take this drug and suddenly again you have the willpower you didn't have for your whole life but there's still this expectation it's like any other diet and that feels like a place where people

19:49haven't been warned but as we've been saying there are now so many people on the drugs and I think these more rare side effects we're going to start to learn

Social and Cultural Implications

19:56more about I want to talk about a possible social side effect which is our culture's expectations for what people's bodies should look like have been punishing for a long time particularly punishing for women and girls I think we've interestingly been entering an era where they're increasingly punishing on boys and men and there's this whole thing of male looks maxing and the guys in the Marvel movies are completely jacked now and on all kinds of things you probably shouldn't be taking and

20:28you know if you're obese or overweight and you're taking a GLP-1 to lose weight or to protect your cardiovascular system you know great but I think a lot of the cultural effect of them has come from celebrities and influencers who all of a sudden show up and are much thinner at times skeletal now in ways that when you have the body's natural hunger signals coming back at you is harder to do

20:59you know there was like this big body positivity movement and that was always going to be a very uphill climb in this country but how do you think about GLP-1s as possibly a pharmaceutical accelerator of you know fairly dangerous body expectations because now it's like well if you want to look thinner why not just go on a GLP-1 that's absolutely a strand in this conversation and in this moment that we're living in the place that it

21:29freaks me out the most is I talk to pediatricians who are prescribing the drugs in children there's no screening yet for these drugs and eating disorders in young people and they anecdotally have seen people use these as aids for essentially eating disorders and kind of exacerbating eating disordered behavior one of the underlying assumptions of the health at every size or fat activism or body positivity movements was that you can't control your body size therefore you must accept it we had

21:59surgery before it wasn't as accessible or scalable but now we do have this medication where people do have the option right or at least the ones who are sensitive to it and the ones and access it and all of that we've seen influential people in the body positivity fat activism movement come forward and really grapple with starting on these drugs and losing weight on them and one thing that those movements did that was really important was highlight how much shame and stigma people who are living with obesity face every day especially

22:30women so like there was this great economist article a few years ago where they parsed the data on the pay penalty and they did such a great job of highlighting the discrimination and stigma that people with obesity face but I think there was really a dangerous glossing over of the health effects of carrying extra weight that even if there is this variation in individuals at the population level it's very clear that the higher you go up the BMI ladder the more health risks you're carrying

23:01I've spoken I've spoken to people who are part of these movements they had issues with movement they had problems with their blood sugar they were concerned about fertility and they were so grateful to be able to now have a medication that could help with those issues that debate became very polarized it was either you're fat accepting or fat phobic and I think we're kind

23:43and you know one thing that the people I know are worried about and frankly that I'm worried about I mean I feel like I would not have had this concern for like young boys which is what I have a while ago and now I look at the rise of male looks maxers and it looks a lot like toxic diet culture that girls were exposed to before you know and obviously clavicular who is the avatar of that has talked a lot about being on you know GLP-1s or some form of these drugs I wonder

24:13going to do when it is just that much easier for people at the top of society to exert heretofore unknown levels of control over their bodies and when they're doing it with these like wild stacks of GLP-1s and peptides and you know pills to prevent hair loss and everything else you know constant Botox