Weight Loss Drugs & GLP-1 Science | Neil deGrasse Tyson & Nick Tiller

[00:00:00]coming up on Star Talk Our Guest is Dr Nick tiller he's 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 [Music] 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 I'm good now all right to be on former Soccer Pro and sports commentator professionally and we we they lend him to us for this purpose gives us street cred anytime we think about human physiology and sports of course we got Chuck Nice Chuck how you doing man hey buddy what's happening long time co-host and your comedian and actor all right so Gary you and your producers like think this stuff up so clue me in what today is about um in a previous episode we explored Quick Fix Solutions in the health and wellness industry yes fixes everything boom there you go buddy and uh we're not we're not talking tape and we're out quick fix guys for everything in life well okay that in 420. um so this show basically was a must do because right now the quickest fixes in town are weight loss drugs uh ozempic and would go be 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 he's been on it before so Neil introduce Our Guest please oh took Dr Nick tiller who's it's the second time on start talking a returning Champion returning Champion a repeat offender you could say oh there you go and I I discovered you I mean not discovered you but for myself I I realized you existed upon seeing the cover of your book The Skeptics guy to sports science because 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 you had him at skeptic yeah the moment he saw a skeptical yeah I used that word very very precisely I knew what I was doing when I when I titled it that yeah you've got it so you you have a PhD in respiratory functions of human physiology your 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 colonist also for skeptical Inquirer magazine my single favorite magazine in the world let the record show yes everything is indeed 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 start talk it's great to see you guys again thanks for having me back 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 can you imagine oh so could you imagine if it was with Govi and they started with wee-wee it wouldn't be as good it wouldn't be as good okay 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 oh and I'm like really it's good marketing huh I was like damn that you were watching too much TV girl I expected better for her as the daughter of a comedian just thought I'd put it out there oh yeah maybe I'm not that good of a comedian we've heard a lot about this I knew it had some uh relevance to to uh 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 well I guess ozempic was FDA approved so any drug that become that comes onto the market has to be approved by the Food Drug Administration uh 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 the insulin their insulin resistance 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 and glucose is synonymous in that example with energy driving your body needs correct 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 it's one of that that family of osis right the sucrose fructose glucose so they're all sugars right yeah they're all sugars glucose is the simplest form of sugar there's a single molecule fructose is another one that's a single molecule sucrose what we call table sugar is is a disaccharide so it's it's glucose and fructose bound together but it 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 the blood sugar because of the reason that I just mentioned that they're either not producing enough insulin diet that's type one okay type two diabetes they're producing it but it's not it's not potent enough it's not exerting its effect your 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 body will try to maintain if my glucose is too level yeah you won't you don't know because you're unconscious right well yeah whoever's in the room with you will know because you'll be lying horizontal on the floor okay so your body will do whatever it can to maintain your blood sugar levels within this kind of narrow normal dysm static range so this drug that uh that we call the zenpick it's called it's called a glp-1 Agonist and glp1 is glucagon-like peptide one as a very important role in the body that when we take in some food particularly if the food contains fats and sugars or stimulate the release of glp-1 which acts on the pancreas which then stimulate which then releases insulin is there a term for the drug is it I mean we've been calling them GOP ones so the drug itself is called semaglotide 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 could 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 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 and then in 2021 the FDA reapproved semacletide under a different brand name wegovi specifically to help people to lose weight but it works via the same kind of mechanism it seems to me there's an interesting back door 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 that's correct as long as your doses are within the range of the originally intended dose it doesn't have to be tested that's why everybody loves the little blue pill you're right well and that was that's an interesting one actually because 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 sildenafil citrate because I can't remember the drug names but sedentical citrate was discovered because researchers were looking at ways to lower blood pressure right 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 that's right it's gone full circle it's gone full circle so what is it about carrying extra weight specifically subcutaneous belly fat that leads to diabetes what is that Association I never knew the answer for that myself so yeah what is going on there 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 viscerin so and Surround your pancreas and your liver and so forth so because this fat is more metabolically active it is it has a much more a much closer association with disrupted a lot of 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 women in general tend to store more of their body fat around their hips and bums I'm so lucky well and 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 so that