Okay, so I don't forget to help you. Um, well, first of all, I just wondered if you had any questions for me about like what I'm doing. But um,
I mean, I guess that's a good start. I assume you, actually, that's probably a good start. What is what am I being interviewed for?
Yeah. So we're just a daily news podcast, we have longer segments. So this is one of those longer segments. So it's not like a straight q&a where like, you gotta get your questions or answers right the first time, you know, I'm kidding. Kind of go through it and make it make it. So
this is, this is a podcast. This is not, this is not a written interview. Okay. You see, I'm saying, Look, I could have shown up in my gym jabs, so this is alright. Yeah.
Um, yeah. So if you do get where you're like, Oh, I could say that better, you know, or something like that. You totally can, and it'll be easy to cut together. You know, whatever. I pulled up my questions, but then I realized I had questions. The other ones pulled up. So one second.
Food Do you don't mind me drinking coffee where we do this?
Oh, no. I will also be drinking coffee. Yes. Where are you based? Procrastination mug? North Carolina.
North Carolina. Okay.
Yeah. It's very fun. Where are you coming to New York?
Do you know it's a very good question. I have got a state and I'm doing another podcast and I thought it was gonna be via zoom. Like, like like this. But clearly these people have thought that they told me Zoom. Zoom. We need you in studio in New York. What? So? I'm going to I'm going to New York to do and to do an interview in studio.
Yeah, who's it with?
Well, it's a biotech company, drug company, is funding it. They're putting together sort of a, a Podcast Series C series, six, six parts, but they're clearly throwing real money at this. And so they've got four, four or five, four or five American scientists. I've originally American. But anyway, scientists and and me, which they've chosen to fly in from, from the UK. And they've got to do it's a podcast, but also with the obviously, filmed as well. I don't know what the I don't know what I'm going to do with so so hopefully nothing bad. All right.
Yeah, hopefully nothing bad. that would that would be good. Yeah. Wow. All right. Well, that'll be fun. Um, okay, I finally got my questions. So, yeah, so I'm kind of doing this on like, the growing popularity of these and you know, the history and what I said the email all that jazz. So can you tell me a little bit about how the UK is viewing obesity as a disease versus non disease? Because it sounds different?
I mean, it is that is an it's an interesting question. I don't we have not we as certainly our National Health Service has not actually put it out that assess obesity is definitely a disease. I think there is still controversy. And there's still discussion that's actually going on at the moment, but I think within the field, and we are a government funded as the equivalent of the equivalent of the NIH, the MRC funded obesity unit, in which we are trying to tackle obesity. And so clearly, the powers that be silly the funding bodies consider obesity to be a disease. And so So, so that, so I certainly consider obesity to be a disease.
Gotcha. Okay, that makes way more sense, is how they're eating a little bit about it. And I was like, sounds like you're doing the same thing. As the US. You're just not saying, yeah, no,
no, exactly. So what we haven't done is whether or not it's the policymakers, you know, these things are often done by policymakers rather than actually asking the people working on the issue. So now it's officially not like a disease bang out there. But like all of us working on the field, I'm considered a disease. It's funded like it's a disease. We're trying to treat it as a as a problem.
Yeah, okay. That makes sense. That's, that's cool. So how do you think these these newer weight loss drugs are impacting that that work?
We will I do read I don't want to engage in hyperbole necessarily. But I really do think that it is these are remarkable drugs. I do think we are at a an inflection point in in, you know, the history of obesity research, so to speak, in being able to treat obesity and I say the word treat as opposed to prevent because these drugs are not going to prevent obesity. So that's another discussion for another day. But as far as treating obesity, I think what is clear is that there are going to be a large number of people of humans who are going to be responsive to these drugs and who will be treated by by by these drugs. I I don't think there are silver bullet. I don't think they're the be all and end all. I think at the most severe end of obesity, you know, 600 pounds, you know, the stuff that you see on TV and someone has to be craned out of the of the house. I still think that bariatric surgery, so, replumbing, the replumbing, our gastrointestinal tract, I think that's still going to be the way to go. Because it's quick, and it's permanent, these drugs are not permanent, meaning that you got to keep taking them. And then I think there's going to be a stage where I could probably stand to lose five or 10 pounds, right. And no one is going to, certainly we have a national health care system. So our national health care system is not going to pay for me to get as epic or whatever, right. And so I probably sit within the realms of behavioral change, what whatever you want to take changing my diet, exercising more, that kind of thing. But really, there is a huge gap in between, between the severe severe obesity that will undergo really quite a major permanent surgery, and for whom behavioral change is just not working. Okay. And these new class of drugs full fit in this in this space.
