Miracle Drugs & Quick Fixes with Dr. Nick Tiller

Is there such a thing as a quick fix? Neil deGrasse Tyson, Chuck Nice, and Gary O’Reilly learn about the science behind a wave of new weight loss drugs, the ethics of Ozempic use, and off-label prescriptions with exercise scientist, Dr. Nick Tiller.

Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.

• 0:00Neil deGrasse Tyson?

  Coming up on StarTalk, our guest is Dr. Nick Tiller, is an exercise physiologist, and we talk about the use of off-label drug prescriptions like Ozempic and other life-changing downstream benefits they might hold. In that case, it's weight loss, but might it also curb addiction of any kind? Is there such a thing as a quick fix? All that and more, coming up on StarTalk.

• 0:31Neil deGrasse Tyson?

  Welcome to StarTalk, your place in the universe where science and pop culture collide. StarTalk begins right now.

• 0:43Neil deGrasse Tyson?

  This is StarTalk. Neil deGrasse Tyson here, your personal astrophysicist, and this is special edition, where we're going to be talking about medical quick fixes. I got with me my two co-hosts, Gary, Gary O'Reilly. How you doing, man?

• 1:00Gary O'Reilly?

  I'm good, Neil.

• 1:01Neil deGrasse Tyson?

  All right.

• 1:02Gary O'Reilly?

  To be on.

• 1:02Neil deGrasse Tyson?

  Former soccer pro and sports commentator, professionally, and we, they lend him to us for this purpose. Of course, we got Chuck Nice. Chuck, how you doing, man?

• 1:12Chuck Nice?

  Hey, buddy. What's happening?

• 1:13Neil deGrasse Tyson?

  Longtime co-host and you're comedian and actor. So Gary, you and your producers, like, think this stuff up. So clue me in what today's about.

• 1:24Gary O'Reilly?

  In a previous episode, we explored quick fix solutions in the health and wellness industry and

• 1:30Neil deGrasse Tyson?

  Scotch.

• 1:31Gary O'Reilly?

  Yes.

• 1:31Neil deGrasse Tyson?

  Us fixes everything.

• 1:33Chuck Nice?

  Boom, there you go, buddy.

• 1:34Gary O'Reilly?

  And we're not, we're not talking tape.

• 1:36Chuck Nice?

  And we're out. Quick fix, Scotch for everything in life.

• 1:42Gary O'Reilly?

  Okay, that and 420. So this show basically was a must-do because right now, the quickest fixes in town are weight loss drugs, Ozempic and Wegovy, depending on your preference. So that's our point of entry. And from there, we'll go off-label on a journey that I think we'll find pretty interesting. And today's guest is, it's fair to say, A skeptic has been on before. So Neil, introduce our guest, please.

• 2:09Neil deGrasse Tyson?

  Oh, Dr. Nick Tiller, who's it's the second time on StarTalk.

• 2:13Chuck Nice?

  A returning champion.

• 2:15Neil deGrasse Tyson?

  Returning champion.

• 2:16Speaker 03

  A repeat offender, you could say.

• 2:18Neil deGrasse Tyson?

  Oh, there you go.

• 2:19Speaker 03

  Residivist.

• 2:20Neil deGrasse Tyson?

  And I I realized you existed upon seeing the cover of your book, The Skeptic's Guide to Sports Science. So I know there's so much woo woo and and pseudoscience circulating in that community. And I said, we got to get this guy on the show. So.

• 2:37Chuck Nice?

  You had you had him at skeptic.

• 2:40Chuck Nice?

  The moment he saw skeptical.

• 2:41Neil deGrasse Tyson?

  What you're skeptic.

• 2:43Chuck Nice?

  He's like.

• 2:44Speaker 03

  That was a try. I used that word very, very precisely. I knew what I was doing when I when I titled it that. Yeah.

• 2:49Neil deGrasse Tyson?

  You've got it. So you you you have a PhD in respiratory functions of human physiology. You're a senior research fellow in exercise physiology at Harbor UCLA Medical Center. Very cool. Leading authority on physiology and pathophysiology. Love that. An extreme exercise, being an ultra marathoner and triathlon yourself. You would call that extreme exercise for sure. You're a columnist also for Skeptical Inquirer magazine, my single favorite magazine in the world. Let the record show.

• 3:25Chuck Nice?

  Oh.

• 3:25Neil deGrasse Tyson?

  Yes.

• 3:26Speaker 03

  Praise indeed.

• 3:27Neil deGrasse Tyson?

  I wait for it to show up and I say, how are people miss thinking things today? And there it is. And then they show it. So so Nick, welcome back to StarTalk.

• 3:37Speaker 03

  It's great to see you guys again. Thanks for having me back.

• 3:40Neil deGrasse Tyson?

  Yeah, yeah. So so Nick, let's just let's just go straight out. All right. I every day I find myself reciting the jingle for Ozempic. Okay.

• 3:53Speaker 03

  Can you imagine? So could you imagine if it was Wegovy and they started with wee wee wee? It just wouldn't be as good. Wouldn't be as good, would it?

• 4:02Chuck Nice?

  Okay. Let me tell you, I have a 10 year old daughter and for the last two years now, she walks up to me and I and it still gets me. And she goes, knock, knock. I say, who's there? She goes, oh, I say, oh, who? And she goes, oh, oh, oh, and I'm like, really?

• 4:18Speaker 03

  Good marketing, huh?

• 4:20Chuck Nice?

  I'm like, damn, you were watching too much TV, girl.

• 4:24Neil deGrasse Tyson?

  I expected better for her as the daughter of a comedian. Just thought I'd put it out there.

• 4:28Chuck Nice?

  Oh, yeah, maybe I'm not that good of a comedian.

• 4:33Neil deGrasse Tyson?

  We've heard a lot about this. I knew it had some relevance to diabetes, right? For diabetes patients. And then people started losing weight, losing their cravings. And I know people, it's an expensive drug, and I know some rich people. And apparently, this is just in their regimen, their weekly regimen. So it feels like a wonder drug, another quick fix. So how do we go from type 2 diabetes to a weight loss drug? How does that happen?

• 5:05Speaker 03

  Well, I guess Ozempic was FDA approved. So any drug that comes onto the market has to be approved by the Food and Drug Administration. So the FDA approved this in 2017 as a treatment for type 2 diabetes. So type 2 diabetes is when people produce insulin from the pancreas, but they're insulin resistant. So the insulin that they're producing is not exerting its effects on the body. And of course, insulin's function is to extract glucose from the blood to keep blood glucose levels within a very narrow homeostatic range.

