Rejoice! Incretin mimetics may spell the end of obesity (PODCAST E55)

it's the Adam regusia podcast episode 55 and we are talking today about incretin memetics the hot new Pharmaceuticals that mimic appetite and energy regulating hormones naturally produced in your gut in response to the food that you eat or don't eat this is the new generation of anti-obesity anti-type 2 diabetes drugs you've probably been hearing about lately ozempic is the brand name that you're most likely to have heard about at this point but there's lots of others in big pharma's big old money sucking pipeline I'm not mad about it I mean for all the things that are legit evil about large pharmaceutical companies I reckon that the interests of big Pharma and little me coincide more often than they conflict when it comes to these drugs I say Shut Up And Take My Money big Pharma Mount jarrow is the unpronounceably stupid brand name of another drug that looks even more promising than ozempic according to studies on Mount jarrow that were published this past week and we're going to read through those in a minute Eli Lilly is pushing for fast-track government approval of that one here in the U.S it's already approved for diabetes they're trying to get it approved for weight loss these drugs have been in the news for good reason based upon my Layman's reading of the scientific literature on this topic and also on my probably much more valuable constant correspondence with actual scientists who work in this field I am ready to say it I'm gonna say that I think there's a good chance that this nearly Global pandemic of obesity and metabolic syndrome we're all living through is about to end not all at once and certainly it won't decline of the same rate among all the peoples of the world and it'll never go away entirely obesity high blood pressure high bad cholesterol type 2 diabetes heart disease and stroke these will probably all be with us forever to some degree as they always have been but the particular crisis that these problems present in our world today the massive scale of the crisis I think this is the beginning of the end of that I think this class of drugs is about to change profoundly the way that human beings relate to food and it's going to be a good change in my humble opinion and no big Pharma is not dangling any checks in front of me to make me say that you don't have to pay me big Pharma I want to pay you take my money I've been saying for years that I think most humans in developed economies should probably be on pharmaceutical appetite suppressants to reduce all of the bad things that happen when we consume way too much food and that list of bad things is not at all limited to individual health or to fickle cosmetic concerns overeating is also really bad for the planet and all of the systems of production we rely on and overeating is a near certainty in developed economies where food is abundant and cheap and lifestyles are relatively sedentary we are evolved to overeat whenever possible because were evolved for a world where food was scarce and only intermittently available and we needed to expend way more energy to get it in the first place most of the people within the sound of my voice right now do not live in that world anymore I've said for years that regular routine use of an appetite suppressant would be a technological adaptation to Modern Life totally in tune with all kinds of other adaptations to Modern Life that we all take for granted like the clothes and the shoes and the toothbrushes and the eyeglasses and the vaccines and the wisdom teeth extractions and all the other technologies that we that we use to live and thrive in an environment for which our bodies are not evolved problem heretofore has been the lack of any good appetite suppressants every such drug that big Pharma cranked out until now has been trashed for the use that I have in mind for it I mean I'm sure the old drugs really do help in certain individual cases but the central nervous system stimulant diet pills of yesterday simply don't do that much and they have side effects that are too dangerous and too common those old drugs cannot be the population level cure that I have been hoping for now it looks like we may actually have that cure the Cure is maybe too strong a word to use look I'm just an idiot with a microphone and so the stakes are very low if I make predictions that turn out to be wrong but that won't stop me from making predictions that might turn out to be wrong and here goes let's say 10 years from now I think obesity and other diseases that are caused by or aggravated by overeating I think all of that will have all declined in rich countries to such an extent that you will see the difference in your everyday interactions with other people like you're going to go to the mall or to the football game or any place where lots of people congregate and you will notice that most people just aren't nearly as big as they were back in 2023 all of these strides that people have made in combating fat phobia all of that very laudable progress will be rendered mostly moot because in 10 years time I'm predicting that most people in rich countries who could benefit from a really effective weight loss drug will be on one and the drugs will work really well on most people people in the clinical trials have been losing an average of 15 to 20 percent of their total body weight within about a year on these drugs depending on which drug you're looking at so I weigh 200 pounds 90 kilos ridiculous as it may sound I am technically in the obese BMI category imagine me 40 pounds 18 kilos lighter after a year of just taking a drug that's the kind of weight loss where you start to look like a slightly different person and I have a full episode about whether it's actually bad for you to be fat short answer is no one is totally sure if the fat itself hurts you really bad but we we do know for sure that pretty much anything you do that makes