Okay, that makes sense. So, tell me a little bit about that history of treating obesity or trying to?
Well, so I, I'll go a little bit before the history. So it's one of these things where, when we first started studying obesity, I mean, I hope I'm not there at all, but I was there near near the beginning, certainly when when we will be getting to identify molecules, which, when mutated, resulted in severe obesity. That's how this whole this whole thing started in terms of finding in terms of finding pathways. And in when we first started, and we were looking at obesity, you could ask well, what is? Where do you think the cause of obesity is? Is it in the stomach? Is it because of fat? Is it because of our eyes, liking more food, whatever, okay. But what happened was, as we were moving through and looking at naturally occurring mutations in human human beings causing severe obesity, and then, you know, trying to model and functionally look at this in mice, what we began to realize is that the genetics of bodyweight obesity is just one end of the spectrum is the genetics of how our brain controls food intake. And so we needed to sort of work our way through the process of finding out that well hang on a second, I think we need to tackle the brain, if we're going to tackle obesity, there were there was a lot of other drugs that were trying to increase energy expenditure. Safely. Those have come those have gone, there's been questionable success, some dangerous, then there was trying to stop us from absorbing as much food meaning that, you know, allow us to eat and in effect, we could eat what we want. But our body just doesn't absorb the calories. Okay, this, this was the other way. And that, once again, also had was was questionable effectiveness, and actually had horrendous side effects. No one liked it. Okay. And so what has ended up happening is the most successful class of drugs is what we're in at the moment. And these are weaponized gut hormones that gut hormones that have been modified, they they self home, shall we say, to the brain, which is where a lot of them signal. And because most gut hormones make you feel fuller, if you actually take one of these naturally occurring hormones, increase their halflife, and they stick around the blood for a lot longer, they then end up signaling to the brain and make you feel fuller. And so these new class of drugs make you feel fuller, which means you eat less, which means you lose weight. And so that turns out to be the way the way to go. At least for now. At least for now.
Yeah, that makes sense. I think it was like 15% For some of them, and then almost up to 25% for the new Eli Lilly one.
Absolutely. And remembering that bariatric surgery, on average reaches about 30% mark. So now we are in the realms of looking at like you said the newest Lilly compound which is still which is still entering phase three. So that's the hat that has not been retro, retro retired, I think it's called. Yeah, it hasn't actually whatever the words are. It hasn't actually been been approved yet but yeah, that's approaching 25% weight loss in less than a year's treatment 48 weeks with no plateau. Yet of the of the weight loss. I was at the I was in San Diego at the American Diabetes Association meeting when they actually presented that data. It was very exciting and and unremarkable. So now we are beginning to approach the realms of bariatric surgery without the surgery, which is saying something.
Yeah, that's, that's incredible. Have you seen anything like that in the history? Like, what were kind of the percentages of the old, older, you know, absorbing or energy or whatever.