• 5:39Neil deGrasse Tyson?

  And glucose is synonymous in that example with energy driving your body needs, correct?

• 5:44Speaker 03

  Right, absolutely. Glucose is just a simple carbohydrate. So any type of carbohydrate generally will cause your blood sugar levels to rise to some extent.

• 5:53Neil deGrasse Tyson?

  So it's one of that family of Osis, right? There's sucrose, fructose, glucose. So they're all sugars, right?

• 6:00Speaker 03

  Yeah, they're all sugars. Glucose is the simplest form of sugar. It's a single molecule. Fructose is another one. It's a single molecule. Sucrose, what we call table sugar, is a disaccharide. So it's glucose and fructose bound together. But essentially, they all get absorbed through the intestine, enter the blood, and they're going to cause a rise in blood glucose. People with diabetes can't control their blood sugar because of the reason that I just mentioned, that they're either not producing enough insulin.

• 6:27Neil deGrasse Tyson?

  That's type 1.

• 6:28Speaker 03

  That's type 1. Type 2 diabetes, they're producing it, but it's not potent enough. It's not exerting its effect. If blood sugar gets too high, it can cause systemic inflammation and all sorts of other problems. And if your blood sugar falls too low, it's difficult to stay conscious generally. So your body, your body will try, your body will try to maintain.

• 6:50Neil deGrasse Tyson?

  If my glucose is too level, yeah, you won't. You don't know because you're unconscious. Right.

• 6:54Chuck Nice?

  Well, yeah.

• 6:55Speaker 03

  Whoever's in the room with you will know because you'll be lying horizontal on the floor.

• 6:58Neil deGrasse Tyson?

  Okay.

• 6:58Speaker 03

  So your body will do whatever it can to maintain your blood sugar levels within this kind of narrow, normal, this homeostatic range. So this drug that we call Ozempic, it's called, it's called a GLP-1 agonist. And GLP-1 is glucagon-like peptide 1, has a very important role in the body. That when we take in some food, particularly if the food contains fats and sugars, will stimulate the release of GLP-1, which acts on the pancreas, which then stimulates, which then releases insulin. Is there another, is there a term for the drug? Is it, I mean, we're calling them GLP-1s, but, and they've got brand names. What, so what is semaglutide?

• 7:41Speaker 03

  So, so the drug itself is called semaglutide and the brand name is Ozempic. So that's what's actually branded and then FDA approved to treat type 2 diabetes. But shortly after these drugs were being prescribed to people with type 2 diabetes, physicians and scientists found that one of the side, I mean, you can call it a side effect or an additional effect, was that people were losing weight as well, which is generally good because people with type 2 diabetes are often overweight. Or if you're obese, if you're clinically obese, it predisposes you to type 2 diabetes. And so after a couple of years, the, the drug was prescribed by physicians off-label, which I guess we're going to talk about in a little while, to help people with weight loss.

• 8:25Speaker 03

  And then in 2021, the FDA re-approved semaglutide under a different brand name, Wegovy, specifically to help people to lose weight. But it works via the same kind of mechanism.

• 8:37Neil deGrasse Tyson?

  So what, it seems to me there's an interesting backdoor here that you're describing. Because if FDA approves a drug for whatever reason, and you find another application for that drug, it doesn't have to be FDA approved again. Is that correct?

• 8:52Speaker 03

  That's correct.

• 8:53Neil deGrasse Tyson?

  As long as your, as long as your doses are within the range of the originally intended dose, it doesn't have to be tested.

• 9:00Chuck Nice?

  That's why everybody loves the little blue pill.

• 9:04Speaker 03

  You're right. Well, and that was, that's an interesting one, actually.

• 9:07Chuck Nice?

  Be quiet, Chuck.

• 9:08Speaker 03

  Because, well, that, that was, when that was originally discovered, it's, um, I've got, I've written down some of the drug names here. Sodanefil citrate, because I can't remember the drug name. But sodanefil citrate was discovered because researchers were looking at ways to lower blood pressure.

• 9:22Chuck Nice?

  Right.

• 9:22Speaker 03

  And they found that this blood pressure lowering drug had this unintended side effect, that it increased blood flow to the male genitalia. So they rebranded it as Viagra. And the, and the weird thing is, they now prescribed Viagra off-label to treat high blood pressure.

• 9:38Chuck Nice?

  That's right. That's right.

• 9:40Speaker 03

  It's gone full circle.

• 9:41Chuck Nice?

  It's gone full circle. So weird. So what is it about carrying extra weight, specifically subcutaneous belly fat, that leads to diabetes? What is that association?

• 9:53Neil deGrasse Tyson?

  I never knew the answer to that myself. So, yeah.

• 9:56Chuck Nice?

  What is going on there?

• 9:58Speaker 03

  Right. So belly fat is more metabolically active and it's closer to your viscera, to the internal organs. So if you have a large amount of belly fat, it's more likely to penetrate deep into the, into the viscera and so, and surround your pancreas and your, and your liver and so forth.

• 10:11Chuck Nice?

  Ooh.

• 10:12Speaker 03

  So because this fat is more metabolically active, it is, it has a much more, a much closer association with disrupted blood, blood, blood sugar control and signaling. So, and this is a problem for men especially, because I don't know if you've noticed this, but men tend to store more of their body fat around the midsection.

• 10:30Chuck Nice?

  Yeah.

• 10:30Speaker 03

  Women in general tend to store more of their body fat around their hips and bums.

• 10:35Chuck Nice?

  Oh, they get, they're so lucky.

• 10:37Speaker 03

  Well, and in, in effect, they are, because it's the, it's the fat, it's the visceral fat, the central adiposity, which predisposes, as you say, to type 2 diabetes.

• 10:46Neil deGrasse Tyson?

  So that means men are more prone to type 2 diabetes than women, based on this analysis?

• 10:50Speaker 03

  Men who have greater waist to hip ratios, yeah.

• 10:54Neil deGrasse Tyson?

  Right, right, right. So Chuck, we need Sir Mix-a-Lot to do a song about men's belly fat.

• 11:00Chuck Nice?

  That's right. I like big guts in a can of nuts.

• 11:06Gary O'Reilly?