you less fat will also make you healthier up to a point being very thin is also not a sign of good health obviously but the correlation between a reasonably lean body and a healthier longer life is about as strong as any correlation in epidemiology I'm getting older and some of my blood work is on the edge of not good and my lipid panels and other key indicators would almost certainly improve if I just ate a little less and that's what these drugs help you do without extra hunger pangs or fatigue or fuzzy headedness or conscious sacrifice of any kind you just take the drug people who are on them describe just forgetting to eat sometimes all with negligible known side effects in most people this is going to change things in rich countries first for obvious reasons but the drugs will probably eventually be accessible to most people in the world who could use them and overeating is in no way unique to rich countries or to Western countries yeah the U.S has the highest obesity rate of any large country but Saudi Arabia and the rest of the politically stable Middle East is coming up right behind us with their obesity rates which are also Sky High I mean about half of people in the Kingdom as they say are overweight or obese by conventional epidemiological standards here in the U.S we're up to about 70

percent overweight or obese but that's probably just because we got started industrializing earlier obesity isn't a massive problem in mainland China yet but it's getting bad in the cities and other aspects of metabolic Health among Chinese people are just as bad as they are here in the U.S probably because their typical diet is getting pretty horrific too and it's all about to get so much worse as the Chinese population ages dramatically due to low birth rates and low immigration this is not a rich country poor country thing it's more of an urban rural thing when people leave traditional agrarian life behind and they move to cities to work industrial jobs or post-industrial jobs basically everything about life changes and urbanization is a global phenomenon urbanization is great in lots of ways that's why all the cool kids have been doing it for the last 200 years or so but obviously urbanization results in the explosion of all kinds of ills among the most significant being infertility biological infertility and social infertility I really like babies I've helped to make some babies and I encourage you to make babies if you've not already done so but even I can admit that making babies is basically an active economic self-sabotage in an urban industrial or post-industrial context back on the Family Farm you're ancestors needed to make babies to make farm hands and to have enough surviving productive adult children to take care of them in their old age in a less productive economy like that it really takes a lot of working young people to support just a couple old retired people our economies are far more productive today so it takes fewer young people to support the old people and on the individual level people don't even need to have kids to support them anymore you can just pay taxes into social welfare systems and you know rely on them to pay out an old age pension for you whether you helped to propagate the species or not in a Modern urban context on the individual level it makes less than zero Financial sense to have kids and Modern urban people have better access to education and contraceptives and economic opportunities that require them to work outside the home away from their families so they're increasingly just not making babies or maybe they make one baby for every two people and this is going to result in some localized population crashes in our lifetime like there's 50 million South Koreans living right now and by the end of the 21st century the UN is predicting there will be only 20 million South Koreans this is due chiefly to lack of baby making despite the best efforts of the boys in BTS to inspire baby making and to personally contribute to the effort through their no doubt prodigious in-house baby making program over there at BTS headquarters I bet some of them are hard at work this very instant I purple you the planet would probably be a healthier and nicer place to live with a smaller human population especially as everybody in the world starts to live like a wealthy Westerner like me consuming way too much so I'm hopeful this urbanization Associated decline in baby making will actually be a good thing long term but in the medium term it's going to be a disaster for pretty much any rich country that won't let in enough immigrants to compensate and even in the most productive economy in the world there won't be enough young people working to subsidize all of the retirees and the result will be Galloping inflation and some degree of social breakdown all of which were arguably starting to see already in places like Japan it doesn't matter how much money you save for retirement or how big a pension you get if there aren't enough working people to actually produce the goods and services you hope to buy with that money so inflation my guess is we're going to figure out Solutions as we always have before at some point with our top heavy demographic structures tumbling over and shattering we're going to actually commit at the societal level to make Urban baby making affordable and desirable for a lot more people and hopefully we'll figure out why biological infertility is also on the rise that probably has a lot to do with what we're eating these days obesity is associated with infertility the Plastics in our food and environment may be messing with our hormones but I think we're going to figure out the baby making problem and get the demographic ship stabilized crazy population oscillations will probably be remembered as this weird blip that we experienced as a species during our rapid and tumultuous transition out of The Agrarian life that most of us had lived for the few thousand