Ozempic: Miracle Weight Loss Drug Or A Secret Killer? - Johann Hari

1. 0:00 – 5:11

   Johann’s Weight Loss

   1. CWChris Williamson0:00

      Johann Hari, welcome to the show.

   2. JHJohann Hari0:01

      Hey, Chris. Great to be with you again.

   3. CWChris Williamson0:03

      How are you? You've lost a lot of weight.

   4. JHJohann Hari0:06

      I have. I've lost, what I believe the technical term is a shitload of weight. I've lost three stone. I'm good. I'm cheerful. Life is good. Can't complain.

   5. CWChris Williamson0:14

      Talk to me about where this weight loss has come from.

   6. JHJohann Hari0:18

      Well, I remember the exact moment it all began. It was the winter of 2022, and I got invited to a party, and it was that moment, I hadn't been to a party in whatever it was, a year and a half, two years, 'cause the world was shut down. And I thought, "Fuck it, I'm gonna go to this party." And I was in the Uber on the way there, and I felt a little bit self-conscious 'cause I'd gained a load of weight, and I was quite fat at the start, and I'd gained a load of weight. And the party was being thrown by an Oscar-winning actor. I'm not saying that just to name drop. It's relevant to what happened next. And on the way there, I was both feeling this kind of like, ugh, bit schlubby and embarrassed, but I also thought, "Oh, wait, everyone I know gained weight during lockdown. This is gonna be fascinating. It's gonna be super interesting to see these Hollywood people with a bit of podge on them." And I arrived, and it was the weirdest sensation. It's not just that they hadn't gained weight. Everyone was gaunt, right? Everyone had lost, visibly lost weight. They looked like their own Snapchat filters. Do you know what I mean? They were, like, sharper and clearer. And I was stumbling around in a bit of a daze, and I bumped into an old friend of mine on the dance floor, and I, I said to her, "Shit, looks like everyone really did take up Pilates during lockdown, huh?" And she laughed at me, and I- I didn't know why she was laughing. I must have done a kind of strange face! And she said, "Well, Johann, you know it wasn't Pilates, right?" And she pulled up on her phone an image of an Ozempic pen. So, I did not know at that point that we now have a new kind of weight loss drug that works in a totally new way that causes people to lose 15% of their body weight. For the next version of this class of drug, Mounjaro, you lose 21% of your body weight, and for the next one, triple G, that will probably come online next year, people lose 24% of their body weight. And when I started to learn about this, I don't remember any subject in my whole life, actually, where I immediately felt so divided about it. So, I could obviously see the importance of it straight away, right? I knew even then that obesity is really bad for your health. You know, it makes over 200 diseases and complications more likely. And this wasn't an abstract question for me. I'm older than my grandfather ever got to be, 'cause he died of a heart attack when he was 44. My dad had very bad heart problems. My uncle died of a heart attack. Men on both sides of my family. So I thought, "Okay, if there's a drug that reverses or massively reduces obesity, that's a big deal." I also thought, "Come on now. Can you really have such a thing as a free lunch?" I guess with Ozempic it'd be a smaller free lunch. I thought, "I've seen this story before, right?" Every 20 years or so, going right back to the First World War, a new miracle diet drug is announced, and people stampede to get it. They take it in huge numbers, and we always discover it causes some horrendous dark side effect, and it has to be yanked from the market, leaving a trail of, you know, devastated people in its wake. And I was worried about lots of things. So, really, to get to the bottom of this, for a year I took the drug, and I went on a big journey all over the world, from Iceland to Minneapolis to Tokyo, to interview huge array of people on this, the biggest defenders of the drugs, including the people who made the breakthroughs that made it possible, the biggest critics of the drugs, everyone in between. And it's a weird thing that I'm sure will come out in our conversation, Chris. I learned a huge amount about the extraordinary benefits and the 12 disturbing risks of these drugs. Um, I learned that, about the incredible effects it's gonna have on the culture, including the people who don't even wanna take these drugs. But I'm s- gotta admit, I'm still pretty conflicted. It's actually a pretty complicated picture, where people are gonna have to weigh for themselves the, the benefits and the risks.

   7. CWChris Williamson3:54

      And are you still on it now?

   8. JHJohann Hari3:55

      I decided to carry on taking it. After going, after looking very closely at the benefits and risks, for me, the benefit that was just overriding is if you take these drugs and you had a BMI of 27 or higher when you start, it reduces your risk of a heart attack or stroke by 20%. So, although I am very worried about some of the risks, including for myself, and I'm very worried for a lot of people I know taking them for various reasons, for me, that benefit just outweighed the risk. And for me-

   9. CWChris Williamson4:24

      So, it's, uh, a cost-benefit analysis?

   10. JHJohann Hari4:25

       Absolutely. All the way through this, we've got to be doing cost-benefit analyses between two things, really. The risk of continuing to be obese, which for me, realistically, is what would have been the case, right? I had tried dieting and exercise loads of times. I'd lost weight, and it had always come back. Versus the risks of these drugs. That won't be the choice for everyone. Clearly, if you can lose weight without these drugs, you should. It's obviously better, and some, there's a minority of people who can. Um, and all credit to them. But for the people who can't, that's basically the choice we face. Now, we can make big changes as a culture so our kids don't face these choices. And I went to places like Japan that have made those changes, where, you know, there are almost no obese people, and they don't have, they're not in this fucking shitty trap. But for the rest of us, that's the choice we've got at the moment.

2. 5:11 – 11:29

   Is This Any Different to Previous Pills?

   1. JHJohann Hari5:11

   2. CWChris Williamson5:11

      You mentioned the fact that every 20 years or so, there is a new miracle anti-obesity weight loss drug that gets released. Just how different is the GLP-1 agonists to what we've seen before?

   3. JHJohann Hari5:25

      Well, it works in a totally different way, but I think it's worth just giving an example of one of those previous drugs. There's a lot of them. But let's think about one in the mid-'90s called Fen-phen that was talked about in exactly the way Ozempic is talked about now, right? Literally the front page of Time magazine was the new miracle weight loss drug. So, by 1995, 18 million prescriptions were written in the United States alone for this drug. And it was a combination of two things. It was an appetite suppressant called flexfluramine, which had been around for a long time, but made you very drowsy, so was never that popular, with an amphetamine called phentermine, which had the advantage that it made you, woke you up, and also caused a bit more weight loss. And this drug was hugely popular and massively widely used. And then it was discovered...It caused a series of horrific problems. It caused a horrific lung disease problem and caused heart defects. Had to be yanked from the market. It led to the biggest compensation payout in the history of the pharmaceutical industry at that point, $12 billion. So obviously, you come at this... And all the previous diet drugs have that trajectory, right? So you come at this with a lot of anxiety, rational anxiety, right? So these drugs work in a completely different way to all previous weight-loss drugs. And it's- and there's a- one of the things that's weird about it is there's actually a big debate about what these drugs even do, which is a bit disconcerting. But here's what we know for sure. If you ate something now, Chris, doesn't matter what it is, after a while, your pancreas would produce a hormone called GLP-1. And GLP-1, we now know, is just part of your body's natural systems going, "Hey, Chris, you've had enough. Stop eating now," right? But that natural GLP-1 only stays in your system for a few minutes, and then it's washed away. And then obviously, you can just carry on pigging out if you want to. What these drugs do is they inject you with an artificial copy of GLP-1, that instead of sticking around just for a few minutes, sticks around for a whole week. So it has this weird effect. I'll never forget, the second day after I injected myself with Ozempic, I woke up, I was lying in bed, and I thought, "Oh, I feel something really weird. What is it that I'm feeling?" And I couldn't place it. I felt nauseous, but I knew it'd feel that. Ev- almost everyone feels nauseous. It wasn't that bad. So something else that... And it took me a while to realize, "Shit, I've woken up and I'm not hungry," right? Every day before that, going back to being a kid, I used to be woken up with like a raging hunger, right? And I went to, there's a cafe just up the road from where I live, and I ordered the thing I used to get for breakfast every day, a massive brown roll with a shitload of chicken and a shitload of mayo in it. And I had like three or four mouthfuls, and I just felt full. I couldn't eat anymore. It was almost like how you'd feel after like Christmas or Thanksgiving dinner. You know, imagine you'd eaten the whole dinner, you were stuffed, then I turned up and said, "Hey, Chris, mate, I've got you a KFC bucket," right? You'd just be like, "No way." I felt like that after about three or four mouthfuls. Um, and then for lunch, again, I went to this Turkish restaurant next to my office I used to go to every day. I ordered a big Mediterranean lamb, which is what I used to always order. Again, like three or four mouthfuls, I felt full. So what we know is the drug makes you feel full very quickly, very fast. It was initially thought because that's a hormone that's made in your gut, the effect is probably primarily in your gut, that it slows down gastric emptying, for example. We now know there is definitely an effect on your gut, but we now know that there are GLP-1 receptors not just in your gut, but in your brain. And from interviewing the cutting-edge neuroscientists and really looking deeply into their work, it's increasingly clear that these drugs are not actually primarily working on your gut. They're primarily working on your brain. They're changing what you want. Um, there's a huge debate about what that specific change is, what it means, the additional benefits and risks that might flow from the fact that this is a brain-changing drug. But those are things we know for sure. There's a huge amount we, we don't know and a huge amount of detail, obviously, in everything I just said.