  All right. So Nick, when patients being treated for type 2 diabetes with the, I call it semaglutide, but semaglutide, it's a tomato, it's a tomato, whatever.

• 11:18Speaker 03

  That's because you're English.

• 11:18Gary O'Reilly?

  I know, sorry. But I don't apologize for that. The thing is. You just did. I take it back. This is not the apology you're looking for. So, so looking at that and saying to you, is there enough clinical evidence to back up this downstream off labeling of this drug as another use? Or is it, you know, was it enough of, you know, what doc lost weight? Fabulous. Great. Or is it just got to go clinically? How do you, how do you process this for this drug to come again as in another way?

• 11:53Speaker 03

  Yeah. So the only similarities between the two approval processes is that semaglutide, semaglutide has already gone through the phase one and two trials, which are essentially about making sure that administering the thing is not going to cause toxic downstream effects. So the safety profile is kind of already sort of in place, but they'll, they'll study independently for the independent effects. And there are dozens and dozens of very, very good randomized controlled trials that have looked at this independently in terms of treating type 2 diabetes, because it helps control blood glucose, and independently using semaglutide for weight loss, because it is a slightly, I guess you could say it's a slightly different mechanism. So, so you have GLP-1, it has a bunch of different effects

• 12:38Speaker 03

  on the body. Wherever there's a concentration of GLP-1 receptors, then GLP-1 is going to ex- its effects. So the first place that we have receptors is obviously in the pancreas that we've just discussed. So GLP-1 helps to upregulate the secretion of insulin, and it helps the beta cells of the pancreas, which actually does the secreting of insulin to proliferate. And it's sort of, they increase in number. So it can actually help to treat type 2 diabetes in that way. But we know that GLP-1 also acts on the stomach. And it does so in a way that suppresses the amount of gastric acid that's being secreted into the stomach. So obviously, when you when you take in food, you swallow the food down into

• 13:20Speaker 03

  the stomach, it comes into into contact with these different lipases and different enzymes to break down the food and hydrochloric acid. It turns the food into a into a mushy sludge and empties into the small intestine. And GLP-1 actually- Evidence of that, just look at anyone's throw up. Yes. Right, exactly. It turns it into that stuff. Yeah. And but but it but it does so in a way that it it suppresses the amount of gastric acid that's secreted. So it takes longer to break down the food and it slows the rate of gastric emptying. So you essentially stay fuller for longer. Mechanically, you keep more food in your stomach. So it helps to suppress appetite in that way. But there's a there's one other mechanism that's really important that we have to mention, and that GLP-1 also acts

• 14:05Speaker 03

  on receptors in the brain. So the hypothalamus is the is the body's kind of appetite control center. And by stimulating GLP-1 receptors in the hypothalamus, then we can actually reduce appetite, increase feelings of satiety, and people want to eat less.

• 14:23Chuck Nice?

  So is it true, or is this correlation rather than causation, that it not only reduces appetite for food, it reduces the other cravings and appetites, including alcohol and, you know, like sugar cravings and-

• 14:41Speaker 03

  Suppressing urges.

• 14:42Chuck Nice?

  Urges. Very good. Thank you.

• 14:44Speaker 03

  Is that where the brain part of this comes in?

• 14:45Chuck Nice?

  Is that true?

• 14:47Speaker 03

  It's probably not just correlation. It probably is causation. The reason that I say probably is because this all started because patients who were prescribed semaglutide for one reason or another were coming back to their doctors, saying, you know, it's not just that I want to eat less food, but my cravings and my typical addictions like alcohol or even cigarette smoking have also been suppressed. So so then we started to look at this under controlled conditions. There have been a bunch of studies now, mostly in rodent models, so in rats and mice, and a couple of studies in non-human primates. And what we think is happening, the mechanism hasn't been fully unpacked, but what we think is happening is that-

• 15:27Speaker 03

  That GLP-1 acts to down-regulate dopamine transmission in the brain. And dopamine, as we know, has a root central.

• 15:35Neil deGrasse Tyson?

  By the way, we have an entire episode on dopamine. So if people want to look into our archives, it's there.

• 15:39Speaker 03

  Absolutely. And when we eat some kind of food, particularly if it's tasty food, it contains lots of fat and sugar, the stuff that tastes really good, right? We get a dopamine spike in the brain that makes us, it gives us kind of a nice sensation. It reinforces food-related urges and reward-seeking mechanisms. And by down-regulating that pathway, then GLP-1 can, in theory, help to improve impulse control and decrease reward-seeking behavior. And that would be for whatever stimulates dopamine.

• 16:13Neil deGrasse Tyson?

  So Nick, I have some friends who are foodies, but like high-level, high-profile foodies, seeking out the finest chefs in the finest restaurants. Those who went on Ozempic, they noticed not only did they eat less, but they were deriving less enjoyment from the food.

• 16:32Chuck Nice?

  This isn't James Beard-worthy.

• 16:35Neil deGrasse Tyson?

  It was a double effect. It's like, not only am I not really hungry, I don't even want it. And so some of them were worried that it was subtracting away from them, this big part of their social life, going out and enjoying fine foodie-type things prepared by high-profile chefs.

• 16:54Chuck Nice?

  You call this a Michelin star meal?

• 16:58Speaker 03

  It's one of those repercussions.

• 16:59Neil deGrasse Tyson?

  But you didn't need a tangible Ozempic rating of the meals.

• 17:02Speaker 03

  Right. It's one of those repercussions that you don't even think about. But yeah, I guess we have to frame this in the context that there are two types of feedings. There's what we call homeostatic feeding. And then there's hedonic or hedonic feeding. And they're self-explanatory. But homeostatic feeding is when we eat because we, you know, we haven't had enough calories.

• 17:22Chuck Nice?

  You've got to survive.

• 17:23Speaker 03

  You've got to survive, right?

• 17:24Chuck Nice?

  Eat to live, not living to eat.

• 17:26Speaker 03

  If you go out and do a hard training session or you haven't eaten for a number of hours, then you're going to have a negative calorie deficit. So your body's going to tell you to go and eat more.

• 17:36Neil deGrasse Tyson?

  And that's called homeostatic.

• 17:38Speaker 03

  Homeostatic feeding, exactly, just in an effort to maintain normal dynamic equilibrium.

• 17:43Neil deGrasse Tyson?

  By the way, the way you word that, it sounds like we're zoo animals, okay? It's your feeding.