years previous I'm pretty confident in that but I am even more confident that the Obesity pandemic will be regarded as a weird little blip in our history because it appears that the end is nigh in our lifetimes I am predicting the near eradication of major high body fat related problems and in the richest countries I'm predicting that it happens within the next 10 years or so so now we're going to talk about what exactly in cretan memetic drugs are how they work what's good about them what's bad about them how much they cost which is a lot at the moment we'll talk about which of these drugs are available now and which will be available soon and how people are getting them Etc and more importantly we're going to try to imagine what the population level transition out of obesity is actually going to look like how will the end of the Obesity pandemic change us socially and culturally I'm gonna make some totally unaccountable for infotainment only purposes predictions about the societal impact of these drugs but first i'm going to thank the sponsor who is making all of this possible which is lmnt it's actually a pronounced element but this is a radio program so it's spelled lmnt pronounced element check them out at drinklmnt.com Adam to get a free sample pack with purchase wow has element been saving me lately it is a delicious electrolyte drink that helps to replace crucial minerals that all of us need but we particularly Hemorrhage with great athletic effort or sometimes just summer heat hmm delicious if you sweat a lot drinking plain water only does so much for you eventually you'll need to replace all the salt you're sweating out otherwise you will not be able to retain the water that you're drinking this is why athletes engaged in Long practices or endurance athletes in competition drink electrolyte drinks but they're not the only ones who could benefit if you're on a really strict diet if you're eating zero junk food you could easily become electrolyte deficient simply from lack of food or lack of the particular food from which most people in most developed countries get most of their salt in their diet which is from Ultra processed foods it's probably good for most of us to avoid Ultra processed foods a bit but not getting enough salt actually is a problem for some people and there's lots of research on this you can consult at elements website and elsewhere they've read the research and they've come up with their optimal blend of sodium potassium and magnesium all packaged in a convenient little powder that dissolves readily and it's zero sugar they sweeten it with stevia so it's simple delicious flavorings like citric acid and that's it there's no weird colors nothing else I do drink elements during long hot workouts but lately it's been a lifesaver because I've had this weird stomach thing going on my stomach is really inflamed and mad at me about something it hurts when I eat I've been vomiting a little and I've had almost no appetite for the last week yes I'm going to the doctor soon I'm just waiting for my appointment but in the meantime I'll drink a tall glass of element and feel immediately better if you're not eating you're going to run low on electrolytes and you're gonna get headaches and muscle cramps and fuzzy headedness and all kinds of bad things that we tend to blame on the stomach bug or whatever it is and I'm sure it contributes but whenever I've been sick like that I've always been sure to grab an electrolyte drink and I immediately feel resurrected hmm you can get a free element sample pack when you uh make any purchase with my link which is drink lmnt.com Adam try all the flavors or maybe give the sample pack to a friend you can only redeem that offer with a link like mine which is drinklmnt.com Adam thank you element so

what does incretin memetic mean well memetic just means mimic it's a drug that mimics or impersonates the increase that your body makes naturally and in cretins are a category of hormones named in the 1930s by a Belgian scientist called jean-labar I wonder if he's named after the 18th century jean-labar who was executed by Catholic authorities in France for reading Voltaire look that guy up he was basically an 18th century college kid who was tortured and beheaded and burned with voltaire's philosophy dictionary nailed to his chest nobody expects the Spanish Inquisition anyway the 20th century Jean Le bear had been studying insulin for many years uh when he and his colleagues at the University of Chicago first identified the existence of incretin insulin is not an in cretan though they are related as you'll soon understand labar was trying to figure out how the pancreas quote unquote knows to secrete insulin when you've eaten carbs you eat sugar or you eat starches that your body breaks down into sugar glucose specifically the food goes down through your stomach and into your intestines where the glucose is absorbed through the lining of your small intestine where it proceeds into tiny little blood vessels connected to your intestine and that's how glucose enters your bloodstream or it's one way glucose enters your bloodstream you can also access glucose from your liver and such but that's how you get blood glucose directly from food once a bunch of glucose is in your blood it's dangerous it's bad to have high blood glucose your bloodstream reaches basically every living cell comprising your body and too much glucose in the blood will damage cells and tissues in lots of different ways so this is one reason why you have a pancreas you know lots of objects in this world kind of resemble an erect male member so much so that grown-ups like you and me we rarely even comment on the similarities it it simply isn't that remarkable to us when something kinda looks like a dong but the pancreas really really looks like an erect male member and the proportions are just right it's about six inches long in most people 15 centimeters that is the average length