   4. CWChris Williamson9:22

      What is it like mentally, physically, energetically, psychologically to take these drugs? How does it feel?

   5. JHJohann Hari9:30

      Different people have different effects. So there's a few effects that most people get. So almost everyone gets nauseous at first. You start off on a s- low dose. Um, it's partly because what these drugs do is they produce a feeling of satiety, the feeling of being full. And the human body isn't very good at distinguishing between satiety and nausea. That's why often if you, you know, when you're really full, you actually feel a little bit sick, even just without these drugs. So you feel nauseous, you start on a low dose, gets you used to it. For about 5% of people in the clinical trials, the nausea was just so horrific, they stopped taking the drug. And I interviewed some people who had really terrible experiences with the nausea. For me, I think I was pretty normal. It was unpleasant, but if on a random day, like three years ago, I had felt that nauseous, I wouldn't have like stopped going about my day. Do you know what I mean? It wasn't so bad that it would have made me go to bed or anything. It was just not nice. Um, you feel nauseous. A lot of people get constipated. Um, various other side effects. For me, actually, I didn't- those side effects didn't bother me that much, although I got them a bit. Actually, weirdly, I got a side effect that's a more minority side effect, but is in the warnings. It's not uncommon. It makes your heart race a bit faster, fair bit faster for a minority of people, which is hard to not- it's hard to not feel a little bit anxious if your heart is racing. You're a bit like, "Shit, what's wrong? What's going on?" Then you go, "Oh no, it's just a side effect," right? Although, as Professor Carell LaRue, one of the scientists who developed these drugs, said to me, "There's two kinds of drugs in the world. There's drugs that don't work, and there's drugs that have side effects, right?"

   6. CWChris Williamson11:03

      Ah.

   7. JHJohann Hari11:04

      (laughs) So the initial, the initial side effects, those are the kind of normal feelings, but the main sensation is a bizarre feeling of satiety, of feeling full, of feeling really full really fast. And that doesn't go away, right? It's why you eat dramatically less, and it's why, you know, you lose, on average, a shitload of weight, to use the clinical language.

3. 11:29 – 15:10

   How Common Are Weight Loss Drugs?

   1. JHJohann Hari11:29

   2. CWChris Williamson11:29

      How common is this? How many people are taking it, and famous people, and all the rest of it?

   3. JHJohann Hari11:35

      It's absolutely massive. 47% of Americans in a recent poll said they want to take these drugs. It's really worth pausing and thinking about. A lot of my book is exploring how the fuck did we get to this point where almost half the population feel they need to drug themselves to eat less, right? That's an extraordinary moment in human history. We actually know why it happened. So there's far more people want to take these drugs than can possibly take them, partly because every person who takes them then becomes a walking advertisement for the drug. I think, for example, about a guy I interviewed called Jeff Parker. He's a 67-year-old former lighting engineer in San Francisco. Super nice guy. And he was very severely overweight.He was a pretty bad way, he had gout, he had kidney problems, liver problems. He was finding it quite painful to walk. Every morning, he had to swallow fistfuls of pills from the doctor. He started to take Mounjaro, which is one of these drugs, and very rapidly lost a huge amount of weight. His doctor took him off almost all his pills. Now, every day, he walks his dog over the Golden Gate Bridge, he told me, "I feel like I'm gonna enjoy my retirement now." Now, everyone who knows Jeff, when they see him goes, "Shit, what happened to Jeff? What's going on there?" And he goes, "Oh, I'm taking Mounjaro, right?" So partly what's happening, the reason why there keep being these chronic shortages of the drugs, is that the drug companies are racing to meet a finish line that keeps getting further and further away.

   4. CWChris Williamson12:57

      Mm.

   5. JHJohann Hari12:57

      Because everyone who uses it inspires another five people to wanna use it, and then they demand it, and it's going up and up and up. So this is massive. If you wanna know how huge it's gonna be, um, we're talking obviously a lot here about the benefits quite rightly, I'm also quite worried about the rest. But if you wanna, wanna know how influential this is gonna be, I actually think the best people to look at are the financial analysts who've been looking at this. So Barclays Bank commissioned a very sober-minded financial analyst called Emily Field to go away and investigate these drugs, figure out what's going on, to guide their future investment decisions, right? Because obviously they're making huge investment decisions the whole time. She came back and said, "If you want a comparison for the effect these drugs will have, you've got to look at the invention of the smartphone." Right? So look at this, this is me talking now, not her. Look at so many of the effects this is already having on the economy. Krispy Kreme doughnuts, their stocks have gone down. Nestle, the CEO Mark Schneider, making a lot of worrying noises about ice cream. Jefferies Financial just did a big report for the US airlines saying they're gonna have to spend a lot less money on jet fuel pretty soon, 'cause it takes a lot less jet fuel to fly a much thinner population. There's a company that makes hinges for knee and hip replacements. Their stocks have tanked, because the main driver of knee and hip replacements is obesity, and there's gonna be a lot fewer obese people, right? If you think about jewelers in LA, jewelers have had a huge run, 'cause people's fingers are shrinking so much on those end You're kidding me. People have had to have their-

   6. CWChris Williamson14:23

      You're kidding me.

   7. JHJohann Hari14:23

      ... wedding rings refitted, right?

   8. CWChris Williamson14:25

      Wow.

   9. JHJohann Hari14:26

      Wild situation. So if we had been talking in whatever it was, I think it was April 2007 when Steve Jobs first unveiled the iPhone, you and me would not have been able to game out, you know, TikTok and Uber Eats and Hinge and all these other things that have transformed our lives, right, as the result of that moment. But I think we can begin to see some of the ways... I mean, we're gonna have a situation, especially since 10 years from now, these drugs will almost certainly be a daily pill that costs about a dollar a day. I- my anticipation is if we don't discover some horrific side effect, and we might well-

   10. CWChris Williamson14:59

       Mm.

   11. JHJohann Hari14:59

       ... but if we don't, I would anticipate half the population of the United States will be taking these drugs and it will have incalculably huge consequences for the way we all live.

   12. CWChris Williamson15:09

       Why

4. 15:10 – 21:29

   Why Society Has Become More Obese

   1. CWChris Williamson15:10

      has society become so much heavier then?

   2. JHJohann Hari15:14

      It's crazy to think about this. I was actually stunned when I looked at the evidence on it, right? You're younger than me, aren't you, Chris? How old are you?

   3. CWChris Williamson15:21

      36.

   4. JHJohann Hari15:22

      Right, so you're a little bit younger than me, I'm 45. I'm gonna pretend that's a little bit younger. Um, so look at a photo from just before we were born, right? I'd urge people to Google, if you're in the US, google, uh, "photos of Americans on the beach 1975." Right? Or for Britain or Australia, whatever country you're in. When you first look at it, it- it seems really strange to us, when you look at these photos, 'cause everyone is what we would call skinny, right? Everyone. And you're like, "Well, where was everyone else on the beach that day? What's going on? Was it a skinny person convention on the beach? What's happening?" And then you look at the figures, that is what people look like in 1975, right? So between, I was born in 1979. Between the year I was born and the year I turned 21, obesity doubled in the United States, and then in the next 20 years, obesity, severe obesity, more than doubled again, right? Britain, the country we're from, very similar. Year I was born, 6% of British people were obese. Uh, by the time I was, you know, 45 now, it's 27% of British people. And it's important to understand, you've got 300,000 years where human beings exist and obesity is exceptionally rare. And then literally in my lifetime, this unprecedented explosion. The World Health Organization says obesity has more than trebled in the world, right? In my lifetime. Obviously I'm not blaming myself, I'm not like some antichrist figure that caused it. So what's happening here, right? I looked at the science, and it's actually on this, pretty straightforward. Obesity explodes in every single country that makes one change and one change only. It's where people move from mostly eating fresh, whole foods that they prepare on the day they consume, to mostly eating processed and ultra-processed foods that are constructed out of chemicals in factories in a process that isn't even called cooking, it's called manufacturing food. And it turns out this new kind of food which our grandparents wouldn't even have recognized, and no humans before have ever eaten, affects our bodies in a profoundly different way. And it actually comes back to the word that we've been associating with these drugs, really importantly, satiety. These drugs undermine your, sorry, this food undermines your satiety, it undermines your ability to feel full and to know when to stop eating. And there was an experiment, and there's loads of evidence for this that go through the seven reasons why this food undermines our satiety, but there's an experiment that, to me, just totally distilled it. There's a professor, a brilliant professor called Paul Kenny, he should have me on a podcast, this brilliant person, who's the head of neuroscience at Mount Sinai in New York. And he grew up in Dublin in Ireland. And in the '90s he moved to San Diego to continue his scientific research, and he quickly clocked Americans don't eat like British people, right? Sorry. Oh fuck, don't wanna offend the Irish if I say that.