means men are more prone to type 2 diabetes than women based on this analysis men who have greater uh waist to hip ratios yeah right right so small truck we need a Sir Mix-A-Lot to do song about men's belly fat that's right I like big guts in the camera all right so Nick um when patient's been treated the type 2 diabetes with the I call it semi-glutide but some magnetite it's a tomato it's a tomato whatever that's because you're English I know sorry uh 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 is there enough clinical evidence to back up this Downstream of labeling of this stroke as uh as as another use or is it you know was it enough of you know what doc or 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 in another way yeah so the only similarities between the two approval processes is that cementide semiglutid has already gone through the phase one and two trials which are essentially about uh making sure that 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 some aglotide for weight loss because it is a slightly uh I guess you could could say it's a slightly different mechanism so so you have glp1 it has a bunch of different effects on the body wherever there's a concentration of glp-1 receptors then glp1 is going to exert 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 up regulate the the secretion of insulin and it helps the beta cells of the pancreas which actually does the secreting of insulin to proliferate and it sort of they increase in number so it can actually help to treat turkey diabetes in that way but we know that glp1 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're taking food you swallow the food down into the stomach it comes into into contact with these uh different lipases and different enzymes to break down the food and hydrochloric acid and it turns the food into a into a mushy sludge and it then empties into the small intestine and glp1 actually 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 secretes 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's helped to suppress appetite in that way but there's there's one other mechanism that's really important that we have to mention and that glp-1 also act on receptors in the brain so yeah epithalamus is the is the body's kind of appetite control center and by stimulating glp-1 receptors in a hypothalamus then we can actually reduce appetite increase feelings of satiety and people want to eat less 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 suppressing urges or emerges very good thank you is that where the brain part of this comes in it's probably not just correlation it probably is causation the reason that I say probably is because this all started because patients who are prescribed some acletide for one reason or another but coming back to their doctor saying it's 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 have also been suppressed yeah so so then we started to look at this under control 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 uh that glp-1 acts to down regulate dopamine Transmission in the brain and dopamine as we know has an entire episode on dopamine so people want to look into our archives absolutely and and when we 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 and uh reward seeking mechanisms and by down regulating that pathway then glp-1 can in theory help to to improve impulse control and decrease reward seeking behavior and that would be for whatever stimulates dopamine so 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 notice not only did they eat less but they were deriving less enjoyment from the food this isn't it worthy it was a double effect it's like not only am I not really hungry I don't even want and so some of them were worried that it was subtracting away from them this this big part of their social life going out enjoying fine foodie type things prepared by by high profile chefs you call this a Michelin star meal you didn't need a tandemon's epic rating of this of the meal right it's one of those repercussions that you don't even think about but but yeah I guess we have to frame this in the context that there are there are two types of feedings there's what we call homeostatic feeding and then this hedonic or hedonic feeding and they kind of they're self-explanatory but homeostatic feeling is when we eat because we you know we haven't had enough calories you've got to survive right to live not living to eat if you go out and do a you know a hard training session or you haven't eaten for a number of hours then you're going to have a negative calorie def you're gonna have a calorie deficit so your body's going to tell you to go and eat more and that's almost homeostatic homeostatic feeding exactly just in an effort to maintain normal dynamic equilibrium by the way way you were that sounds like we're zoo animals okay it's your feeding time in a way yeah let's not talk about that thread and so and so hedonic feeding is literally is uh is is chasing that reward seeking Behavior 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 yeah dessert yeah yeah we don't need the calories but we like the feeling right so if the feeling doesn't drive the dopamine you're not even going to have the thought right exactly and and that's how this 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 right most people would probably be normal weight because right we would eat to it looked like everybody in the 1970s and I know Carrie I know you want to get in here but it's just showing this right here just right here I want to stay right here for one second wouldn't it make sense then that neurochemically if we were to just deprive ourselves these kind of um 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 all right effort I don't want sugar anymore you know 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 is 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 Charlie's answer is no probably no that there might be some kind of neurochemical mechanism that I'm not very you know that I don't fully understand but um experience tells me that that's not the case hey Neil happy sweet 16. what this is your 16th book coming out the one that we started working on together two years ago this yeah yeah well thank you yes it's my 16th book practically forgot