• 17:47Speaker 03

  In a way. Let's not tug at that thread.

• 17:50Neil deGrasse Tyson?

  Okay.

• 17:51Speaker 03

  And so hedonic feeding is literally, is chasing that reward, is that reward-seeking behavior, the food that makes us feel good, and that explains how we can go and have a huge Thanksgiving meal, have a big full stomach, and still find ourselves going back to get a second helping pumpkin pie.

• 18:07Neil deGrasse Tyson?

  Dessert, yeah.

• 18:08Speaker 03

  Because we don't need the calories, but we like the feeling.

• 18:11Neil deGrasse Tyson?

  Right. So if the feeling doesn't drive the dopamine, you're not even gonna have the thought.

• 18:17Speaker 03

  Right, exactly, and that's how GLP-1, in theory, can break down regulating that process, and that's why, you know, if we were only, if we only obeyed the homeostatic feeding triggers, most people would probably be normal weight, because we would eat to main.

• 18:32Neil deGrasse Tyson?

  Look like everybody in the 1970s.

• 18:33Chuck Nice?

  And I know Gary, I know you wanna get in here, but since you're on this right here, just right here, I wanna stay right here for one second, wouldn't it make sense then, that neurochemically, if we were to just deprive ourselves these kind of pleasure triggers, that our brain would naturally kind of go into a state where it doesn't care? Like, we wouldn't be seeking the rewards? So you cut out sugar for like, two weeks, right, and just stay off of it, like, your body will say, alright, F it, I don't want sugar anymore, you know?

• 19:07Neil deGrasse Tyson?

  Are you asking a question, or are you declaring?

• 19:09Chuck Nice?

  I'm asking, I'm asking.

• 19:10Speaker 03

  I think, I think it's not.

• 19:12Chuck Nice?

  That was my impression of my body, but I'm asking the question.

• 19:15Speaker 03

  Well, I think it's intuitive, but if you, if you ask anybody who's ever followed a fad diet, they can probably cut out all kinds of junk food and confectionery and alcohol for six weeks, two months, you know, they can go for a long time without that, and eventually they fall off the wagon, right? This, this kind of characterizes most people's experiences with dieting, which is why dieting never works, because as soon as you conceive the idea of a wagon, you're gonna fall off it, right? So.

• 19:42Neil deGrasse Tyson?

  So Chuck's answer is no?

• 19:44Speaker 03

  Probably no, there, there might be some kind of neurochemical mechanism that I'm not very, you know, that I don't fully understand, but experience tells me that that's not the case.

• 19:54Chuck Nice?

  Not gonna be the case, okay, cool.

• 20:10Gary O'Reilly?

  So Nick, we've got a neurochemical process here and it works on addiction and therefore dopamine. Are trials underway for this particular drug to work on dementia? And if so, what's the process in place?

• 20:23Speaker 03

  So most of these additional effects that we're reading about, supposedly this drug can reduce the risk of dementia and Alzheimer's and polycystic ovary syndrome and all of these other things. Most of that stuff is, this is where I turn into a grumpy old man, most of that stuff's reported by the mainstream media and as they tend to do, they misrepresent the mainstream science. So probably there is an indirect relationship between use of semaglutide and the overall risk for developing dementia in this case, but it's mediated by weight loss. So we know, for example, that people who have type 2 diabetes have a greater risk for developing dementia and other kinds of cognitive decline because of this systemic

• 21:05Speaker 03

  inflammation that occurs because of uncontrolled blood sugar levels, right? So if we help type 2 diabetics to better control their blood sugar, then they in turn reduce their risk of developing dementia and other types of cognitive dysfunction. So there is a very indirect link there, but it doesn't seem to be a direct mechanism. There's some evidence that maybe GLP-1 receptor agonists might help to improve cognition in some respects, but it's very early stage research and it's going to be a couple of years before we know anymore. So a lot of the time, if you can decrease somebody's body weight, help them to better control their blood sugar, then the risk for all sorts of things... A whole portfolio that comes in. Exactly.

• 21:48Chuck Nice?

  It seems to me, it seems to me like we're looking in the wrong area because from everything I hear about medically, inflammation is the worst thing that can happen to the body. It's the body's way of saying, "Look, I gotta get rid of some bad stuff," but the reaction to that is what is harmful. Why are we not looking for a way to just stop inflammation?

• 22:14Speaker 03

  Anti-inflammatory? I don't know. I don't know. Well, if you think about every major-

• 22:20Neil deGrasse Tyson?

  He's got to answer it quick before he blows a gasket.

• 22:22Speaker 03

  I think every major non-communicable disease exerts its kind of, its pathophysiology is due to inflammation.

• 22:31Chuck Nice?

  Yeah.

• 22:31Speaker 03

  So cardiovascular disease, for example, COPD, chronic obstructive pulmonary disease, cigarette smoking is so bad for you because it exerts systemic inflammation.

• 22:40Chuck Nice?

  Right.

• 22:40Speaker 03

  It's essentially all about, yeah, managing inflammation.

• 22:43Chuck Nice?

  Inflammation.

• 22:43Speaker 03

  And we mentioned at the start-

• 22:44Chuck Nice?

  Even high blood pressure, inflammation is the big problem.

• 22:48Speaker 03

  It seems to be inflammation. Even ultra-endurance exercise, which is an area that I've become interested in, is probably not super good for you in some respects because it induces this systemic inflammatory state. So yeah, trying to reduce inflammation, trying to reduce stress, physiological and psychological stress, seems to be a pretty important thing to do.

• 23:08Gary O'Reilly?

  So I have a double S question here. This, the sort of Ozempic drug that Groovyto Drugs gets released in, what, 2017? A, were they designed specifically to have these downstream effects? Or are we just slow to realize these benefits?

• 23:25Neil deGrasse Tyson?

  Well, there was something called COVID in between there, Gary. You know, just get real here, but Nick?

• 23:32Speaker 03

  Well, I try and answer your question. I think, I don't think we've been slow on the uptake to try and understand. We've known about GLP-1, so this is naturally produced GLP-1 that's produced from the intestine in response to- It's a hormone, isn't it? It's a peptide hormone that's produced naturally in the intestine, but, and we've known about the functions of GLP-1 for a long, long time, but the human-derived GLP-1 has a very, very short half-life. It's metabolized as a half-life of about 10 minutes. So it's secreted from the intestine and then it's very, very quickly metabolized. Only about 15, 20% of what's produced actually makes it into the blood.