   5. CWChris Williamson18:08

      Ha.

   6. JHJohann Hari18:09

      And he qui- (laughs) he quickly clocked, he quickly clocked that Americans don't eat like Irish people did at the time, right? They ate much more processed and ultra-processed food, they ate much more sugary, salty food. And like many a good immigrant, he quickly assimilated, I see you haven't done this, Chris, and within a year he gained 30 pounds. And he started to feel like this food he was eating-... wasn't just changing his gut, it was changing his mind, right? It was making him want different things. So he did an experiment to test this, which I have nicknamed Cheesecake Park. It's very simple. He raised a load of rats in a cage and they had nothing to eat, but the kinda healthy whole foods that rats evolve to eat over thousands of years, right? They got it in pellet form, but it's the food they're used to, right? And when they've got that food, the rats eat when they're hungry and they stop. They never make themselves fat. When they've got the kind of food they evolved for, they have some kind of natural nutritional wisdom that kicks in and says, "All right, mate, enough," right? Then Professor Kenny introduced these rats to the American diet. He fried up a load of bacon. He bought a load of Snickers bars, and crucially, he got a load of cheesecake and he put it into the cage, and they still had the healthy food if they wanted it. The rats went ape shit for the American diet. They would hurl themselves into the cheesecake and literally eat their way out, emerging just totally fucking smothered with cheesecake, right? Um, and all this nutritional wisdom they'd had when they had the kind of food they evolved for disappeared. The way Professor Kenny put it to me was within a couple of days, they were different animals, right? They ate and ate and ate and ate, and very rapidly, they were all obese. Then Professor Kenny tweaked the experiment again in a way that, as a former junk food addict, seems pretty cruel to me. He took away the American diet, and he left them with nothing but the healthy food, and he was pretty sure he knew what would happen. They would eat more of the healthy food than they had before, and this would prove that the kind of American diet expands the number of calories you eat every day. That is not what happened. Something much fucking weirder happened. Once they'd been exposed to the American diet and it was taken away, they refused to eat the healthy food at all. It was like they no longer recognized it as food. It was only when they were literally starving that they went back to properly eating it, right? Now, this fits with a much wider body of evidence in human beings. As Gerald Mand, Professor Gerald Mand, who's at Harvard, uh, who designed the food label that's on all food that's sold in the US, as he put it to me, there's something about the food we're eating that is undermining our ability to know when to stop, right? And for a long time, I was investigating that question, right? "Uh, why have we gained so much weight?" And I was also investigating how do these drugs work, right? And I thought they were different topics that would meet up at the end because obviously we got fat and that's why we want the drugs. But actually, it's much more densely interconnected than that. The- this processed food undermines our satiety, and what these drugs do is they give you back your satiety, right? In fact, one of the scientists says what they give you is satiety hormones. But when you see it that way, suddenly you realize, as Professor Michael Lowe put it to me, these drugs are an artificial solution for an artificial problem, right? Processed food digs the hole of hunger that I've had inside me my whole fucking life, and these drugs fill that hole in, but come with their own set of risks.

   7. CWChris Williamson21:28

      Yeah,

5. 21:29 – 30:19

   Taking Away the Pleasure of Good Food

   1. CWChris Williamson21:29

      so these drugs are rebalancing the scales of a novel food environment that we've only recently created.

   2. JHJohann Hari21:36

      That's a brilliant way of putting it. Exactly right.

   3. CWChris Williamson21:37

      But it's adding more tension to the system, right? It's not like it precisely re- well, it, it does rebalance the scales, but it rebalances the scales by adding weight on both sides. You're now still probably eating the same hyper-palatable stuff, just less of it, and you're having to take the drug to improve your society-level satiety so that you don't have the problem.

   4. JHJohann Hari21:57

      Yeah, it's a good way of putting it. I mean, some people do more radically change their diet. I actually was eating smaller portions of the same old shit for a long time, and I have now changed a bit. I wouldn't wanna overstate it, but-

   5. CWChris Williamson22:05

      I- does it want you- does it make you want to eat different sorts of foods? Does it make hyper-palatable foods less palatable?

   6. JHJohann Hari22:12

      S- yes, but interestingly, there's a range of experiences in this. So I was unusual. So I just wanna preface this by saying my diet was unbelievably shit before this, right? One of the lowest points of my life was... I could tell you exactly when it happened. Christmas Eve 2009 at 1:00 PM, I went into my local branch of KFC in east- the east end of London where I used to live. And I went in, I said, my standard order, which is so disgusting I'm not gonna say it in front of someone who looks as glowingly healthy as you, Chris. And the guy behind the counter said, "Oh, Johann, I'm really glad you're here." I was like, "All right." And he went off beh- behind where they fry all the chicken and everything. And he came back with all the other people who were working that day and a fucking massive Christmas card in which they'd written, "To our best customer," and everyone had written like personal messages for me. And one of the reasons my heart sank is I thought, "This isn't even the fried chicken shop I come to the most," right? (laughs)

   7. CWChris Williamson23:05

      Wow.

   8. JHJohann Hari23:05

      How could this be fucking happening to me? It was a bad day, right? It was the second-worst moment in the- my life of being fat. The worst was when I was fat-shamed by the Dalai Lama, but that's a different story.

   9. CWChris Williamson23:14

      (laughs)

   10. JHJohann Hari23:14

       Turns out he's a total fucking bitch, but who knew?

   11. CWChris Williamson23:16

       Ah. (laughs)

   12. JHJohann Hari23:18

       Um, but the- but the- so this- this- for me, you know, that was my diet, right? Going right back to when I was a kid. I was raised by my mum and my grandmother who were working class Scottish women whose way of giving love was to give you shitty food, right? And God bless them, they're am- amazing people. Um, and a lot of people, the worst effect of the drug for them is it kills their pleasure in food. So think, for example, about Jay Rayner, who's a brilliant British food critic. I'm sure you've read him. He writes for The Guardian and The Observer. He, um, he started to take Ozempic, and he describes going into like the best Michelin-starred restaurants in Paris, and to him, it was like a lump of wood, right? A lot of people report this problem. He gets-

   13. CWChris Williamson24:03

       Wha- when is- is that a down regulation of the way that your taste buds work? Have you got any idea what the mechanism is?

   14. JHJohann Hari24:08

       No one knows. You ask the experts and they go, "Uh, we don't know." I mean, there's different speculative theories, but we basically don't know.

   15. CWChris Williamson24:14

       Hmm.

   16. JHJohann Hari24:15

       Um, and- and- and this is a big worry. Jens Jules Holst, who was one of the scientists who designed these drugs for Novo Nordisk, said in an interview with Wired magazine, you know, "This is gonna make these drugs unsustainable. People just can't live without the pleasure of food. After a couple of years, people are like, 'This is too boring. I'm gonna give it up.'" Weirdly for me, and I wanna stress, I know I'm an outlier.... It had the opposite effect. But for a slightly weird reason. So I grew up eating shit, right? And I ate huge amounts of shit. And I grew up in, um... We've talked about this before, but I grew up in a family where there was a lot of addiction and mental illness and kind of, uh, craziness. And I realize now, looking back, I never really ate for like much... Very little of my motivation in eating, not nothing, but little of my motivation in eating was actually the pleasure of the flavor and the texture. I was eating to kind of stuff myself, to calm myself down, to manage my emotions. I wasn't... Not totally consciously. Not totally unconsciously either, but, you know. Um, and with these drugs, what happened to me, I remember going out for dinner with a friend of mine, and she said to me, after I'd started taking them, said to me, "You know, it's always been a bit weird eating with you 'cause you eat so fucking much so fast, but you don't really seem to enjoy it very much. Now, you're eating so much more slowly, you do actually look like you're enjoying your food." So for me, I've actually gone from very low pleasure in food to a little bit of pleasure in food, right? So, yeah.

   17. CWChris Williamson25:37

       I think that's- that's something that people don't often think about that many people don't eat food to enjoy the process. They do it to just have that sense of being full in their stomach. It's almost like, you know, topping off your esophagus with a little bit more food in the end, and that's kind of the sensation that they're chasing.

   18. JHJohann Hari25:55

       Totally, and it was fascinating to go through. So in the book I explain, there's actually five reasons why we eat. Only one of them is the one that is the most obvious, which is feeding your body, right? Like, ha- staying alive, the need for sustenance. Actually, and I realize how little of my eating was about that. I mean, I used to eat 3,200 calories a day, now I eat about 1,800. I would have sworn I ate that food to sustain my body, but here I am, you know, better than I was, right?

   19. CWChris Williamson26:19

       Still living, yeah.