about because I've been very busy and I guess it's coming out in a month well it's my first book so oh sorry we gotta do something sir so I should be more excited that okay absolutely but I think this is your best friend so Nick we've got a neurochemical process here and it works on addiction and therefore dopamine our trials underway for this particular drug to work on dementia and if so what's the process in play so most of these additional effects that we're reading about so you know but 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 you know as they tend to do they misrepresent the mainstream science so probably there isn't there is an indirect relationship between use of some acletide 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 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 they they in turn reduce their risk of developing uh 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 grp1 receptor agonists might help to improve cognition in in some respects but it's very early stage research and it's going to be a couple of years before you 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 their risk for all sorts of things portfolio that comes in right exactly it seems to me like we're looking in the wrong wrong area because from what from everything I hear about medically inflammation is the worst thing that can happen to the body right 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 foreign exerts its kind of its pathophysiology is is due to inflammation yeah so cardiovascular disease for example uh COPD chronic obstructive pulmonary disease cigarette smoking is so bad for you because it exerts systemic inflammation this is essentially all about yeah managing inflammation and we've mentioned even high blood pressure inflammation is the big problem it seems to be inflammation even Ultra endurance exercise which is an area that I've become interested in it's probably not super good for you in in some respects because it it induces this systemic inflammatory state so yeah trying to reduce inflammation trying to induce stress uh physiological and psychological stress seems to be a pretty important thing to do so I have a double s question here this the sort of a zympic drug that group of 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 well there was something called covet in between there yeah you know just let's get real here but Nick yes well I should to 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 it's a hormone isn't it it's a hot 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 has 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 percent of what's produced actually makes it into the blood which is 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 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 2 to that power of having so if you do this three times it's two times two times two is eight you have one eighth of what's there so rapidly within an hour this is I presume there's insignificant amounts in your in your system unless it continues to be produced right and and so and I'm glad you did the math because there's no chance I would have been able to do that but uh but but but and actually that's a very interesting segue because how glp-1 agonists were first discovered was actually discovered in the 1990s by a government-funded research called John Eng and he was researching the various constituents of lizard Venom and so Chuck what how's your lizard knowledge and let me tell you I love lizards yeah oh no I'm sorry that's lizzo there's become something different all together all together well are you are you familiar with the Hilo monster yes very much we call it another monster but yeah yeah yeah okay well so so the the uh the killer monster has is as far as I'm aware is North America's only venomous yes lizard yes and and so 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 sticking out and it flops his legs and it's pretty scary if you've never seen one before and that was our you know before Jurassic Park and CGI dinosaurs that was the best we could do 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 the lizard Venom and he found that there was uh 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 producing the human intestine but whereas glp-1 human glp1 had this very very short half-life of 10 minutes or so this lizard Venom this lizard Venom protein had a half over 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 with blood glucose control fast forward a decade over a decade and the FDA finally approve a drug called examine a tide which is based on this lizard Venom protein and that was that that was our first short acting glp-1 Agonist and since then we've developed uh uh geopy one agonists that have longer and longer half-lives five hours ten hours and then some magnetite has a has a half-life of between five and seven days so it's a long-acting deal which means it can exert its effect around the clock so the the dose is a once a week dose if I remember correct right it's a weekly dose yeah twice a day that's consistent with that information yeah yeah an xenotype was twice a day so people would have to jab themselves twice a day because of the half-life whatever five towers and not only is there 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 magnified it's not a drag if you would Otherwise Die all right it's preferable to death correct I thought 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 well I I've I've gone back and forth on this and I've struggled with this quite a lot actually because as you as you kind of allude 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 what you have to work for it you have to you have to put in some time and some effort and some commitment so as the manager does triathlons yes right exactly it takes time you can't we can't get these things I want to be in the shape that you're in but I just I don't want to leave the couch I was going to say Nick we're only seeing you from uh like uh chest up shoulders up and and we're like yeah two and a half percent body fat exactly sure it's a padded sure and my storage of some agletide that's what you don't realize we actually were ribbing you about looking good but we didn't let you finish telling us your convictions on ozempic yeah Mr skeptic