The absorbing what study absorbing once it's something is still in the market, incidentally, is cool orlistat and that, it says prevents you or prevents you intestinal wall from actually absorbing fat. The issue is, while just as a segue, if I might, well, those drugs were designed to be a to prevent you from absorbing. So in other words, you can eat what you want. And so therefore, you don't actually absorb the calories, it comes out the other side, so so to speak, that's not how they ended up working, how they ended up working was because what it prevented was the absorption of fat specifically, rather than carbs or anything else. So I end with all apologies to your audience, if they're listening to this, when they're eating, what then happens is, you then ended up with fat coming up to the side, right? And, and so you have oily poo. Now, the thing about what you don't want, people got very, I'm not kidding you, the side effects were awful. So there was a you actually had a a relatively fatty diet, you ended up with leaky poo. It was awful. And so what how that drug ended up working, and that we were looking at the five to 10% Mark, okay, if the if the people were willing to actually stick to it was, the side effects of eating anything with fat was so bad, that people ending up really having quite a low fat diet. So it was behavioral modification, that particular that particular draft. So it's just I, whatever, okay, some people float some people's boats, I don't think it's going to it's going to do that. And then there is this, there is the earlier versions of the current class of drugs. So these are so called GLP, one mimetics. These are once again weaponized gut hormones. And these were single, a daily injections, achieved 10 to 15%. Now, which is fine, actually, because a 10%, a 10%, weight loss for anybody is enough to give you measurable health benefits, can I mean, you know, you're fine, you're not going to be super, super healthy, necessarily. But it does take down and really reduce your risk of another of these morbidities that are associated with with obesity. But then it's these new class of drugs, which are now almost all once weekly injections, which means that you don't have to inject yourself every day, and really super long have super long half lives. And actually, through some unknown mechanisms, we still don't know. It either improves access to the brain, or now they talk it target multiple gut hormone receptors within the brain to become now the super effective 15 to 25% effectiveness. So relatively speaking, this is something that's kind of the that's the history of potted history of it.
Okay, yeah, that makes a lot of sense. Um, cool. Um, so, let's see, before I forget, this is on my list, can you just tell me like your name and what you do, you know, just Hi, on your girls. And
so, my name is Charles yo, and I am a professor of Molecular neuroendocrinology. At the University of Cambridge, neuro we know, endocrinology is a study of hormones, molecular, we know. So I study the molecules, which signal from the south of the neck to the north of the neck, broadly speaking, that's what I do. And I work here at the University of Cambridge, which is why I'm interested in these drugs because they have suffered and they're communicating with North Atlantic. Perfect.
Great, ya know, that. That makes I'm trying to wrap my head around what they're doing and how they're doing it and all of these things. Yeah. Um, interesting. So, um, what kind of, they'll go ahead.
No, so do you do? Would you like to know how these drugs do work? Yeah, sure. Yes. So now when I see when I say that they're weaponize gut hormones, like what what do I mean and what do governments have anything to do with making you feel fuller? Okay, so your gut hormones are there to regulate flow of flow of material through the tube? Okay, from here to that out? Yeah. And we know 20 gut hormones 18 of which make you feel fuller. So at the moment, they may be more ought to be discovered. But at the moment we know of 2018 of which makes you feel fuller. Now your governments do a couple of different things, some of them signal to your pancreas to enhance the secretion of insulin based on what you eat, which is why these drugs are also a what originally actually designed as a type two diabetes drug, rather than actually having anything to do with obesity at all. Okay, that was there, that was the initial design, the weight loss was a side effect. What that happened, people find them hang on a second, if we if we increase the half life of these governments, and these gut hormones have very, very short half life, two minutes, okay. So they normally get chopped up within within a blood within a couple of within a couple of minutes, you extend them to daily or weekly, they kick around a blood a lot, a lot longer, then they get to the brain. So within the brain, they then signal so largely to the brainstem, which is behind here, the more visceral effects so you know how you can be comfortably full, you can be very full, you can be oh my god, I still feel so full, I feel like pooping. And so those are mediated by by your, by your gut hormones. And so broadly speaking, what these drugs do is because you have a tonic higher level of just a single hormone for something like ozempic, just GLP one, a tonic level of of a hormone that's slightly higher than you normally would get when you actually eat, you feel fuller, you eat less, you eat less you lose weight. So that broadly speaking, is, is how these are how these drugs work. Now, there are side effects. If you were gonna ask me about side effects, there are side effects. And the side effects once again also reflects the biology of the office system. So another physiological role of what these gut hormones do is to make you expel food quickly when you need to. I eat during food poisoning, okay, so if you have something bad, bad from a bad friend, and you suddenly rented rented a toilet or rent to go to the restroom, what happens is you actually get a huge spike in government, and this makes you puke. So hence, the most common side effect or the bulk, although still relatively rare, particularly if you take too high a dose is nausea. Okay, so that is that will picked up the trials. The other side effects are either constipation or diarrhea, this is obviously the speed either too slow or too fast, for the other reason, because they also regulate flow through through the system. So that is why that is how they work. They make you feel fuller, they improve your insulin secretion, okay, type two diabetes and obesity. But that's why the side effects also come in.