   20. JHJohann Hari26:20

       Exactly. Certainly not dead, right? Um, so what else is going on? And one of the really interesting things is one of the fascinating things about these drugs that I was not prepared for is, because they interrupt your eating pattern so radically, you can't carry on eating the way you did before, what they can do, for some people, not everyone, is they bring to the surface the underlying psychological drivers of why you were eating, right? Now, that can be a good thing. It can come to the surface and you can deal with it. But at first, it's quite painful. So I remember very vividly a moment I had an epiphany about this. It was seven months into taking the drugs, and I was in Las Vegas. As you know, I'm writing a book about a series of murders that have been happening in Vegas that I've been researching for a long time. And I was researching the murder of someone that I knew and loved, so, you know, it's pretty unpleasant thing to do. So I had a rough day, and totally on autopilot I went to a KFC I'd been to a thousand times. For people in Vegas, it's the KFC on West Sahara, which I maintain is the grimmest KFC in the whole world. And believe me, I've been to very many of them. But anyway, and I went in and I ordered, um, what I would have ordered a year before, just a bucket of fried chicken, right? And I sat there, and I had a chicken drumstick, and, uh, suddenly I looked at this chicken and thought, "Fuck, I can't eat this. I'm just gonna have to feel bad," right? And Colonel Sanders was on the wall there like he's in all KFCs, and it's like he was looking down at me going, "Hey, buddy, what happened to my best customer?" Right? So it definitely surfaces these strange and unexpected emotions. Now, that can be very dramatic, we know. So one of the best ways of thinking about the- what these drugs do for us, both the benefits and the risks, is actually to look at a parallel area of science, I think. These drugs have only been used for obesity for a couple of years, so we've got a fair bit of evidence, but, you know, we'll know a lot more as the years pass. But actually it's a very good comparison point, I think. Not perfect, but good. It's actually bariatric surgery. So up to now, it's been hard. Certainly not impossible, but it's been hard to lose a huge amount of weight very quickly and keep it off sustainably over the long term, right? The best comparison point is bariatric surgery. Things like stomach stapling, stomach s- gastric sleeves, that kind of thing. So we can look at, well, what happens to people when they have bariatric surgery? Now, some of it is negative. Think about what we just said about comfort eating and the other psychological factors. We know that if you have bariatric surgery, your suicide risk almost quadruples in the years that follow. Quite shocking, right? Now, I think that's- that maybe some of it is that the surgery is actually pretty rough, and you- you have horrible, uh, physical effects afterwards for some people. That'll be a factor for some of them. But I think most of it is, look, by definition if you needed bariatric surgery, you were severely overweight, so you were very heavily eating. A very large number of those people will have been using food to numb or- their emotions, or comfort themselves, or regulate their emotions. And if that's taken away from you, you- you can't do that after bariatric surgery. For a lot of people, that will- that will, at least for a while, manifest as just profound psychological distress. But you also see if you look at bariatric surgery the staggering benefits, right? So it's a really rough operation. One in a thousand people die during the operation, right? It's no joke. But if you survive it, why does anyone do it? It's because the benefits of reversing or reducing obesity for your health are staggering. If you have bariatric surgery, in the seven years that follow, you are 56% less likely to die of a heart attack. You are 60% less likely to die of cancer. You are 92% less likely to die of diabetes-related causes. And you are... It's so good for your health that you're actually 40% less likely to die of anything at all, right? (laughs) That's how good it is for you. So you begin to see, again, that very difficult cost-benefit analysis, right? You get huge benefits to your health from reversing obesity, but there's psychological costs and there are also costs with these drugs, physical risks, and, um, dangers that you don't get with bariatric surgery.

6. 30:19 – 38:05

   Why Not Just Diet & Exercise?

   1. JHJohann Hari30:19

   2. CWChris Williamson30:19

      What about the people who say, "This is all bullshit, can't you just diet and exercise?"

   3. JHJohann Hari30:25

      Yeah. I mean, I kept thinking that to myself the whole way through. I remember few months into taking them, I'm sitting... I was having dinner with my friend Dave, he was eating a massive chicken schnitzel, and I went- talking to him about benefits and risks, right? I'm going, "Oh, there's benefits to drugs, benefits to risks." And Dave said, "What the fuck are you talking about, Johann? There's a third option. I've seen you do it."...go on a fucking diet, right? (laughs) Like exercise. I've seen that when you do that, you lose weight. And, you know, I'd done that many times, and it had worked, right? So I spent a lot of time looking at the science of dieting and what we actually know about it. There's a few things we know for sure. If you understand the laws of physics, you know this is true. If you burn more calories than you consume, you will lose weight, right? No one disputes or no sensible person disputes that, right? So you hear that, and yet you look at the evidence, most people on diets over time do not lose weight. And you're like, "What's going on here?" So I went and interviewed the leading expert on diets in the world, from my point of view, brilliant professor called Tracy Mann who's in Minneapolis. Who's one that I think has some of the most important and cutting-edge research on effects of diets, particularly on the long-term effects of diets. And when she started to study this in the year 2000, the science was very clear and gave very solid advice. Diets work. So she looked at this, and there were many thousands of studies demonstrating this. But she noticed something a bit weird about these, these studies. They followed people for three months. So you massively cut back your calories, you exercise more, you lose a shitload of weight. And at the end of those three months, it just assumes, "Well, now you'll live happily ever after at this lower weight." And there were, you know, a few thousand studies that also looked at people for six months and it found bro- they found broadly the same thing. But, but Professor Mann was like, "Well, I know quite a lot of people who've been on diets and a while down the line they're fatter than they were at the start. What's going on here?" So she looked at, "Well, what are the, what do we know about people who diet for like longer than that, for like two years for example?" At the time there were 24 studies on that. And when she looked at their results, it was completely different. If you diet for two years, you are at the end of it two pounds lighter than you were at the start. Which is not nothing, it is statistically significant, but it's shockingly low, right? So it's like, well what's going on there? What-

   4. CWChris Williamson32:37

      It's like-

   5. JHJohann Hari32:37

      ... what's happening?

   6. CWChris Williamson32:38

      ... 10 grams per week or something across-

   7. JHJohann Hari32:41

      Yeah.

   8. CWChris Williamson32:41

      ... the space of two years.

   9. JHJohann Hari32:43

      Exactly. It's, it's, it's n- it's, it's not a lot, right? She's like, "What's going on here?" (clears throat) And to understand this, uh, broad diet fallace, when you look at the wider evidence, there is a small subsection of people who diet and lose significant amount of weight and keep it off. I've got someone very close to me, family like that, everyone knows someone like that. But the evidence is pretty clear as well, in the longer term, they are statistical outliers, right? They exist, they're very real, it's certainly worth trying to be one of those people. But there are about 10 to 15% of people, right, who try dieting. And pretty much every fat person has tried dieting though, i- it's very rare you get one who hasn't. So what's going on with the others, right? What, what's happening? And to dig into this I interviewed loads of experts on it. And this is contested and much debated, but I think the evidence is pretty clear around one set of things. So if you go back to the '70s, before the obesity crisis happened, people were pretty sure they knew the science of this. They thought that when you were born, you had what was called a biological set point that determined your weight. Basically, your genes say what you're gonna be. And you know, you can go a little bit above it or a little bit below it, but not by much, right? If you think about your body temperature, you get a good analogy, right? Your body really wants you to be whatever it is, 40 degrees centigrade, right? It fixes your temperature at that. If you go above it, say you go to the Sahara Desert, it will make you sweat like a fucker to bring your body temperature down. It will make you crave shade. If you go below it, like you go to the Arctic, it'll make you shiver like a fucker to get your weight back up. Your body works extremely hard to keep you at that biological set point for your temperature. And they thought there was something similar for weight. You can try and go outside it, but your body will fight to bring you back to that set point. But then the obesity crisis happened, and the whole thing went out the window, 'cause if you had a fixed set point from birth, how could it be that, you know, obesity more than doubled in 20 years, right? It makes no sense. But then what scientists began, some scientists like Professor Michael Lough began to argue, is something a bit different. You do have a biological set point, but as you gain weight, your biological set point rises. So let's imagine that you gained like three stone now, Chris. Right? Please don't. It would be a tragedy for gays the world over. But if you did, um, your brain, in this theory, would then fight to keep you at that higher weight, and there's a lot of evidence for that. We know that if you gain weight and try to lose it, your metabolism slows down, so you burn calories more slowly, you crave more sugary, fatty, salty foods, uh, you're more lethargic so it's harder to exercise. These things are not impossible, you can overcome them, but it's a whole strain of obstacles. And the evidence for that is really clear, particularly metabolic slowdown, but I remember scientists kept explaining that to me, and after a while I said to a load of them, "This doesn't ring true to me because why would evolution endow us with such a, a maladaptation, right?" That's obvious, why would e- evolution make us, want us to be really, really fat when that kills you, right? Um, and Professor Lough and lots of other people explained to me, you've got to think about the circumstances where human beings evolved, right? In the circumstances where human beings evolved, the situation we now live in, where there are just a massive number of abundant excess calories all around you all the time for your whole life never happened, right? Or would have been extraordinarily rare. It certainly wouldn't have lasted over your whole life, right? So evolution didn't prepare us for this scenario because it never happened for the first 300,000 years we existed. What evolution prepared us for is a very different situation that existed frequently, which was the risk of famine, right? So you weren't at risk of being surrounded by calories, excess calories the whole time, you were at risk of calories running out at any moment and you being fucked. And you think about a famine, in a famine, the fattest guy at the start will be the last man standing, right? Timothée Chalamet will die in week one and me at my fattest will cry over his corpse and still be alive a month later, right? So you can see when you see it from that perspective, the circumstances of our evolution, why, as Dr. Giles Yeo, one of the leading obesity specialists in Britain put it to me, "Your brain..."...hates it when you lose weight, and will fight to drag you back to your highest weight. It's preparing you for a famine. But in our case, it's preparing us for a famine that will never come, right? Now some people argue that in the huge debate about... So I think that's why diets fail for most people, right? It's interesting to think about, well, what's going on with that minority who do manage to break it? We can talk about that. But for me, that also leads to an interesting debate about the drugs. Because there's a huge debate about, given the drugs work on your brain, we now know that, right? You give the drugs to rodents, and then you cut open their brain, what you see is these drugs go everywhere in the brain, right? Every part of the brain. And there's a huge debate about what they're doing in your brain. And it's slightly disconcerting to interview the leading neuroscientists, and they kind of go, "Well, we're not really sure." Uh, Dr. Clemence Bluey at Cambridge University said to me, "You know, the brain is the most complex object in the whole universe. It shouldn't surprise you that we don't entirely understand how it works." But one theory, and I stress it is a theory, and there are other theories disputing it, is that what these drugs do is it basically lowers your biological setpoint. It's the equivalent, to put it very crudely, of taking your iPhone back to the factory settings, right? It makes your brain stop fighting to bring you back to that higher weight.