well as an exercise scientist as a skeptic and for for the longest time I've always 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 and being overweight is probably about as complex as a public health problem can be everybody wants Simple Solutions to complex problems and you can't just think run triathlons like I do and that'll lose your body fat that's that's not gonna work you comment you can in some cases if your exercise volume is so high that you're expending so much energy then sometimes you know that 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 maybe we'll Circle back to but uh it seems to be apparently safe what one caveat to that is we don't have studies on people that have been taking this drug for five or ten years so we don't know what the very long long term effects might be um it's definitely effective you know the average weight loss in a somaglotide trial is about 15 of body weight so that's 30 pounds in a 200 pound individual I can use that I could do that definitely clinically meaningful it will dramatically reduce somebody's risk of comorbidities and you know I I hate to say it but we've been banging this drum about people improving their Lifestyles and eating better in this kind of thing for decades and the only thing that we've seen change is that obesity rates have gone up oh yeah and obesity rates have been training upwards since the 70s they're now going up exponentially yes so I so Nick it's a it's an extraordinary phenomenon and it could be just that the food industry has figured out how to make tasty salty fatty uh uh calorie dense foods that don't cost much money 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 uh drug 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 no if they weren't overeating to begin with they were they weren't going through this dopamine cycle right right am I right Nick well everyone everyone has reward related Behavior particularly when it comes to food most people do so if you don't 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 could potentially take these drugs and lose more weight and this is what you know Neil said at the beginning that he knows he knows you know celebrities and things who have been taking a zenpick and I don't know if you saw the Academy Awards this year I didn't watch the whole thing but uh Kimmel was the was the presenter and in in his opening monologue 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 it actually cut cut a little bit close to the Bone because a lot of people who can afford to pay one thousand two thousand dollars a month are using the drug when they don't actually necessarily need it I have a friend who's on it and uh 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 right 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 execute study they've got a group of like 800 obese individuals and they put them all on some agletide 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 percent of body mass which is pretty good for 20 weeks work they then split the group in half half the group continued on some agletide for the rest of the trial for it for an extra year the other group got Placebo injections right and you you can probably guess what happened the group that continued on some acletide continued to lose weight and I think the average weight loss by the end of the trials between 15 and 20 body mass the Groupon 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 with a psychotherapist to help them with the you know with the psychology of appetite suppression is is it's probably it's not working something in that trial wasn't working 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 Where Do We Stand ethically when type 2 diabetes suffers 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 don't have 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 the people who really need it to save their life the sure answer is no so the short answer is that there's a puppy Supply at the moment cannot meet the demand and this is largely because you know it's been endorsed by a number of of celebrities and you know and other types of famous people that's trending on Tick Tock 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 to patients essentially people who are clinically obese so they add 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 pre-diabetic or diabetic these are all diagnosable conditions based on clinical criteria but you 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 this kind of real implications for a diabetic who has become dependent on ozempic now there are there are other options for type 2 diabetes type 2 diabetics and you know metformin for example for the longest time was the the was the go-to treatment and you can of course inject with insulin but uh 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 and then you ask them to switch to insulin because there isn't enough exemptic 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've you know but there's a lot of trial and error that goes with the administration of of insulin yeah you've got to figure out how much to use when to inject it to track your blood glucose constantly ads where they have that sort of readable patch on their shoulder and I'm thinking wow you're going 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 yeah how how soon before this Market space becomes crowded with GOP one drugs that will be for addiction foreign we use monitor lizards instead good question we definitely more of something I mean a lot of these synthetic forms are now they are going to flood the market you know some magnetite is is obviously a highly sought after there are a bunch of other glp-1 I guess uh that are in development there's a there's one actually to zapatide which is in 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 it's I won't bother going into the mechanisms of Gip just for barity but it uh they're basically synergistic together and it's even more effective than some agletide so some magnetite in the 18-month clinical trials average weight loss 15 to zepatite average weight loss 20 or possibly even more so so this is just the beginning of glp-1 receptagonists yeah um I think we're a long way off prescribing it for anything like addiction or uh any of these these other indications