of the aforementioned engorged human male reproductive organ and honestly I don't know how much a real pancreas in the wild actually looks like this but the way they draw the pancreas in anatomical illustrations wow it really really looks like a dong it's tucked right behind your stomach and one of its functions is to make digestive enzymes that it sends via a system of ducts into your small intestine where they they help to digest your food for example the pancreas makes the enzyme amylase which breaks starch down into glucose and it's so good at doing that that eating pasta or something is basically the same as eating candy though we don't think of it that way for some reason nobody talks about kids getting a sugar high from noodles but they absolutely could get a sugar high from eating noodles another job that pancreas does is it makes insulin which is not an enzyme enzymes are proteins that we use for jobs other than being the raw material of muscle or some other tissue which is the main thing we use proteins for but we also use proteins to catalyze biochemical processes and those proteins we call enzymes amylase is an enzyme insulin is a peptide and peptides are components of proteins proteins are made up of peptides which in turn are made up of amino acids peptides do combine into proteins but they can also stand alone and function as hormones hormones are signaling molecules your body basically uses them to convey messages from one cell or tissue or organ to another the message effectively carried by the insulin is hey cell I've got some glucose from the bloodstream here take it you eat carbs glucose flows into your blood your pancreas releases insulin that binds to receptors on your cell walls not all of your cells but your your fat storage cells and your skeletal muscle cells are like the two big examples of tissues that need insulin for glucose uptake your pancreas releases insulin that signals those fat and muscle cells in your body to absorb that glucose through their cell membranes and into their cytoplasm and they use the glucose to power their operations in the case of muscle cells in the case of fat cells they use glucose to store energy for you for later assuming you ever use it if you don't actually use it well you know you get fat if your pancreas releases too much insulin too much of your blood glucose gets absorbed into cells and you go hypoglycemic not enough sugar in the blood you get light-headed confused tired hangry and when it gets really bad you get the shakes and eventually you pass out and maybe you have a seizure and maybe you die that's hypoglycemia and it can also be caused by just not eating enough that's obvious right and the pancreas makes a hormone for that event too called glucagon glucagon is basically the opposite of insulin insulin tells your cells to suck sugar out of your bloodstream because there's too much sugar in there while glucagon tells your liver to release stored sugar into your bloodstream because there's not enough sugar in there your liver stores energy in the form of glycogen so glucagon tells your liver to break that down into glucose and to dump it into your bloodstream to maintain optimal blood sugar levels if you have way too much sugar in your blood due to excess glucagon or insufficient insulin or way too much junk food or whatever if you have way too much sugar in your blood you go hyperglycemic too much sugar in the blood first you might notice that you're really thirsty and you have to pee a lot this is because glucose is an osmotically active molecule it effectively pulls water across membranes you might also feel weak and tired if you're hyperglycemic and then if you stay hyperglycemic a bunch of weird stuff starts to happen your vision blurs your mouth is dry but your breath smells fruity that's because of ketones and that's why people on a truly ketogenic diet tend to have weird breath you might feel hungry with hyperglycemia but eventually you'll feel sick to your stomach and maybe throw up and you'll feel short of breath and confused and eventually you pass out and maybe die that's acute hyperglycemia way too much glucose in the blood all at once then there's chronic hyperglycemia a little too much glucose in the blood over years and years and years that does all kinds of awful things to the body it interferes with the function of neutrophils which are a kind of white blood cell very important for your immune system and as a result chronic hyperglycemia makes you more susceptible to infections and diseases of many kinds and wounds don't heal as fast and chronic hyperglycemia just slowly kills your body piece by piece it hurts the blood vessels themselves obviously it leads to atherosclerosis and therefore heart attack and stroke other tissues are especially susceptible like nervous tissue resulting in uh neuropathy and therefore pain or numbness in the legs and the feet especially and this can eventually lead to you getting little Cuts or sores that you don't notice because you can't feel them and they're less able to heal because blood flow is restricted and your neutrophils are functionally impaired and all kinds of other stuff and so the the infection gets really bad and they have to amputate your foot or your leg to keep you alive all of this should be sounding familiar at this point right I am describing Advanced stage diabetes this is what bad diabetes does to you we'll get back to diabetes but the way a healthy body prevents hyperglycemia is the pancreas releases exactly the right amount of insulin at the exact right time to make your muscles and fat cells absorb the right amount of glucose to keep your blood glucose at just the right level which is about a hundred milligrams per decimal liter of blood assuming you've not just eaten if your fasted blood sugar is above 126 milligrams across two separate tests that is a clinical definition of diabetes in a healthy non-diabetic person how does your pancreas know