   10. CWChris Williamson38:04

       Yeah, that's

7. 38:05 – 43:10

   Most People Are in an Unfair Fight

   1. CWChris Williamson38:05

      very interesting. I think, you know, it's a, it's an easy criticism, and we've had an unlimited number of people on the show talking about the benefits of diet and exercise and digging into the real nuances of exactly how you need to be timing your protein and what's the reps and sets and recovery and periodizing and MesoCycles and stuff. The research suggests that most people who start diets and try to lose weight through diet and exercise, don't. And, you know, you can say, and m- many people probably will, "These people just need to be less psychologically weak, they need more willpower, they're not working hard enough." It's like, but, uh, that's a, a fine rationale narrative to push forward, but like, ultimately, the evidence doesn't show... I don't, I don't know how much you can castigate or shame people into trying to lose weight. I don't know if that's going to work. Yes. Is diet and exercise a very reliable route out of this? Yes. Would it be best if everybody could do it through that? Yes. But does it seem to be a, like, reliable route to it not working over a two-year-plus time span? Also, yeah. And, uh, I, I kind of get the sense that given that we're in such a novel food environment, hyper-palatable processed foods, it has become an unfair fight for many people who perhaps 40 years ago would've been able to lose weight through diet and exercise, but the environment that they find themselves in now, their particular orification psychology is outgunned.

   2. JHJohann Hari39:31

      That's a really smart analogy. I mean, actually, what we know is that 40 years ago, they wouldn't have become fat in the first place. And if they did, they would've found it easier to get it off. But I think in terms of the willpower argument, I really like how you just framed that, Chris. In terms of willpower, so there are people who deny that willpower exists or can be used for weight, and that just obviously wrong, right? Willpower is a real phenomenon. It exists. Everyone listening will have ex- exercised willpower at some point in their life in relation to food, right? Of course, sometimes you turn down dessert or whatever. Even if you're the fattest person in the world, sometimes you say no to something, right? Um, but the way I began to think about willpower, because, precisely because it is real and it is important, is the way I think you have to look at willpower is i- is the environment in which willpower operates. I think you just framed it really well. So the kind of fancy way of putting it, the technical term, if you look at what causes obesity and actually lots of other problems like depression, anxiety, a whole lot of other things, is th- what's called the biopsychosocial model. It sounds technical, but it's actually very simple. There's three kinds of cause of this problem, like obesity. There's biological causes, right? Your genes can make you more sensitive to these problems. More importantly, there are biological changes that happen as you gain weight that make it harder to go back, like we've been talking about. So there's are biological causes. There are psychological causes that drive eating. We talked about comfort eating, for example. That's just one of them. If you're a man who loses his job, you way more likely to gain weight, and that's partly, like, just feeling like shit, 'cause you've lost your job and haven't got another one, right? And your sense of purpose. But there's lots of others. And then there's social causes, like the fact that we live in this completely, uh, as you say, a completely unprecedented food environment, right? So you think about the biopsychosocial model explains why we became obese. Where does willpower fit into that? Willpower is one sliver of the psychological component to it, right? It's very real. People with strong willpower, I really admire them. They deserve a lot of credit. It's a g- it's a good quality to have as a human being, not just in relation to food, but generally in life, right? But the way I think of it is, it's like an umbrella in a really powerful storm, right? Some people are gonna hold that umbrella, and they're gonna be able to get through the storm and get to their destination and be dry. But because the storm is so bad, 'cause of all these other factors, for most people, the umbrella's just gonna break, right? And you can slag them off and say, "You fool. It's your fault." But I don't know that gets us very far. I think you're right that we, we've gotta live in reality. We have tried just chiding people for 40 years, right? There will not be a single fat person listening to this who's not had a million times someone say to them, "Use some willpower, you fat..." Right? The, uh, the, uh, that message is every day, right? Um, if that, if the solution was to just urge fat people to have more willpower and pull themselves together, there wouldn't be a fat person left. In fact, you look at fat women in particular, women with a BMI higher than 35, 42% of them get insulted every single day. So the issue here is not the lack of insults or even the lack of well-meant advice about willpower, right? And, uh, and I actually separate, separate that, 'cause there is genuine well-meant... Th- there is shaming and stigma and all of that. A lot of it is very well meant, and a lot of it is useful, right? It, it, there's some truth in it, but it's one truth among a much more complex picture. The only thing I object to about that advice is if you act like it's everything that's going on. It's not everything, right? It's one small part of a bigger picture.

   3. CWChris Williamson42:56

      Talk to me about how GLP-1 agonists have effects on other behaviors, addiction, drugs, behavioral stuff, screen time, those stuff.

   4. JHJohann Hari43:07

      This is massively contested. Of all the areas

8. 43:10 – 47:17

   How the Drugs Impact Other Behaviours

   1. JHJohann Hari43:10

      that I write about in the book, this is the one where there's the least agreement. And that's saying something because there's a lot of debate about almost everything attached to these drugs. There's one thing we know for sure, these drugs have an extraordinary effect in animal studies on reducing the consumption of alcohol, cocaine, heroin and fentanyl. So, I interviewed the scientist who'd done the cutting edge research on this, give you an example. A brilliant scientist at the University of Gothenburg in Sweden called Professor Elisabet Jarlhag has done cutting edge research on this for 10 years now. So what you do is you get a load of rats, and it turns out rats fucking love alcohol, right? They drink it, they'll wobble about their cage, they look very happy. And so she gets these rats and gets them to use alcohol for quite a long period of time until eventually their, you know, their cage looks like a really rough dive bar in north Las Vegas. And then she comes along and injects them in the nape of their neck with a GLP-1 agonist. And what happens is that alcohol consumption massively reduces, by 50% in most of the studies, right? A quite remarkable decline. And interestingly, the rats who drank the most, that are kind of, it's a very rough terms, but the closest you'll get to an alcoholic in a rat, are the ones who cut back the most, right? But at first, with these studies people thought, "Okay, maybe it's..." Obviously we know these drugs reduce your desire for calories. Maybe it's because alcohol has a caloric component that, you know, that's why the drugs, that's why the rats drink less. So this was tried with drugs that aren't, don't have any calories in them. So Professor Patricia Grigson, who's the head of neuroscience at Penn State University who I interviewed, did this with rats with heroin and fentanyl. Again, massive decline in them using those drugs, self-administering those drugs. Ditto, uh, Dr. Greg Stanwood at Florida State University did cocaine with mice. Um, uh, got the co-, got a load of mice to use loads of cocaine. I imagine they went on long boring monologues. Uh, ga- gave them GLP-1 agonists, 50% reduction. And one of the things that's really striking about this, um, as Professor Heath Schmidt put it to me is, what's crazy is it works with all drugs. That's very unusual. You know, we have treatments for, you know, methadone that reduces heroin use, whatever. But to have something that seems to reduce all drug use across the board, that is unprecedented. The human research on this is interesting. So we have a lot of anecdotal evidence. So for example, I introdu- interviewed a woman called Tracy, a mental health nurse in Canada who had been a very heavy, um... She had a problem. She basically broke up from her ex-boyfriend and went on a kind of spending binge. So she would obsessively like buy clothes she wouldn't wear, buy books she'd never read. She was just spending... She got that real, you know, rush from clicking buy, buy, buy. She started taking Ozempic for her weight and just noticed all this compulsive shopping went away. So lots of doctors are having lots of patients report similar things. The actual studies in humans we have so far are very small and they're a bit of a mixed bag, surprisingly, and a bit disappointingly actually. Um, so we know they do reduce cigarette smoking but only if you combine them with a nicotine patch. No one knows why. We know they do reduce alcohol consumption, uh, but only in people who had a drinking problem in the first place. There's a shitload of studies going on now looking at these drugs, uh, in addiction. So we'll know a lot more soon, but the most, the most optimistic way of interpreting this, and we should say it with a lot of skepticism, this is quite speculative, but if you wanted to be really optimistic, some people looking at this evidence say actually this isn't a weight loss drug. This is a drug that boosts self-control across the board. Now we need a lot of evidence to back that up, that's a big claim. But I wouldn't rule it out. It's not impossible. I don't think it's likely, but it's not impossible.