• 24:12Neil deGrasse Tyson?

  Well, just, I have to insert here, because you borrowed the term "half-life" from physics. So in case people don't precisely know what "half-life" means, the half-life is always given with an interval of time, as Nick just did. So if the half-life is 10 minutes, after 10 minutes, half of that chemical remains. Another 10 minutes, half of that half remains. Another 10 minutes, half of that half. So it's two to that power of having. So if you do this three times, it's two times, two times, two is eight, one eighth of what's there. So rapidly, within an hour, this, I presume there's insignificant amounts in your, in your system, unless it continues to be produced.

• 24:52Speaker 03

  Right, and, and so, and I'm glad you did the math because there's no chance I would have been up to do that. But, but, but, and actually, that's a very interesting segue because how GLP-1 agonists were first discovered, it was actually discovered in the 1990s by a government-funded researcher called John Eng, E-N-G. And he was researching the various constituents of lizard venom. And so Chuck, what, how's your lizard knowledge?

• 25:15Chuck Nice?

  Let me tell you, I love lizards.

• 25:17Speaker 03

  Yeah?

• 25:17Chuck Nice?

  Oh, no, I'm sorry, that's lizzo.

• 25:23Speaker 03

  That's something different altogether.

• 25:25Neil deGrasse Tyson?

  Altogether different, yeah.

• 25:27Speaker 03

  Well, are you, are you familiar with the Hilo monster?

• 25:29Chuck Nice?

  Yes, I am very much.

• 25:30Neil deGrasse Tyson?

  We call it a Hilo monster, but yeah.

• 25:32Chuck Nice?

  Yeah, yeah.

• 25:33Speaker 03

  Yeah, okay. Well, so, so the, the, the Hilo monster has, is, as far as I'm aware, is North America's only venomous lizard.

• 25:41Chuck Nice?

  Lizard, yes.

• 25:42Speaker 03

  And, and so.

• 25:43Neil deGrasse Tyson?

  And, and it was the prehistoric creature of choice in 1950s movies, filmed close up, making you think it's big and bigger than the people running away from it. Because it's got that fourth tongue sticking out and it flops his legs and it's pretty scary. We've never seen one before and that was our, you know, before Jurassic Park and CGI dinosaurs, that was the best we could do.

• 26:07Speaker 03

  Beautiful. Well, his venom is also quite scary as well. And this, this character, John Eng, was researching the various constituents that made up the lizard venom. And he found that there was, there was a, a protein in, in the venom that had a very, very similar molecular structure to what we knew then to be GLP-1 produced in the human intestine. But whereas GLP-1, human GLP-1, had this very, very short half-life of 10 minutes or so, this lizard venom, this lizard venom protein, had a half-life of like five hours. So he immediately thought, well, if we could find a way to isolate this and synthesize it, maybe we could administer this, administer this to humans and help. But glucose control, fast forward a decade, over a decade, and the FDA finally approve

• 26:51Speaker 03

  a drug called Exenatide, which is based on this lizard venom protein.

• 26:56Neil deGrasse Tyson?

  Wow.

• 26:56Speaker 03

  And that was that, that was our first short-acting GLP-1 agonist. And since then, we've, we've developed uh, uh, GLP-1 agonists that have longer and longer half-lives, five hours, 10 hours, and then semaglutide has a, has a half-life of between five and seven days. So it's a long-acting GLP-1 agonist.

• 27:13Neil deGrasse Tyson?

  Wow.

• 27:14Speaker 03

  Which means it can exert its effect around the clock. Hence why it's so effective.

• 27:18Neil deGrasse Tyson?

  So the, the dose is a once-a-week dose, if I remember correctly.

• 27:21Speaker 03

  Right, it's a weekly dose, yeah. Exenatide was twice a day.

• 27:23Neil deGrasse Tyson?

  That's consistent with that information about the longer half-lives.

• 27:27Speaker 03

  Yeah, yeah, and Exenatide was twice a day, so people would have to jab themselves twice a day because of the half-life, whatever, five hours. And not only is it difficult, you know, it's difficult to get people to adhere to that kind of structure, uh, they also had to time the application around meals, much like they had to do with insulin, which is a drag for everybody, whereas semaglutide is a

• 27:47Neil deGrasse Tyson?

  It's not a drag if you would otherwise die, alright.

• 27:49Speaker 03

  Right.

• 27:49Neil deGrasse Tyson?

  Clear.

• 27:50Speaker 03

  It's preferable to, to death, correct.

• 27:53Neil deGrasse Tyson?

  Alright, so what, from everything we've been discussing, it does sound like a miracle drug. So, so where, where does your skepticism land in the presence of this drug relative to all the other drugs that have claimed to be miracle cures?

• 28:10Speaker 03

  Well, I, I've, I've gone back and forth on this, and I, and I've struggled with this quite a lot, actually, because as you, as you kind of alluded to, for the last more than a decade of my life, I've been very much an advocate, as an exercise scientist and a skeptic, of this idea that any health and wellness outcome that is worth achieving has to be worked, you have to work for it. You have to put in some time and some effort and some commitment.

• 28:35Neil deGrasse Tyson?

  Says the man who does triathlons, yes.

• 28:37Speaker 03

  Right, exactly, it takes time, you can't, you can't get these things over.

• 28:40Neil deGrasse Tyson?

  Dude, I wanna, I wanna be in, I wanna be in the shape that you're in, but I just, I don't wanna leave the couch.

• 28:45Chuck Nice?

  I, I was gonna say, Nick, we're only seeing you from, uh, like, uh, chest up, shoulders up, and, and, and we're like, yeah, this guy does, this guy does a lot of work.

• 28:54Neil deGrasse Tyson?

  My boy's two and a half percent body fat, for sure.

• 28:56Speaker 03

  Exactly, and it's like, it's a padded shirt.

• 28:59Neil deGrasse Tyson?

  Oh, oh, oh.

• 29:01Speaker 03

  I've got my, my, my, my storage of semaglutide, that's what you don't realize, is that

• 29:07Chuck Nice?

  You know, we actually were ribbing you about looking good, but we didn't let you finish telling us your convictions on Ozempic.

• 29:13Neil deGrasse Tyson?

  Yeah. Mr. Skeptic.