exactly how much insulin to release and when to release it to manage your blood glucose I mean the pancreas is not part of your alimentary canal the elementary Canal being the big long pipe that all of your food passes through in your body it starts with your mouth and the throat and then it goes down through your esophagus and into your stomach and then down through your intestines and eventually out the bunghole that's all one big pipe through which your food flows and they call it the alimentary canal your pancreas is an accessory to that pipe it's kind of hanging off the side of that pipe behind the stomach but it's not a section of the pipe food does not flow through the pancreas so how does the pancreas know what you're eating and therefore how much insulin it should release well the science of all that is super complicated but about a hundred years ago jean-labarian company observed that this process involves hormones created in the gut in your intestines your food does pass through your intestines obviously so your intestines know what you're eating they make and release hormones in response to what you do or do not send down the pipe these hormones play a role in signaling your pancreas to pump out insulin or not and these are the hormones labar called incretin in contrast to secretin which is a different gut hormone that isn't important right now today we understand that in is actually at least two distinct hormones it's glucose dependent insulinotropic polypeptide known as Gip and the other one is glucagon like peptide one glp1 Gip is made by cells in your upper gut glp1 is made in your lower gut those are your incretins they help signal your pancreas to release the right amount of insulin in response to what you have eaten this is known as the incretin effect and it is broken in people with type 2 diabetes type 1 diabetes is a totally different disease that just happens to have similar effects type 1 is an autoimmune disease that people seem to get as a result of genetic and environmental risk factors no one knows why it happens but your own immune system attacks and destroys the beta cells in your pancreas that make insulin there is no cure all you can do is Survive by constantly supplementing with outrageously overpriced insulin made not by your pancreas but by your friends at Big Pharma and right now people in more civilized countries with more civilized Health Care Systems are probably thinking insulin costs you something yeah like hundreds or even thousands of dollars a month in the U.S for insulin just to stay alive anyway that's type 1 diabetes it seems to be mostly genetic it usually starts up when you're a kid and there's really nothing you can do about it other than shoot up exogenous insulin all the time for the rest of your life and if you shoot the wrong amount of insulin at the wrong time you could end up killing yourself it's a bad gig having Type 1 Diabetes Type 2 diabetes also really sucks but it tends to hit you later in life it's more preventable and it's more treatable especially now instead of your immune system killing the pancreatic cells that make your insulin what happens with type 2 is something else interferes with your natural insulin production and or your muscle and or fat cells become resistant to insulin the insulin says hey I've got some blood glucose for you and the cell says no thanks we're good and they don't absorb the glucose so the glucose builds up in the bloodstream and you become hyperglycemic it's important to remember that no one fully understands what causes type 2 diabetes some people seem to get it for no apparent reason they're otherwise healthy fit trim eat a good diet exercise and they get type 2 diabetes anyway no one knows why so you shouldn't assume that anybody with type 2 diabetes got it by Leading an inadvisable lifestyle but it is also true that being overweight and eating a ton of junk food and drinking a lot of booze and not getting any exercise are all giant risk factors for type 2 diabetes it seems like part of what happens is you just dump way too much sugar into your blood all the time the pancreas pumps out insulin to push it into your cells and your cells say seriously more sugar and eventually they stop answering the door when insulin comes on knocking that was probably a particularly crude oversimplification on my part it might not quite work like that but however insulin resistance happens you can treat it by simply injecting more insulin into your body to compensate so type 1 and type 2 end up being very similar diseases in effect even though they seem to have totally different underlying causes the difference is Meaningful in the sense that you can improve your type 2 symptoms a lot by simply improving the lifestyle that may have caused the disease in the first place or contributed to it you can massively reduce your dependence on insulin from Big Pharma by just eating less junk food and getting more exercise people say that losing weight improves your type 2 symptoms but that's kind of a shorthand no one knows for sure if losing the weight is what lowers your insulin resistance or if improving your diet lowers your insulin resistance and then incidentally also causes you to lose weight as we said in our video about whether it's actually bad to be fat this may be a distinction without a meaningful practical difference because most of the things you could do that would cause you to lose weight are also likely to alleviate your type 2 symptoms therefore it's probably simple enough to just tell people to try to lose weight it's the same advice in effect Maybe but one reason type 2 patients don't make enough insulin is their pancreas is unresponsive to Gip the incretin or gut hormone that stimulates the pancreas to release more insulin however the pancreas of type 2 patients is responsive to glp-1 the other big in hormone so if you could boost glp-1 in type 2 patients that might help their pancreas to do a better