   2. CWChris Williamson47:03

      I have a friend who is a huge, huge evangelist for all of the GLP-1s. He's on the s- is it tirzepatide I think? Which is this-

   3. JHJohann Hari47:12

      Yeah, correct. Yeah, tirzepatide, yeah.

   4. CWChris Williamson47:13

      Which is the second generation. And, uh, he told me a couple of

9. 47:17 – 52:38

   Main Risks of Taking These Drugs

   1. CWChris Williamson47:17

      weeks ago, uh, it turns out, turns out that willpower is just a drug and the dosage is around about 0.5 milligrams per day.

   2. JHJohann Hari47:23

      (laughs)

   3. CWChris Williamson47:23

      So, y- y- he- he's, uh, he's seen fantastic returns, I guess, from taking it. But talking about the light side, what about the dark sides? What are the main risks of taking these things?

   4. JHJohann Hari47:36

      Well, there are 12 big risks I go through in the book, but I'll give you an example of one. So when you talk to experts about the safety of these drugs, the first thing most of them say is a very good point that should give people some level of reassurance. They say, "Look, actually we've got loads of evidence about what these drugs do to people because diabetics have been taking them for 18 years." So for people who don't know, in addition to having these effects on your appetite, these drugs also stimulate the creation of insulin which is obviously what diabetics both type 1 and type 2 need. So, 18 years ago we started prescribing them all over the world. You know, hundreds of thousands of diabetics have been taking them. So what a lot of the experts say, "Look, if these drugs had some terrible short or medium-term effect, we would know by now. If they gave you horns, the diabetics would have horns by now, right?" But what some other ex- and that, that's a very good point. That's, there's a lot of legitimacy in that point. But what some other experts said, "Okay, if we're gonna base our conviction on the safety of the drugs largely on the diabetics, let's dig a little bit more into what's actually going on with the diabetics." So I'll give you an example. There's a brilliant scientist called Professor Jean-Luc Fahy who's at the University Hospital in Mon- Montpellier in France, who I interviewed. He was commissioned by the French Medicines Agency to investigate the safety of these drugs for the French market. So he looked at the, what's called the preclinical evidence, the experiments on animals first.... and was quite taken aback by something, which is if you give these drugs to rats, you really significantly increase their risk of thyroid cancer. And we know that you have GLP-1 receptors not just in your gut and in your brain, but in your thyroid. So there's a plausible mechanism cau- of causation there that, "Oh, if you're fucking with GLP-1, you might fuck with your thyroid," right? To put it in, uh, slightly unscientific terms. So he went to the French medical databases. They have really good medical databases you- 'cause you basically can't opt out of them in France. They don't have the equivalent of HIPAA. And he compared diabetics who'd been taking these drugs between, I think it was 2006 and 2016 if I remember right, with a comparable group of diabetics who were similar in every other way but had not taken these drugs. And what he found at first is pretty eye-catching. He calculated with his colleagues, if you take these drugs, you are increasing your thyroid cancer risk by between 50 to 75%. Now, he said to me, "Don't misunderstand that. That doesn't mean if you take the drug, you have a 50 to 75% chance of getting thyroid cancer." If that was the case, we'd be having bonfires of Ozempic all over the world. What it means is whatever your thyroid cancer rate was at the start, if he's right, and this is highly disputed, um, it will increase by 50 to 75%. Now, thyroid cancer is fairly rare. 1.2% of people get it in their life, 84% of them survive it. Nonetheless, it's a pretty big increase and a relatively small risk. But against that, you have to weigh, and this always comes back with all these risks, to what is the cancer risk just from being obese and continuing to be obese? I have to say, of all the things I learned for the book, I'm a bit embarrassed to say this, the thing that most shocked me was the thing I thought I had known since I was a little boy. I'm pretty sure at any point in my life, if you'd said to me, "If you're obese, is it bad for your health?" I would've said yes, right? From when I was, like, five or something. But I was stunned by the evidence for how bad obesity is for your health, or just being overweight, never mind obese, right? So think about it in relation to cancer. As Cancer Research UK, the biggest cancer charity in Britain, explains, if you carry excess weight, it doesn't just sit there in your body. It's not inert. It's active. It sends signals throughout your body. And one of the signals it can send is for cells to divide more rapidly, which can cause cancer. This is why obesity is, in fact, one of the biggest causes of cancer in the United States and Britain, right? Like, like, it's quite shocking, the figures, when you look at them. Um, and that's just one of an enormous array of effects of obesity. So whenever you're looking at the risks of these drugs, and that thyroid cancer is a very alarm- risk is alarming, and it's why, if anyone listening, if you have thyroid cancer in your family, I don't think you should take these drugs. If you, if you have any reason or certainly if you've had thyroid cancer before, you definitely shouldn't, anyone who has any reason to believe they're at risk of that, I would, I would say it should weigh very heavily on you, that risk. Um, but again, you, you gotta weigh it against the, the, the, what for a lot of people realistically will be the risk of obesity. Uh, as Dr. Shauna Levy, who's an obesity specialist at Tulane University School of Medicine in New Orleans, said to me, "You know, we don't know the long-term risks of these drugs, but we do know the long-term risks of obesity, and they are shocking."

   5. CWChris Williamson52:23

      I'm- I think I'm right in saying that rats or mice have a special type of receptor on their thyroids as well, so that some of the studies that are done on them aren't necessarily portable across onto humans in the same way. That was something

10. 52:38 – 55:04

    How Weight Loss Drugs Impact Muscle Mass

    1. CWChris Williamson52:38

       that I learned while I was away a couple of weeks ago. What about muscle mass? What does it do to muscle mass?

    2. JHJohann Hari52:42

       This is a really big issue. Um, so any form of weight loss, on average, causes a loss of muscle mass. Weirdly, that hasn't happened with me, but I think that's 'cause my muscle mass was so fucking puny at the start. (laughs) There was nothing to lose.

    3. CWChris Williamson52:52

       We'll get you in the gym. We'll get you in the gym going.

    4. JHJohann Hari52:54

       Exactly. You'll lure me there, Chris. You're the one of few people who could. Um, so what we know is most people shed mus- I know you know this much better than I do. Any form of weight loss generally causes a loss of muscle mass, which is the total amount of soft tissue in your body. Obviously, you need it for things like climbing the stairs, getting up out of the chair, you know, movement. Um, and we know that this is risky. It's not that risky if you're in your 30s or 40s, but as you age, you shed quite a lot of muscle mass each year. If you're going into the aging process with depleted muscle mass, low levels, it massively increases the odds that as you age, you'll develop a condition called sarcopenia, which means poverty of the flesh, which is basically where you just can't fucking do anything. You can't climb the stairs. You can't get out of a chair on your own. You're much more likely to fall over. If you f- do fall over, you're much more likely to die. And this is particularly worrying 'cause I would al- I would argue there's sort of two categories of people here. I mean, this is a very broad-brush statement, but there's people who are like that guy Jeff Parker I mentioned in San Francisco. There's people who are overweight or obese who are taking these drugs to come down to a healthy weight. I think that's very defensible. Although, plenty of people in that position look at the r- other 11 risks and think, "Well, it's not worth it for me." But that's very defensible. Then you've got people who are already a healthy weight or in fact are underweight who are taking it to be super skinny, right? We can all think, fill in name of famous actress here, right? Think about people at that party I went to. None of them were obese, right, at the start. Far from it. They are particularly incurring this muscle mass risk. That won't show up now, but it could really pose problems for their health as they age, and it could create a kind of ticking time bomb problem. A population where, you know, half the people are taking these drugs, that can have a real problem when people are aging if they're taking too high a dose or they're taking it to be super skinny.

    5. CWChris Williamson54:50

       What do you think the introduction of these drugs means in a world where people are more concerned with their appearance than ever before?