• 29:15Speaker 03

  Well, as an exercise scientist, as a skeptic, and for the longest time, I've always been of the opinion that to achieve any meaningful health and wellness change requires time and effort, right? And particularly, this obesity and being overweight is probably about as complex as a public health problem can be. Everybody wants simple solutions to complex problems.

• 29:35Neil deGrasse Tyson?

  You can't just run triathlons like I do and that'll lose your body fat. That's not gonna work.

• 29:40Speaker 03

  You can in some cases, if your exercise volume is so high that you're expending so much energy, then sometimes, you know, that will be enough to do it, but rarely is that the case. And so, but here we have a drug that is seemingly safe. No drugs are completely safe. There are side effects, which, you know, maybe we'll circle back to. But it seems to be apparently safe. One caveat to that is, we don't have studies on people that have been taking this drug for five or 10 years. So we don't know what the very long-term effects might be. It's definitely effective. You know, the average weight loss in a semaglutide trial is about 15% of body weight. So that's 30 pounds in a 200-pound individual.

• 30:19Neil deGrasse Tyson?

  I can use that. I can do that.

• 30:20Speaker 03

  It's definitely clinically meaningful. It will dramatically reduce somebody's risk of comorbidities. And, you know, I hate to say it, but we've been banging this drum about people improving their lifestyles and eating better and this kind of thing for decades. And the only thing that we've seen change is that obesity rates have gone up. And obesity rates have been trending upwards since the 70s. They're now going up exponentially.

• 30:42Neil deGrasse Tyson?

  Yeah, so Nick, it's an extraordinary phenomenon. And it could be just that the food industry has figured out how to make tasty, salty, fatty, calorie-dense foods that don't cost much money.

• 30:57Speaker 03

  And push them all day, every day, on every media outlet you can find. So here we go, Nick, let's flip this. If you've got somebody who is not clinically obese and is pretty good body weight for their size and all the rest of it, and you give them a semaglutide drug.

• 31:16Gary O'Reilly?

  The weight loss becomes a problem. Doesn't then it push other need for calories? And the kind of the addiction thing doesn't work as well? Does that happen?

• 31:25Neil deGrasse Tyson?

  No, if they weren't overeating to begin with, they weren't going through this dopamine cycle.

• 31:29Gary O'Reilly?

  Right?

• 31:30Neil deGrasse Tyson?

  Right? Am I right, Nick?

• 31:32Speaker 03

  Well, everyone, everyone has reward related behavior, particularly when it comes to food. Most people do.

• 31:37Gary O'Reilly?

  Scotch?

• 31:38Speaker 03

  Yeah, or Scotch, or alcohol, or psychoactive drugs, or gambling, or social media. Everyone has, everyone is constantly pushing that dopamine button in one way or another. And it just so happens that people who are very overweight seem to do it more often than not with food. But everyone, you know, if you didn't have any dopamine response, you'd have to be a robot, essentially. But, um, but anybody could potentially take these drugs and lose more weight. And this is, you know, Neil said at the beginning that he knows, you know, celebrities and things who have been taking Ozempic. And if you saw the Academy Awards this year, I didn't watch the whole thing, but Kimmel was the presenter. And in his opening.

• 32:17Neil deGrasse Tyson?

  He joked about it.

• 32:18Speaker 03

  He joked about it. He said, you know, I look around and I see all these slim, beautiful people and I can't help but wonder, is Ozempic for me? And, you know, it got a good laugh.

• 32:26Neil deGrasse Tyson?

  That is a good joke.

• 32:27Speaker 03

  But actually, cut, cut a little bit close to the bone, because a lot of people who can afford to pay $1,000, $2,000 a month are using the drug when they don't actually necessarily need it.

• 32:36Chuck Nice?

  I have a friend who's on it and he swears by it. And I said to him, but when you stop taking it, you're going to be fat again. And he was like, and so I just won't stop taking it.

• 32:49Speaker 03

  Right. And this is the other thing. And there's, I mean, they've done some really, really good studies. There was the step four study, which was published 2021 in the Journal of, in JAMA, Journal of the American Medical Association. And it was a really nicely executed study. They got a group of like 800 obese individuals and they put them all on semaglutide. They titrated up the dose for the first 20 weeks. So they started very, very low dose. Every week they increased the dosage until it was about 2.4 milligrams per week, which is the recommended dose. And in the first 20 weeks, everybody lost weight. And I think the average weight loss was about 10% of body mass, which is pretty good for 20 weeks work. They then split the group in half. Half the group continued on semaglutide for the rest of the trial for an extra year.

• 33:32Speaker 03

  The other group got placebo injections, right?

• 33:35Neil deGrasse Tyson?

  Oh.

• 33:35Speaker 03

  And you can probably guess what happened. The group that continued on semaglutide continued to lose weight. I think the average weight loss by the end of the trials between 15 and 20% body mass. The group on placebo regained pretty much all of the weight that they originally lost. But here's the kicker. Everyone in that study was receiving help with their diet. They were receiving lifestyle coaching and they were receiving monthly sessions with a psychotherapist to help them with the, you know, with the psychology of appetite suppression.

• 34:06Neil deGrasse Tyson?

  Which shows that psychotherapy is not working.

• 34:10Speaker 03

  Something in that trial wasn't working. But exactly as Chuck says, if somebody starts taking this drug, we better hope that there are no long-term side effects because people are going to have to take it for the rest of their lives if they want to retain their weight loss.

• 34:37Speaker 03

  Nick, where do we stand ethically with type 2 diabetes sufferers now being forced to wait for this drug that could be so beneficial for them? Because it's become the drug of choice for lots and lots of other people that actually don't have.

• 34:53Neil deGrasse Tyson?

  For some people, not to take them out of morbid obesity states, but others just to fit into the clothing that they didn't fit into, you know, a year ago. So is there enough of this to go around and to cover the people who really needed to save their life?

• 35:08Speaker 03

  The short answer is no. So the short answer is that the supply at the moment cannot meet the demand. And this is largely because, you know, it's been endorsed by a number of celebrities and, you know, and other types of famous people. It's trending on TikTok. A lot of fitness influencers are using it to, you know, help facilitate these dramatic body transformations. And whereas physicians are only supposed to be prescribing these things to patients, essentially, people who are clinically obese, so if their body mass index more than 30, or people with a BMI of 27 or more, who have an additional risk factor, right? Or somebody who's prediabetic or diabetic. These are all diagnosable conditions based on clinical criteria.