Gotcha. So were they originally just affecting the pancreas and then like they were shorter, so then they were just kind of affecting the pancreas and insulin creation, and then they moved on to bigger and better things for longer lasting to where it's affecting the brain.
So the original biology, particularly of GLP, one GLP, one is actually called an incretin hormone. So within so why is it called an incretin hormone because type two that well, people who study blood glucose realized there was a difference between insulin levels between eating sugar and injecting yourself with sugar. So if you inject yourself with with with glucose, or whatever, any kind of sugar, your insulin levels go up, unsurprising, that's, that's what it does, but when you actually ate the sugar and the sugar therefore, had to go through the gut wall into your blood, there was an enhanced significantly enhanced secretion of insulin. And that is because of a rise in GLP one and chip which is the other one, okay, a rise a GLP one which that enhanced secretion of insulin incretin. So, this was always the biology of system. So the drugs were designed to take advantage of this for type two diabetes, the weight loss came when when as a side effect where people realize oh, people are losing weight, and then people will also at the same time it okay, there was overlapping understanding of the science behind this, where people were also trying to understand the biology of bariatric surgery. Now, what happens with bariatric surgery is you the most popular one is ruin why? And what happens there is you reduce your stomach to about the size of a tablespoon per volume of a tablespoon, which is not a lot. So 1530 mils, couple of tablespoons, and then they take away about a metre of gut to duodenal Okay, so just coming out of the stomach and they replumb it and that it was designed, it's permanent. It was designed to prevent absorption, okay, or at least to reduce absorption and that's how they thought it would work. You reduce your stomach size, you want to eat less, you reduce your gut length, you absorb less Now as it turns out, that's not how it works because what then people begin to realize was that people's type two diabetes, okay, if they were type two diabetes because they had obesity was was normalized overnight after bariatric surgery, clearly before any weight loss occurred, okay, because it's overnight because it's overnight. And so people went well, that can then be because of the weight. And it has to do because of hormones. And so what in effect has happened is because you've removed a section of gut. And as food goes through the gut hormones are released, food that is slightly less digested, is being moved further down the gut, resulting in this release of these different hormones. So people go, and so and then people begin to realize the Type Two Diabetes effect, but also the fact that gut hormones tend to make you feel full. So I mean, it's not a really a clear linear story. But then people began to put together all the jigsaw pieces to say, well hang on a second, type two diabetes, bariatric surgery, making you feel fuller, less like a drug specifically to try and do the weight loss elements to it. Gotcha.
Okay, that that makes sense. Cool. Um, so I think I don't want to take too, too much of your time. I know I said, 1520 minutes. So
sorry, I took them I took a lot you should tell me to shut up. No, no, no,
it's great. I need it all. Let's see. So I think I think just about all my questions, and oh, one more um, do you have time? Um, other companies are racing to make similar drugs can make practice easy, like just a flood of the market and then prices go down or Oh, no, my laptops today? Once again,
yes. All right. Don't worry.
Next Okay, there Yeah. Yeah. Okay, anyway, we're seeing a flood seeing, are we gonna see them flood the market? Like, what do you what do you think's gonna happen?