    6. JHJohann Hari54:59

       It's a complicated question.The worst moment for

11. 55:04 – 1:03:53

    Our Appearance-Obsessed World

    1. JHJohann Hari55:04

       me when I was working on the book... Was a moment with my niece. So she's, she's... I can't but, I can't bear to say this. She's 19 years old now, but she's the baby in my family. She's the only girl in her generation. So in my head, she's fixed as a six-year-old, right? Whenever she has a boyfriend, I always wanna go, "Get away from her, you fucking pedo." But they're always... (laughs) I'm like, "Oh well. She's an adult woman now." Um, and it... One day, I was saying, you know, mate, f- four or five months of taking the drugs maybe, I was FaceTiming with her. She was in a pub in Liverpool. And, you know, she was kinda teasing me, going, "Oh, I never knew you had a neck before. You know, I never knew you had a jaw," right? Uh, but saying I looked good, and I was kinda preening, and then she looked down and she said, "Will you buy me some Ozempic?" And I laughed 'cause she's, like, a perfectly healthy weight. And suddenly I realized she meant it, and I thought, "Fuck, what am I doing here?" Right? Am I counteracting all these messages I've given her since she was a little girl? And... We know that if you change the kind of, the body, the beauty norms... Particularly women are vulnerable to this. Well, men are vulnerable in a different way, 'cause men generally wanna become bigger, rather than becoming-

    2. CWChris Williamson56:12

       Bigger X, yeah.

    3. JHJohann Hari56:13

       ... smaller.

    4. CWChris Williamson56:13

       Yeah.

    5. JHJohann Hari56:13

       Exactly. Which I, uh, certainly, of course, as you know very well, has all sorts of problems that you discuss on your podcast. But that's a different thing, right? The, uh, so set that aside for a minute. I'm not worried that these drugs'll affect that. Um, although there are plenty of things to worry about in relation to that. With, with, with girls... So think, for example... A really weird fact. Between 1966 and 1968, the percentage of girls who thought they were fat exploded, the percentage of girls who th- were unhappy with their bodies, right? So a very short amount of time. You're like, "Well, what happened between 1966 and 1968?" What happened is there was a famous model named Twiggy who was just naturally extremely thin, um, who was sort of presented as, like, the face of beauty, the face of the '60s. And suddenly people looked at her and were like, "Well, shit, I don't look like Twiggy. I don't like my body," right? So we know when a body norm changes, um, a beauty norm changes, it can change, i- well, it changes how people feel about their bodies, right? Um, so I'm, I'm really worried for young girls in particular about what... I think about just even, like, my niece. All the actresses she likes or pop stars who were a little bit kind of broader range of body types, they're all fucking bone thin now. And by the way, they all claim that they're doing Pilates, or you know, I don't know, maybe there's been an outbreak of dysentery in Malibu or something. But you know, the, the... What's that doing? I mean, the biggest worry I have, if you said... Se- this is not a worry I have for myself, but if you said, "What is my single biggest worry out of the 12 for these drugs?" My biggest worry is what it'll do with eating disorders, right? So even before the pandemic, we had the highest level of eating disorders in the history of the United States and Britain, and then during the pandemic, it actually rose. That's obviously overwhelmingly young girls. It is some young boys, but it's mostly young girls. Um... We're in the, and it's a, a complex range of reasons, but I would say social media, loneliness, a whole range of th- range of things. People should read my friend Jonathan Haidt's excellent book, The Anxious Generation, for more insight on that. But, um... What my, m- what these drugs do... A- anyone who's known anyone with an eating disorder knows they're in a conflict. There's the psychological part of them that wants to starve themselves, and there's the physical part of them in their body that wants to stay alive and eat. And what these drugs do is give you an unprecedented tool to amputate your appetite, right? This is why eating disorders experts are extremely worried about, uh... People like Dr. Kimberly Dennis, one of the leading eating disorders experts in the US who I interviewed, are extremely worried about, you know, this could produce an opioid-like death toll of very large numbers of young girls who would not have been able to kill themselves without these drugs you are... Now, there's something we can do to massively reduce that risk, which is, at the moment, anyone listening, you can just go online and get these drugs on Zoom. You see a doctor on Zoom. Well, that's... How well is a doctor able to assess your BMI on Zoom? Not very, right? So Dr. Dennis argues, I think very persuasively, you should only be able to get these drugs from in-person appointments with doctors who are trained in spotting eating disorders. Obviously if you have a BMI lower than 27, they should not give it to you.

    6. CWChris Williamson59:26

       Mm.

    7. JHJohann Hari59:27

       And if they suspect you have an eating disorder, they shouldn't give it to you.

    8. CWChris Williamson59:29

       Right. Because p- people are basically enhancing their ability to access malnutrition.

    9. JHJohann Hari59:35

       That's a brilliant way of putting it. That's exactly right. And malnutrition is a huge, huge risk here. Um, that, that's exactly correct.

    10. CWChris Williamson59:43

        What happens if you stop taking it?

    11. JHJohann Hari59:46

        There's a bit of a debate about this, and we don't have a lot of good evidence. It looks like you regain all the weight pretty quickly. Uh, there does seem to be a subsection of people who use it to interrupt their habits, develop new habits, then come off the drug and remain at a lower weight. But w- people have only been using this for obesity for a couple of years. We basically don't know. Uh, what the drug companies are saying... And bear in mind, they obviously have a strong vested interest in wanting you to take it forever because they get more money the more you buy. Um, they say it's like blood pressure medications, it's like statins. They work as long as you take them. You stop taking them, they stop working. That d- does seem to be the case for most people.

    12. CWChris Williamson1:00:25

        I wonder how many people are going to be confronted with a bit of an existential crisis when they lose a ton of weight by taking these drugs, and it's revealed to them that being overweight wasn't the root of all of their psychological problems, because you're now skinny but still miserable.

    13. JHJohann Hari1:00:44

        I think that's a really important question. Carell L'Heureux, who I mentioned before, I think, a brilliant, um, expert in, uh, bariat- who, who's also done a lot of work on bariatric surgery, he said he thinks that's one of the reasons why the suicide rate goes up so much after bariatric surgery. That a lot of people imagine, "What's wrong with my life is that I'm fat."... and if I was thin, I'd be okay. And then they lose all this weight, and their husband's still a prick, and their job's still shit, and their life isn't what they wanted it to be. And it's, they're forced to confront, "Oh, actually, while this may, well, obviously have benefits for their physical health, it's not resolved all these problems magically," right? I, I do think there's, um, there's a lot of truth in that.

    14. CWChris Williamson1:01:27

        What about women who are either going to become pregnant, trying to become pregnant, are pregnant? Is there dangers for them?

    15. JHJohann Hari1:01:35

        Yes. So what we know, again, in animal models, is rats who get pregnant when take, when they're taking these drugs or given these drugs, in the case of rats, are much more likely to have children with birth deformities. Um, you're advised to not take these drugs if you're trying to get pregnant, but of course, some people will just accidentally get pregnant or whatever. I'm, I'm worri- I'm quite worried about that. And it could be that there's some immediate short term effect, but that seems unlikely because it would've probably shown up in the diabetics by now. What people like Dr. Greg Stanwood at Florida State University are concerned about, and he stressed this is speculative 'cause by, uh, definition we don't know, he said he's, has some concern that there may be a parallel. Look at what happens to pregnant women who are exposed to environmental contaminants like lead, for example. When their babies are born, their babies appear to be like everyone else. But when their kids get to go through adol- become adolescent, they seem to have poorer regulation control, poorer, um, attention, that it turns out that that exposure to lead in the womb has had an effect on them that only emerges later. He said, and he stressed it was speculative, but he said he is concerned we should keep an eye on the possibility that will be the case with these drugs.

    16. CWChris Williamson1:02:50

        Well, I mean, the natal, the natal environment is, uh, every time that I learn something about it, it blows my mind.

    17. JHJohann Hari1:02:56

        Yeah.

    18. CWChris Williamson1:02:56

        Robert Sapolsky did this great study where I think some of his colleagues looked at women who enter poverty during pregnancy. Poverty is a very reliable source of stress. And, uh, it's crazy. Like, and the, the other thing to consider is if a woman is pregnant with a female, she is also pregnant with every egg that that female fetus is ever going to be able to produce. So, you were inside of your grandmother at one point...

    19. JHJohann Hari1:03:23

        Whoa.

    20. CWChris Williamson1:03:23

        ... which I'm sure is something you've thought about a lot.

    21. JHJohann Hari1:03:25

        (laughs) Exactly. Yeah. Who, who told you my web browser?

    22. CWChris Williamson1:03:28

        (laughs)

    23. JHJohann Hari1:03:28

        Who told you my Pornhub search history? Damn it.

    24. CWChris Williamson1:03:31

        But yeah, you know, the, the, the cascade sort of carries. And, and, yeah, it's, um, it's a concern. It r- it really is.

    25. JHJohann Hari1:03:38

        Yeah.

    26. CWChris Williamson1:03:39

        So, where did you come into land with this? After taking it yourself, after speaking to experts, after looking at the state of our diet and ultra-processed foods and science and all the rest of it, how have you come to weigh the scales of the GLP-1s?