• 35:51Speaker 03

  But you can't stop a physician from prescribing it to somebody else who might ask for it. You can't stop people from getting it online, buying it overseas, buying it from friends. There is a way to get hold of this stuff. And as a result, as I said, supply cannot meet demand. And this is kind of real implications for a diabetic who has become dependent on Ozempic. Now, there are other options for type 2 diabetics. And Metformin, for example, for the longest time was the go-to treatment. And you can, of course, inject with insulin. But GLP-1 agonists, in terms of controlling blood sugar, are just as good, if not better, than insulin. And so if somebody's been used to taking Ozempic every single week, once a week,

• 36:35Speaker 03

  and then you ask them to switch to insulin because there isn't enough Ozempic to go around. There's a lot of trial. I don't know if you know somebody who's got type 2 diabetes or if you, you know. But there's a lot of trial and error that goes with the administration of insulin. You've got to figure out how much to use, when to inject it, to track your blood glucose concentration.

• 36:54Neil deGrasse Tyson?

  We've seen the ads where they have that sort of readable patch on their shoulder. And I'm thinking, wow, you got to monitor it every time, before you eat, after you eat, in between meals. And what happens after you have the banana, before you eat. And so, yeah, this is clearly.

• 37:08Speaker 03

  Yeah.

• 37:08Gary O'Reilly?

  So how soon before this market space becomes crowded with GLP-1 drugs? That will be for addiction, for dementia.

• 37:18Neil deGrasse Tyson?

  Do we need more demon monster to do?

• 37:19Speaker 03

  Yeah.

• 37:21Chuck Nice?

  And can we use monitor lizards instead?

• 37:24Gary O'Reilly?

  Good question.

• 37:25Speaker 03

  We definitely more of something. I mean, a lot of these synthetic forms are now, they are going to flood the market. You know, semaglutide is obviously highly sought after. There are a bunch of other GLP-1 agonists that are in development. There's one actually, tazepatide, which is, it's just finished phase three clinical trials. It will be approved by the FDA probably before the end of the year. And this is a dual-action GLP-1 GIP agonist. So I won't bother going into the mechanisms of GIP just for brevity. But they're basically synergistic together, and it's even more effective than semaglutide. So semaglutide in the 18-month clinical trials, average weight loss 15%. Tazepatide, average weight loss 20% or possibly even more.

• 38:07Speaker 03

  So this is just the beginning of GLP-1 receptor agonists. I think we're a long way off prescribing it for anything like addiction or any of these other indications.

• 38:18Neil deGrasse Tyson?

  If you know it affects the brain. In the hypothalamus or the hippocampus?

• 38:22Gary O'Reilly?

  Right.

• 38:22Neil deGrasse Tyson?

  Hypothalamus, yeah. You know, I was a big man on the hippocampus, you know.

• 38:26Gary O'Reilly?

  Oh, my God. Leave the funnies to Charles.

• 38:31Neil deGrasse Tyson?

  Okay. So.

• 38:34Gary O'Reilly?

  It's too early.

• 38:35Neil deGrasse Tyson?

  The hypothalamus, then that has nothing to do really with whether it's food or drugs or, or, you know. Alcohol. Alcohol, right, right.

• 38:45Gary O'Reilly?

  Social media, right.

• 38:46Neil deGrasse Tyson?

  It's just.

• 38:47Gary O'Reilly?

  There could be all sorts of addiction.

• 38:48Neil deGrasse Tyson?

  It disrupts the reward system.

• 38:49Gary O'Reilly?

  Yeah.

• 38:50Neil deGrasse Tyson?

  And that seems to be fundamental to so much of what can derail someone's life.

• 38:55Gary O'Reilly?

  Wow, sure.

• 38:56Speaker 03

  Yeah, and you're absolutely right. The implications of that could be huge, but at the moment, a- as I said, this is only being studied experimentally in, in mice and rats. And so we don't know the safety profile of administering in those kinds of doses. We don't know exactly what dose would be needed to treat addiction in the long term.

• 39:13Neil deGrasse Tyson?

  I have a lab rat question. So they, you know, an old mouse is three years old, right? So if they go through multiple generations, or rather, um, what am I trying to say? You, there are animals that don't live as long as we do. So aren't you allowed to scale the long-term effects into their short lifetime to get a sense of it, what the long-term effects might be in us? At least get a first hint at it?

• 39:39Speaker 03

  You can definitely get a hint at it, but, but one thing that, that scientists and physicians warn against is giving somebody a small dose over a 10-year period, it, it doesn't necessarily induce the same results as giving somebody a high dose over a very short period. It doesn't always scale very, very well.

• 39:56Neil deGrasse Tyson?

  Okay.

• 39:56Speaker 03

  So we, we can't, we can't wait to get these data in real time because then we'd have to wait five and 10 years.

• 40:01Neil deGrasse Tyson?

  Had to wait 10 years.

• 40:02Speaker 03

  And, and people are gonna, you know, become very unwell in that.

• 40:05Neil deGrasse Tyson?

  Everybody knows she said these data, because data are plural.

• 40:09Speaker 03

  It's a plural now.

• 40:09Neil deGrasse Tyson?

  And a singular data is a datum, just so you know. Ooh.

• 40:13Gary O'Reilly?

  Ooh.

• 40:13Neil deGrasse Tyson?

  Our boy.

• 40:14Gary O'Reilly?

  So here, Nick, thinking about this, there is going to have to be off-label legislation, right? And the control thereof, of prescription of off-label drugs. But who wins? The clinical innovation or the legislation? Because if you, if you just crush innovation within a clinical environment, what's the incentive to go forward if you're still waiting that a period of time?

• 40:39Speaker 03

  This is a very hotly contested and highly divisive issue because on the one hand, you've got scientists and physicians who very much feel that the FDA, for example, so the FDA are the regulatory body for all of the new drugs that come onto the market, and the FDA are the gatekeepers for which drugs can be promoted commercially by pharmaceutical companies. And some people think that they are overly bureaucratic and that in doing so, they prevent drugs or delay drugs getting on the market that could be helping people, right? So that's kind of, and these people will always put forward these, you know, hundreds of examples where patients are waiting for drugs to get approval and they

• 41:22Speaker 03

  need these drugs, and then the drugs are finally approved, but it comes too late for these events.

• 41:26Neil deGrasse Tyson?