job regulating their blood sugar so for decades big Pharma has been playing around with type 2 drugs that inhibit the breakdown of your natural glp-1 or they simply tickle your glp-1 receptors and these are your increase memetic drugs in impersonators drugs like these have been coming on the market since the 2000s they were government approved to treat type 2 diabetes and as far as I can tell the people making these drugs thought about them as type 2 diabetes drugs not weight loss drugs at least early on in the development process but people taking them started to report dramatic reductions in hunger and they lost a lot of weight while their insulin and glucose levels also improved leading to some fascinating chicken or the egg questions did the drug alleviate people's diabetes or did it help people lose weight which alleviated their diabetes I imagine the answer is yes we have a better sense of why in cretan memetics lower your appetite and do other things that help you lose weight both glp-1 and Gip affect tissues all over your body not just your pancreas they influence your lipid metabolism they slow the emptying of food from your stomach into your intestines they may even stimulate your nervous system to expend more of the energy you eat by increasing thermogenesis body heat the mechanisms are many and complicated and not fully understood and I've linked to a literature review in the description if you want to read more if this episode proves interesting to a lot of people I could maybe do another one all about the specific ways that these drugs seem to reduce people's body fat regardless these diabetes drugs that started coming on the market you know 10 or 15 years ago proved incidentally effective for weight loss and so doctors started gradually prescribing them for weight loss even though the drugs were not government approved for weight loss that is called off-label prescribing and it's generally legal though not necessarily ethical or smart and this leads us to ozempic the glp-1 receptor Agonist that everybody interested in Fat Loss has been talking about for the last few months I'm gonna tell you all about that but first let me tell you about uh Magic spoon cereal sponsor of this episode save five dollars at magicspoon.com regusia Magic spoon is a big part of how I try to replace some of the car in my life with protein the Magic in the spoon is this particular milk protein blend that they use in place of grain in these delicious sweet little crunchios there is no grain at all in Magic spoon it's gluten free for people who are sensitive to that zero grams of sugar it's sweetened with a very smart blend of Alternatives like we discussed in our episode about low and no Cal sweeteners and the fruity flavored box that I have here has four net 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Canada and the UK too thank you magic spoon okay the glp-1 receptor Agonist sold as ozempic the scientific name is smaglitude no semaglatide there it is smaglutide but I'm gonna go with the trade name ozempic just because that's what everybody knows and I'm pretty sure how to pronounce it ozempic was developed by the big Danish Pharma company Novo Nordisk which I always think sounds like an antivirus software that my dad might have downloaded onto the family Mac in like 1996. oh I got CD-ROMs for AOL and Novo Nordisk the US government approved ozempic as a diabetes drug in 2017. the EU and everybody else followed suit shortly thereafter off label use for weight loss started to happen and then in 2021 the U.S approved

wegovi which is a higher dose version of ozempic explicitly labeled for weight loss the clinical studies show people losing about 15 of their total body weight after about a year on this drug and the secret got out everybody started asking their doctor about wegovi and Novo Nordisk was like sure that'll be 1 308 dollars a month that's literally the list price new drugs are usually super expensive because big Pharma has to recover their enormous research and development costs while they can not to mention their obscene corporate profits it gets hard for them to charge that much as a drug gets older and patents expire and cheaper generics come on the market Etc so drugs tend to be expensive when they first hit the market also Novo noridisc seems to have not correctly anticipated the demand for this product because when supplies of wegovi ran low doctors started prescribing ozympic instead and all of the type 2 diabetics who rely on ozempic to you know not die were like oh crap the pharmacy is out of ozempic because Barbara wants to get bikini ready by Summer so real doctors ethical doctors not the internet doctors feel good who prescribe anything you want after a 30 second Zoom call but ethical doctors the kind you should actually see they started pulling back on prescribing any of these drugs for weight loss until the supply chain issues got worked out this is why a few months ago on the Pod when I briefly mentioned the enormous potential of hormone-based weight loss drugs I did not mention ozempic by name I just said these drugs exist and they're coming to a pharmacy near you soon I didn't want to contribute to the run on these drugs but now it looks like supplies are beefing up and other similar drugs are also headed to your Pharmacy the most exciting one being who boy terzapathide terzapatide terzapatide anyway Eli Lilly is selling this as Manjaro for diabetes I imagine they'll come up with a different brand name for when they get it approved for weight loss which looks like it will happen in the U.S late this year or early 2024. this new Eli Lilly drug is different from the others in a really big way ozempic is an as a glp-1 Agonist but remember there's another in hormone Gip and this new drug mountjaro or whatever they're going to call it this new drug acts on both glp-1 and Gip receptors and this seems to result in even more weight loss 21 of total body weights lost on average