12. 1:03:53 – 1:10:52

    Johann’s Thoughts After Writing the Book

    1. CWChris Williamson1:03:53

    2. JHJohann Hari1:03:53

       Yeah, the book is called Magic Pill 'cause there's kind of three ways these drugs could be magic. They could just solve the problem, right? In a way that is so swift that it feels like magic. And I've gotta tell you, Chris, there are days it feels like that. My whole life, I've eaten way too much and I've eaten shit. And now I inject myself once a week in the leg, a tiny little mosquito bite-like feeling, and I eat radically less and I eat differently. That feels like magic, right? The second way in which it could be magic is it could be like a magic trick, an illusion. It could be like a, you know, a magician who shows you a great card trick while picking your pocket. It could give you these benefits but fuck you over in the longer term. I don't rule that out. The third way, actually 'cause it's the most likely, if you think about the classic stories about magic that we grew up with, think about Aladdin, right? You find the lamp, you rub it, the genie appears, and you get to make your wishes. And your wishes come true, but never quite in the way that you expected, right? Think about Fantasia. You unleash the magic and it runs away from you in all these unpredictable and chaotic ways. I think it's probably gonna be like that. It'll probably gonna have some good stuff and some bad stuff. In terms of personal advice, it, I have to say it's disconcerting to have been on this huge journey, to have gone all over the world, to have interviewed all the leading experts, to learn so much, including a lot we haven't covered, and still not be able to give you all my other books. I've kind of come to a conclusion, like, "Well, dear reader, I think we should do the following, you should do the following three things, and as a society, we should do the following five things, and here's the stuff we can do, and here's how we can solve this problem." I don't really feel like that. Uh, I end the book by talking about five possible scenarios for how this could sh- turn out now. Um, and they really range very widely from the super pessimistic, this could be like Fen-Phen, the '90s disaster drug. We could discover some catastrophic effect. I don't think that's likely, but I don't think you can rule it out. Um, or it could be that the drugs work in the long term, the benefits outweigh the risks. We get them to everyone who needs them. That's a big shift, 'cause at the moment only tiny numbers of rich people can get them. Um, and crucially they fucking wake us up to go, "How did we end up with this? How did we end up having to choose between a risky drug and a risky medical condition? Is this what we fucking want for our children? Or shall we look at Japan, where they never had an obesity crisis and there is no market for these drugs because almost nobody is obese," right? And I went to Japan, I learned how they did that. That's what I hope will happen, that, that final scenario, but I don't really know. If you ask me for purely personal advice, and I wanna stress I am not a doctor, I'm a journalist, people should talk to their doctors, but having looked at all this evidence, and I give this evidence with a l- I, I give this advice with a low level of confidence. So you might wanna sue me in 20 years for giving it to you.

    3. CWChris Williamson1:06:44

       Mm-hmm. Mm-hmm.

    4. JHJohann Hari1:06:44

       But if your BMI is lower than 27, I would say you definitely shouldn't take these drugs. You're incurring all the risks, like to your muscle mass, for no benefit th- apart from an aesthetic one. If your BMI is higher than 35, I... If you were someone I loved, I would urge you to take the drugs. But if- if- assuming that you've tried dieting and it hasn't, you know, you haven't been able to keep the weight off. Because for me...The evidence is so clear that the risk of being obese at that level is so great. Even things like, I'm really embarrassed to say, I didn't know this, think about diabetes. If you're obese when you're 18, you have a 70% chance of getting diabetes in your life. But I always thought, "All right, it's not good to have diabetes, but if you live in a country where you get good healthcare, you get given insulin, you're basically like everyone else, right?" That is not the case. If you're interviewing doctors, like people like Dr. Max Pemberton, one of the most high profile doctors in Britain, Jesus, the facts are shocking. Diabetes knocks 15 years off your life. It is the biggest cause of preventable blindness. More people in the US have to have a limb or extremity amputated because they got diabetes than because they got shot. And you will have noticed, there ain't a shortage of people getting shot in the United States, right? Um, and that's just diabetes. I mean, Dr. Pemberton said to me, "As a doctor, if you gave me a choice tomorrow between becoming diabetic or becoming HIV positive, no contest, I'd choose to become HIV positive."

    5. CWChris Williamson1:08:13

       Oh, wow.

    6. JHJohann Hari1:08:13

       "If you get HIV and you get treatment, you live as long as everyone else." That is absolutely not the case with diabetes. You die sooner and you're much more likely to have a horrific last few years of your life where you are blind, demented, h- lose a limb, agonize. I mean, it's really... And that's just diabetes, right?

    7. CWChris Williamson1:08:34

       Mm-hmm.

    8. JHJohann Hari1:08:34

       So, if your BMI is higher than 35, that would be my advice. If your BMI is between 27 and 35, I think it's a much harder judgment call, and I would recommend you go through the risks of obesity in the book, the risks of the drugs in the book. Really think about which one is more likely to play out for you, and really what your risk appetite is, right? Different people have different... I have great respect for people who come to very d- And one of the things I've really liked about the reaction to the book so far is some people read the book and go, "I really like this book. You've made me be convinced that I must go out and get these drugs tomorrow." Other people have said to me, "I really like this book. You've made me convince you'd be fucking insane to take these drugs," right? It's a bit like, what was The Dress, where some people saw it as, what did they see as blue?

    9. CWChris Williamson1:09:18

       The blue and green or the black and gold or whatever. Mm-hmm.

    10. JHJohann Hari1:09:20

        Yeah. Exactly. I saw it as black and gold, right? The, um, it's a bit like that. I'm fascinated by how people read the book and come to completely different conclusions and are absolutely convinced that I shared their secret conclusion-

    11. CWChris Williamson1:09:31

        Mm-hmm. Mm-hmm.

    12. JHJohann Hari1:09:31

        ... all along. So I feel like it makes me feel like I sort of did my job right, but there, I think we don't know. One thing I'm completely confident of is the stakes here are unbelievably high. This is, by some measures, the biggest cause of death, preventable cause of death, in our societies, right? Gerald Mann, who I mentioned before at Harvard, says obesity and foods cau- food-caused illnesses kill 678,000 people in the United States every year. That's all the wars of the 20th century for American soldiers combined, plus some, right? Every year. So, whether we get this right will determine whether lots of people live or die. I think these drugs are an interesting and important tool. The way I think of it is for a lot of us, we're in a trap, and this is the rusty, risky trap door we're being offered. We've got to change up the way our society works so we're not in this fucking trap. And we can change it so that our kids really won't be in this trap. We can do that. I go through how we can do it. I've been to places that have done it. But for now, we're facing a pretty shitty decision and we've got to think it through in detail.

    13. CWChris Williamson1:10:38

        Johann Hari, ladies and gentlemen. Johann, where should people go if they want to keep up to date with everything that you're doing?

    14. JHJohann Hari1:10:43

        Oh, uh, they go to my website. It's johannhari.com. If they want to know more about where to get the audiobook, physical book,

13. 1:10:52 – 1:12:24

    Where to Find Johann

    1. JHJohann Hari1:10:52

       or e-book, you go to magicpillbook.com. I meant to say you can get it from all good bookshops, but the truth is, you can get it from shit bookshops as well. We don't have like a quality test, you know. (laughs) But, um, but yeah, I'm very glad... I don't know if I said this to you last time I spoke to you, Chris, if it had already happened or not, but I had this really unfortunate, um, moment at the end of a podcast. Um, it must've been a couple of years ago. It was probably before we spoke. I was interviewed by someone, I won't say who, but it's a quite high profile podcast, and at the end of it, the guy said, "What's your Twitter?" And I said it. And he said, "What's your Instagram?" And I said it. And he said, "What's your Facebook?" And I said it. And then he said, "What's your Snapchat?" And I said, "I am a 45-year-old man. The only 45-year-old men on Snapchat are certainly pedophiles, right? Why else would they be on there?" And he didn't laugh at all, and I've got a bad habit of if someone doesn't laugh at my jokes, I lean into it more. So I said, "You know that TV show To Catch a Predator where they sort of catfish pedophiles?" I said, "The next season of To Catch a Predator should be they just go up to adult men in the street and say, 'What is your Snapchat handle?' And if they've got one, fucking throw them in the van, right? That's it. Immediate imprisonment." He didn't laugh at that. I later looked him up and he's quite active on Snapchat. So my goal now-

    2. CWChris Williamson1:12:00

       Ah.

    3. JHJohann Hari1:12:00

       ... with all podcast interviews is to get through it without accidentally accusing the host of being a pedophile. So-

    4. CWChris Williamson1:12:05

       Right, well, so far, so good.

    5. JHJohann Hari1:12:07

       Hooray.

    6. CWChris Williamson1:12:08

       Congratulations.

    7. JHJohann Hari1:12:08

       Thanks so much, Chris.

    8. CWChris Williamson1:12:10

       Johann, I appreciate you.

    9. JHJohann Hari1:12:10

       Oh, cheers. Really enjoyed, always enjoy talking to you. You ask really good questions. Thanks, Chris.

    10. CWChris Williamson1:12:13

        Thank you. If you enjoyed that episode, you will love a selection of the best clips from the podcast over the last couple of months, and it's available right here. Go on, give them a watch.

Episode duration: 1:12:24