So, it is a very interesting time, as I said, the one the drug that has has came first on the market and so therefore, at the moment are still the market leaders because they will first up is ozempic slash we go v. So some of you type from Novo Nordisk, but as you know, there's a huge shortage of the drug. Now, interestingly, it's and so therefore, prices are high. And in the United States, where there's a privatized healthcare system, there are now people with money that can get more access to it. Whereas in other countries, the UK, for example, with another national healthcare system, where we can't just go and buy drugs, no, most of us can't. Anyway, we're getting a shortage of this. Now, what is interesting is that shortage is not down to the actual drug itself, they're made in steel vats somewhere, there's no shortage of the drug, the shortage is in the delivery system. Because when you actually are selling this, you need a system that delivers a precise dose at the right amount in a clean safe delivery system. And it's the plastics, the metal, the glass within the system, and that that isn't shortage. So they're trying to up they're trying to up there, they're manufacturing, the same thing is being faced by Lily, making Manjaro, which is, which is tourists appetite. And that has around the 20% effectiveness mark, they have the same problem with with manufacturing, the delivery system, prices are still very high there as well. But as more and more of these drugs hit the market, and they improve the manufacturer of the delivery system. And they become orally available on some of these some of these products, then I think the price will begin to the price will begin to drop, and then we will get people who really need it getting it. I think there's still always a danger like it is now of people trying to use it as a red carpet drug or Beachbody drug, you know, where where there whispers of people in the red carpet using them you wish I mentioned names, but it probably is true. And so let's see, let's see what happens. I do think that these drugs should maintain on prescription, at least for now. And a big part of the reason is the safety data for the specific week long injections, okay, have only been available for two, three years. So I know the whole class of drugs has been around for 10 to 15 years. So I think the class of drugs should be generally safe. But you never know when you make a new formulation. It lasts for a week rather than a day. What other things could they be turning on? What other things could they be tweaking, so we need to really have a little bit of a better understanding of their long term safety profile. Some some rare side effects are beginning to emerge now that millions of people are taking it for example. So we need to understand the full profile of these drugs before before they become Tylenol. The Long Way for becoming Tylenol. I want to point out, but you know, there is a hope there is a whole are, you know, at the moment we manage all I've got a fever, you know, I've got back pain, you go to the you go to the drugstore, and you get these things, and you saw me sort of take a break. And so if we could actually achieve this with weight loss, if why wouldn't does not be wonderful?
Yeah, I can think of somebody that are going in having this argument that like, well, if it does come as widely available as aspirin, you know, is this going to cause this problem where people don't try to do any type of behavioral changes? First, they're just like, Oh, it's okay, I'll fix it, you know, and then they're just constantly on this drug.
So they'll have to be constantly on his drug. So yes, and this, this is the thing, right? So while most people are going to have to be so if you take the the example of high blood pressure medication, okay, where we know it's safe, people are now on it. I know people who are on high blood pressure medication, when you're on the drug, your blood pressure is normal, the moment you come off the drug, your blood pressure goes back up. Again, the same thing is going to be true for these drugs, because what these drugs are telling us is that our how hungry you feel, or how full you feel after a meal is down to your hormones, which it is. And so if you have a slight hormonal deficiency, which you have to replace, okay, in order to fix this, the hormonal deficiency is always going to be there. So these drugs are going to be there, and I gotta be there. If a lot of people take take them. For a lot of them, it's going to be it's gonna be fun life. Now, as I said at the I don't know the outset of the interview, I've suddenly been on record saying this, but these drugs treat obesity, they don't prevent it, which means that it doesn't stop you eating ice cream. I like ice cream. Incidentally, what it does is it makes you eat less ice cream. So I think to prevent obesity, we still need to improve our diets. We need to improve the access to healthy foods, we need to solve poverty, we need to make exercise easier for kids. We need to teach kids how to cook whatever with disgust, you know, all of these things. And so I think we need to use the right tool for the job. So use a screwdriver screwdriver for screws and a hammer for nail. This these drugs are wonderful for treating obesity. We still need to tackle our diet, our health, our exercise, our poverty, and educating our kids.
Gotcha. Yeah. Perfect. That That makes a lot of sense. Um, yeah. Okay. Do you have anything else you want to say about it? No, no, perfect. All right. Well, I think that's that's all my questions. And I can I can let you go. Thank you so much.
Thanks, Mary. Yeah, I do I do. I leave. You got to be safe. Your recording has nothing to suddenly disappear. Poof.
Yes. It'll be good. I'll go ahead and the meeting and then it'll download on my computer and we'll be all set.
Yes, definitely let me know if and when it comes out so I can share it, etc, etc.
Absolutely. I'll be it should come out this week on Thursday. Okay, yes, unless something bad happens. We'll see. Ya, thank you. Have a good day.