over a 72-week clinical trial the results of which were published last week that's really incredible that's the first drug that has gotten anywhere close to the results of bariatric surgery which is basically the only weight loss intervention that's proven both very effective and very long lasting by the way they think that bariatric surgery Works in part by affecting your incretion hormones it does more than just shrink your stomach so that you can't eat as much so 21 average weight loss over a year and a half we'll see how long the results stick but the early data looks really good and all by simply taking a drug that lowers your appetite and maybe makes you burn more of the calories that you eat again that would be a 40 pound weight loss on a guy like me 18 kilos that's really big and they'll probably come up with even better drugs like these big Pharma gonna big Pharma and in this instance I say let the expensive medicine making machine go Burr the more they make the more competition there is in the market the more economy of scale is realized as more people buy it hopefully the cost will come down and hopefully insurance companies and government Health Services will start covering the cost to more people as more studies are done that I suspect will show that people live healthier less medically expensive lives if they can stay lean with the help of these drugs indeed don't let me dissuade you if you need help losing a lot of weight I totally think you should talk to your doctor about these drugs right now and see if your insurance or your government or whatever will cover the costs because they might already what are the other downsides well first big thing is that these drugs seem to work on most people but not all people depending which drug or which study you're looking at something like 10 or 20 percent of people in the trials lost little or no weight and nobody knows why but that's pretty common for drugs of all kinds that's actually a pretty great success rate relative to other medicines that we take for all kinds of things maybe they'll find that one increase in mimetic will work for you even if another one does not there are some side effects mostly gastrointestinal nausea constipation or diarrhea that kind of thing but the sides are pretty mild in most people and they seem to go away after the first week or two you can ramp up your dosage slowly to to mitigate the the side effects there are more significant side effects for people who actually have diabetes the drugs can essentially work too well and your blood sugar gets too low but that can all probably be managed with your doctor's guidance you know finding the right dosage for you letting your your eating habits adjust Etc another downside is that most of these drugs you have to inject like a weekly injection but it is a subcutaneous injection so it's a tiny little needle the width of a hair and you can do it yourself at home there is an oral version of ozempic on the market a daily pill they call ribelous or however you're supposed to say that ribosis rebelsus let's go with ribosis I bet it is drug trade names are so deeply stupid but that's that one is only approved for diabetes as of now the oral one I would guess there are more pill versions of these medicines in the works I'm sure big Pharma sees gold here and I'm basically fine with that let the profit motive do what it does best promoting Innovation and competition and if they end up permanently hosing us with outrageous prices that are orders of magnitude above the unit cost of production as they do with insulin well we can cross that bridge when we come to it and those of you in more civilized countries that regulate the cost of drugs more aggressively will probably never have to worry about any of that I think we're headed into a post-fat world and let's take a second to imagine what that might look like I always wanted to be a futurist you know somebody whose job it is to fantasize about what's coming up with little accountability for being right because usually you're dead by the time your predictions prove either true or false I get to be a futurist right now I hope that an early effect of the widespread adoption of these drugs will be increased society-wide acknowledgment that obesity is a disease not a character flaw the very efficacy of these drugs testifies to the fact that obesity is a dysfunction of the energy regulating systems of the body sure this dysfunction is aggravated or catalyzed by the rapid enormous changes in diet and lifestyle brought about by industrialization and urbanization and yes individual choices can profoundly affect the course of the disease but it remains a disease and if you're way thinner than the next guy that may be because you have excellent impulse control but more likely it's because your body is energy regulating systems are functional thanks to some combination of genetic and environmental factors in your favor the next guy might be heavier than you because he's a glutton but more likely it's because his energy regulating systems are dysfunctional his body stores calories as fats prematurely when he actually needed that energy to move around and think and stuff so he's getting fatter and yet he's exhausted and starving because all his energy is going into fat stores and then maybe yeah he does become a glutton because his body feels so bad all the time but the only way he can feel good is to eat or something like that the exact nature of the dysfunction remains a subject of much much research but I think people are getting the message that obesity is a disease not a disgrace and it's ironic to me that the beginning of the end of obesity is coinciding with the beginning of the end of obesity stigma I mean honestly it might not feel to you like there's been progress on destigmatization but that's because you're probably younger than me I came of age in the heroin Chic 90s the bodies of most of the sex symbols of today