  Of course, that was the entire theme of the Dallas Buyers Club.

• 41:28Speaker 03

  Oh, yeah, that's right.

• 41:30Neil deGrasse Tyson?

  As the storyline. And of course, and there was emergency, some, there's some regulatory emergency bypass that was enabled for COVID vaccines, is that correct?

• 41:43Speaker 03

  Right, yeah, yeah. So they were, so the actual approval process was expedited. We should, you know, hasten to add that these mRNA vaccines, for example, have been in development for a decade or so.

• 41:54Neil deGrasse Tyson?

  A decade, yes.

• 41:55Speaker 03

  But the actual approval process was expedited for that very reason because, you know, hundreds of thousands, millions of people around the world are dying already. So you can't wait two or three years that you would do for the normal process. And it obviously turned out to be the right choice. But at the other end of the extreme, you have people arguing the opposite, that the FDA are, they need to be more bureaucratic, they need to be more conservative, because history is littered with instances where the FDA were premature to approve a drug that then turned out to have really nasty side effects.

• 42:27Neil deGrasse Tyson?

  I hear less of that than the other, but I believe you that they're out there, that they want it to be even more conservative.

• 42:33Speaker 03

  Fen-phen! Yes, fen-phen's a great example. So it was, you know, the 1930s, 40s, 50s, the main drug that we used to treat obesity, the royal we, of course, was amphetamine. Because amphetamine is a very powerful stimulant, as you know, it increases metabolic rate, increases sympathetic drive, helps people burn more calories, which is great. It was moderately successful at helping people lose weight. But it was obviously highly addictive because amphetamine is addictive and it caused all sorts of heart problems and heart complications.

• 43:06Neil deGrasse Tyson?

  Right.

• 43:07Speaker 03

  Then fentanyl was approved in the late 1960s, I think. And fentanyl is a less powerful stimulant, but it still kind of exerts stimulant-like effects. And again, it was moderately successful at helping people to lose weight by working as an appetite suppressant. Fluoramine was approved shortly after that. And then some bright spark thought to themselves, well, if we combine these two drugs together, we get even more potent effect. The thing was featured, they eventually did approve it as Redux, which was featured on the cover of Time Magazine. There were 18 million prescriptions for the drug the following year.

• 43:46Speaker 03

  100 Americans died because of heart problems and 20% of the people who received a prescription for Fen-Phen or Redux had to have heart surgery to correct damaged heart valves.

• 43:59Neil deGrasse Tyson?

  Wow.

• 44:00Speaker 03

  So that's an example of not only a drug that was being prescribed off-label when it shouldn't have been, but the FDA being under so much pressure to try and tackle this growing obesity epidemic or this increases in population body weight, that they sort of jumped the gun on the safety profile.

• 44:17Neil deGrasse Tyson?

  How often do you hear about Americans having to go to Mexico or to France to get a drug that's not yet approved by the FDA?

• 44:24Speaker 03

  Right.

• 44:25Neil deGrasse Tyson?

  We hear that a lot. But on the other side of that, it may even be worse in the full spectrum of public health.

• 44:32Gary O'Reilly?

  So what's the percentage, Nick, of off-label drugs in terms of doctors' prescription?

• 44:38Speaker 03

  So just for the listeners who aren't sure, off-label means it's a drug that has been FDA-approved, but then a physician has decided to write a prescription

• 44:47Neil deGrasse Tyson?

  For something else.

• 44:48Speaker 03

  For some other indication or in a different dose or in a population for which it hasn't already been approved, okay? And it's probably about between 20 and 30% of all prescriptions are for off-label drugs. So it's very common. It is not illegal. It's widely practiced in the States and around the world. But I think it probably needs some better regulation because the FDA, of course, they regulate the availability of new drugs. They don't regulate medical practice. So the FDA are very much hands off when it comes to off label. So ivermectin can be prescribed for COVID even though it's an antiparasitic? So the general criteria for the, or the recommendations for a physician to prescribe

• 45:33Speaker 03

  off label, the drug has to be supported by scientific evidence and/or sound scientific evidence. The physician has to lean heavily on their medical experience. And of course, the third thing goes without saying that the physician has to have the patient's best interests at heart. The problem with that is-

• 45:51Neil deGrasse Tyson?

  First do no harm. That's what that is.

• 45:52Speaker 03

  Right, exactly. First do no harm. A prima non necera. But the problem with that is that what I consider to be sound scientific evidence might be very, very different to what somebody else considers to be sound scientific evidence. And if a physician leans heavily on their medical experience, well, what if they don't have much experience? What if their experience pales into comparison, you know, relative to their, you know, somebody-

• 46:18Neil deGrasse Tyson?

  That's what the internet is for, so they can put up a YouTube video. We've seen-

• 46:22Speaker 03

  Right, exactly. You can just go and watch YouTube. We know, for example, on the ivermectin case, you know, I read a study that was published earlier this year that found that conservative physicians were more likely to prescribe ivermectin and hydroxychloroquine for treating COVID-19. And the main driver for that was cable news.

• 46:41Chuck Nice?

  Cable news. Right. You know, I will say this, though. I took ivermectin when I had COVID and my intestinal worms were cured.

• 46:50Speaker 03

  You cured them straight away.

• 46:51Chuck Nice?

  COVID. I still kept the worms. They just didn't have COVID.

• 46:55Neil deGrasse Tyson?

  And you still live in the stable with the other horses.

• 46:57Chuck Nice?

  And I still live-

• 46:59Speaker 03

  Yeah.

• 47:00Chuck Nice?

  By the way, I can't stop eating hay now.

• 47:03Neil deGrasse Tyson?

  Guys, we gotta end it. We gotta land this plane. Nick, this has been a delight to have you on yet a second time. I know it's not gonna be our last time because you are a trove of information and you can hear how curious we are. You know how curious our fanbase would be as well. So thanks for this second appearance on StarTalk.

• 47:22Speaker 03

  Thank you. It's been great to see you guys again. So thanks for having me.

• 47:24Neil deGrasse Tyson?

  All right. Chuck and Gary.

• 47:27Chuck Nice?

  Always a pleasure.

• 47:28Speaker 03

  Pleasure, Neil.

• 47:29Neil deGrasse Tyson?

  All right. This has been Neil deGrasse Tyson's special edition. This one on quick fixes. Deal or not?

• 47:37Neil deGrasse Tyson?

  Until next time, keep looking up.