no it affects the brain in hypothalamus or the okay [Music] then that has nothing to do really with whether food or drugs or or you know alcohol or alcohol right it's just the reward system yeah that seems to be fundamental to so much of what can derail someone's life Wow sure yeah and you're absolutely right the implications of that could be huge but at the moment 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 um 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 you can definitely get a hint at it but but one thing that that uh scientists and Physicians uh warn against is giving somebody a small dose over 10-year period 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 okay 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 ten ten years and and people are gonna you know become very unwell in that time everybody notice he said these data because data are plural it's a plural noun and if a singular data is a datum just so you know right so hey Mick thinking about this there's 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 an incentive to go forward if you're still waiting that a period of time yeah this is a very uh hotly contested and highly divisive issue because on the one hand you've got you've got scientists and Physicians who very much feel that that the FDA for example so the FDA uh the regulatory body for all of the new drugs that 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 that's kind of and and these people will always put forward these you know hundreds of examples where patients are waiting for drugs to get approval and they need these drugs and then the drugs are finally approved but it comes too late for these questions oh yeah that's right at the storyline and of course uh and there was emergency some there's some regulatory emergency bypass that was enabled for coveted vaccines is that correct right right yeah yeah so 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 but the actual approval process was expedited for that very reason because you know hundreds of thousands of millions of people around the world were 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 they need to be more conservative because history is littered with with instances where the FDA were premature to approve a drug that then turned out to have really nasty side effects I heard left with that than the other but I I believe you that they're out there that they wanted to be even more conservative yes Ben Fan's a great example so so it was you know the 1930s 40s 50s a bit the main drug that we use to treat obesity the Royal way of course was amphetamine because amphetamine is a very powerful stimulant as you know it increases metabolic rate increases sympathetic dry 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 isn't it is addictive and it caused all sorts of heart problems and heart complications then Phentermine was approved in the late 1960s I think and Phentermine is a a less powerful stimulant but it's 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 uh fluoramine was was approved um shortly after that and then some bright spark thought thought to themselves well if we combine these drugs together we get an even more potent effect the the thing was um featured they they eventually did approve it as Redux which was a which was featured on the cover of Time Magazine there were 18 million prescriptions for the drug the following year a hundred Americans died because of heart problems and 20 of the people who received a prescription for fenfen or Redux had to have heart surgery to correct damaged heart valves so that's an example of not only will 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 you know obesity epidemic or this increases in population body weight that they sort of jumped the gun on the safety profile so understandably now how often you hear about Americans having to go to Mexico or to France to get a drug that's not yet approved by the FDA right we hear that a lot but on the yeah on the other side of that uh may even be worse in the in the in the full spectrum of Public Health what's the percentage Nick of off-label drugs in terms of doctor's prescription so 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 to write a prescription uh for something else for some other indication or in a different dose or in a population for which you hasn't already been approved okay and the it's probably about between 20 and 30 of all prescriptions are for off-labeled drugs so it's very common it is not illegal it's uh widely practiced in the states and around the world um 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 leap so either mechan can be prescribed for covid even though it's an anti-parasitic right and exactly so the general criteria for the or the recommendations for a physician to prescribe off-label they 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 the patient's best interests at heart the problem with that is right exactly first do not harm a premium 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 scientific evidence and if a physician leans heavily on their medical experience well what if they don't have much experience what if they their experience Pals into comparison you know relative to their uh you know somebody internet is for so they can put up a YouTube video we've seen 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 hydro hydroxychloroquine for treating covid-19 and the the main driver for that was cable news cable news right you know I will say this though I took ibramectin when I had covid and my uh my intestinal worms were cured drugs straight away I still kept the worms they just didn't have covet and you still haven't seen benefits with the other horses right yeah actually I can't stop eating anything guys you gotta end it we gotta 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 were a trove of information and you can hear how curious we are you know how curious our our fan base would be as well so thanks for uh this second appearance on Star talk thank you it's been great to see you guys again so uh thanks for having me all right uh Chuck and and Gary's a pleasure all right pleasure nail all right the other gas station special edition this one on quick fixes real or not until next time keep looking up [Music]