are so much more realistic quite a lot of us have come to find that we appreciate a little meat on the bones the bones of others and ourselves I'm worried that every actor in Hollywood and every singer and every rapper and every influencer is gonna hop on in cretan memetics half of them already have if the tabloids are to be believed and in a year or two there's going to be way less representation of bigger people in Media of course that would also mean that the social value of being skinny is about to plummet right like some degree of scarcity is essential to the value of any asset right now being skinny gets you ahead precisely because it is rare and it's one of the few things that money can't really buy you I mean money helps believe me it helps it helps to have a personal trainer and a dietitian and a personal chef and plastic surgery and steroids and all that but it still can't get you all the way to maintain a lean body in the modern world you have to have some amount of genetic advantage and or exceptional self-control and willingness to suffer neither of which can be bought for any amount of money unless you're like Jason Momoa or something and a studio offers you millions of dollars to get ripped for a roll that could maybe buy your willingness to suffer for a time but other than that a lean body was the one thing money couldn't buy you and so it was socially Priceless now money can buy you an average 20 reduction of your total body mass in a year or two 40 pounds for me can you imagine me at 160 pounds the last time I weighed 160 I had visible abs I mean not many but like two visible abs I'm not even sure I want to go back to that I'd like to lose like 20 pounds cosmetic aside I think my body just feels better when it's a little lighter and I suspect lots of people are about to discover that their bodies feel a little more comfortable a little smaller is less stress on the joints less chafing less bunching Aesthetics and other subjective values aside I think they're objective physiological reasons why most people in the United States for example would feel a little better and live a little longer if they were a little leaner myself included and I think we're about to be it'll start at the top of the socioeconomic pyramid as most technological advances do but as competition ramps up and popularity explodes and economies of scale are realized and eventually patents expire I see no reason why these drugs won't become available to almost anyone in the developed world I suspect the net effect of that will be to make us healthier and longer lived as a species so I remain all for it but I do worry about social things I worry about the few people who aren't able to get the drugs or the drugs just don't work for them if they're very big will they be even more stigmatized than they are now simply because they will be so much rarer and peculiar to people what if everybody and their mother hops on these drugs we all drop 20 of our body mass and we simply retain our existing stigma and shame structure for body fat we might simply recalibrate the standards down proportional to everybody's pharmaceutical weight loss I believe that's called moving the goal posts and it's something we humans do quite a lot usually not to our credit or benefit or will the value system simply tip on its head maybe big will be in again as it has been before in Western society and is right now in some other societies I wouldn't hate that aesthetically speaking but otherwise the case for being somewhat lean is pretty strong especially as you get older a young body can thrive in the face of a lot of adversity not so much once you hit my age and Beyond if you think about those like beautiful Polynesian countries where lots of body fat is aesthetically valued that's awesome let's all move there but also people in those countries which are like the few countries that surpass the US and their obesity rates people in those countries really do suffer from much worse cardiovascular health outcomes some people may remain perfectly happy to pay the price to be big and all power to them but they deserve to know what the price is indeed these new drugs May create a new situation where nearly all big people have 100 percent chosen to be big and that's not such a bad vision of the future after all is it of course that would mean that in like 50 years they'll be lamenting this pop culture fetishization of fatness at the expense of Health people are killing themselves to be beautiful it has to stop I'm gonna say that's my prediction that scenario will play out in 40 or 50 years if I'm wrong no worries I'll be dead or extremely retired and before we retire this app of the regusia Pod let me throw out an idea I've been really liking the big single topic podcast episodes lately but I have been neglecting audience questions and I've been itching to do some rapid fire very short segments covering relatively small but interesting ideas so I was thinking about maybe trying a live regusia pod that's all q a or mostly q a I could most easily do that as a YouTube live vid and then upload the audio to the podcast feed shortly thereafter it could be fun so if you would want to slide into the chat box on an atom regusia YouTube Live program well watch my YouTube Community page and my Instagram for an announcement of when I plan to do that I'll probably give pretty short notice because I imagine that we'll get plenty of people into the chat no matter what plenty enough questions it might actually be nice to keep the group somewhat small also watch my professional Facebook page which is Adam regusia internet cook I recently started working with a company that is re-editing my entire YouTube catalog for Facebook video so if your mom mentions that your uncle shared an atom regusia vid on Facebook tell your mom to smash that like button okay make good choices talk to you next time

2023-05-04 11:10

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