A woman took a friend's Ozempic and her entire gut was cooked

0:00 Hi Dr. Bernard here. I have first hand knowledge of this medicine. Not because I take it, but because I’ve worked on it. I’m not associated with any organization now here so you are getting my unfiltered view. I’m not here to scare you out of your mind about these medicines. But I am here to tell you that you need to be VERY sure that you have a legitimate NEED to take the weight loss medicine, you’ve exhausted every single other viable option that doesn’t involve putting this in your body, because it can cause LASTING direct and indirect changes to your body. Now on the flip side if you do really need it, don’t ever let anyone shame you for taking life-saving medicine. The cases im about to tell you about are rare. But at least 12% of all adults in America have already taken this. That’s more than 30 million people. And with the oral tablet

0:47 formulation now available, this number is only going to increase. If it’s even 0.1% of people getting the problems I’m about to describe to you, that’s still more than 30,000 people. KT is a 50 year old woman, presenting to the emergency room with horrible nausea and vomiting. She tells the admitting nurse that over the last month, everyday she would just want to eat less and less. This progressive decline in appetite, was profound. At first, it started as not wanting to eat certain meals of the day. Then it became, not eating for DAYS at a time. A couple months ago, one of KT’s friends had recently stopped taking weight loss medicine, but had a giant supply leftover. She gave KT what remained and told her how to take it. And KT started taking it. Without seeing a doctor in person. Without getting a prescription. This

1:36 is definitely something you never want to do, because weird things started happening. Sometimes a sour sensation would drip under her tongue. Her eyes would quickly start to water as they would feel like they were squeezing out of her head. And she would empty her stomach in a way more intense than the previous time this happened, which was earlier that day. Nothing was consistent. She was taking this medicine for just a couple of weeks. Sometimes all of this would happen after she’d eat, and it made her think that it was heartburn. Or indigestion. But other times, it would just emerge out of nowhere. Same feeling. But no food at all. The burning would become so intense that it would bring her down to the ground. She’d take over-the-counter medicine for her stomach. Proton pump inhibitor. The pink Bismuth liquid. But every time she took antacids, she’d get dysgeusia, the sour, metallic taste

2:22 that emerges from the back of the throat. And the pain in her abdomen would still radiate to her back. None of this would go away. Maybe, all of this is because of stress, she thought. KT told doctors that a burning abdominal pain emerged over the previous month. On the upper, right side. Wrapping around to her back. When you look at an anatomical diagram, the right upper quadrant of the abdomen has organs that aren’t on the left. The body TENDS to be symmetrical, it’s just that… the digestive tract isn’t. The gallbladder is here. It’s connected with the liver. And as you go further towards the dorsal, or the back side, the pancreas is there. And just below the pancreas, is the right kidney. If there’s pain in this area, any one of these could have something wrong. And further testing gave doctors more clues. Hey, I got a quick request. If you’re learning something from this video,

3:10 and you’re not subscribed yet, I’d appreciate it if you did subscribe and come back to see the video that I publish next month too. I make these videos for fun, and I do it to teach people about medicine, about how our bodies work, and to show the conversations that we actually have in medicine. On average I’ve made 1 video a month, every month, since 2017. I genuinely enjoy making these videos, and I’m so happy to be able to share them with you. I appreciate you. A blood test reveals that KT’s kidneys, are shutting down. Wastes that should be removed from her body through her urine, are now floating around in her blood. And it’s not just this. Parts of her liver have died, and are also floating around in her blood. Her liver has shut down. If both of these organs are where she’s experiencing pain, this should make sense, except, when the kidneys and the liver fail… they don’t always hurt.

3:57 They don’t usually directly produce pain. Meaning, for KT, something else is the problem. But what? Doctors do a CT scan so they can look directly in to her abdomen. They thought they knew what the problem was, but the image tells them that it’s more than they thought. The gallbladder is connected with the liver. This is a small organ that stores excess bile, which is a fluid that helps digest fats that you eat. The liver makes bile, so these two organs work together at the Common Bile Duct. This is where the gallbladder and the liver join to release bile. The problem is the CT scan showed that KT’s bile duct, was dilated. There’s a list of issues that can cause this. But not only that, her stomach was swollen, with pockets of air and what looked like food material that was stuck there. Further down in her intestines, there was a massive stool

4:44 burden. This was clearly, several days worth of bowel movements that were just sitting there. All of this explains why her whole body hurts, but the scan reveals even more. Let’s start with the dilated bile duct. Why is it doing that? Well, given that 1) parts of her liver have died, that 2) her liver has shut down and 3) that the liver empties some of its contents through the bile duct, then it means that all her problems could be coming from liver. But we have to think this through. Sometimes, if a “tube” or a “pipe,” like a blood vessel or a duct, is dilated, it’s the body trying to respond to a blockage. If we’re thinking of the bile duct, well, gallstones are famously known to block flow. We call this a cholelithiasis. Chole from greek referring to bile. Lith also from Greek

5:29 meaning stone. And -iasis meaning a condition produced by something specific. Anyone who’s had one knows that gallstones cause horrible upper right abdominal pain, similar to what KT is experiencing, except, the scan didn’t show she had any stones. Nothing was blocking the way. This means her biliary dilation is non-obstructive. This narrows down the cause down to 2 things. In the hospital, KT’s nausea and vomiting continued to worsen. She told doctors that she had been taking prescription pain killers. Only a couple of tablets though. She had saved these from a knee surgery she had years ago. She didn’t take very many. And she had simply forgotten to say anything because it was so insignificant to her. Doctors decide to do one more imaging test. They take a camera, and send it down into her stomach

6:15 to directly see what that mass was. And the images told them exactly what they needed to know. Sometimes, food doesn’t digest all the way. And this could be because the stomach isn’t moving things along. The entire gastrointestinal tract is a giant muscle. And it needs to contract and relax the entire way through, in order to move things along. This is a continuous tract, so from your mouth to your other end is one giant tube. This mass that was found in her stomach was made of a collection of all the food that she’s eaten over the last several days. Piled up, into one semi-solid heap. This is called a bezoar. It blocks flow in the stomach, explaining why she couldn’t keep anything down. And as things stretched in her GI tract everytime she ate or drank, it would ADD to the pain that she was already having, because this was stuck in her gut. As the

7:01 muscles in her GI tract try to accommodate this, MAYBE the bile duct stretched out and dilated. But here’s the thing. The bezoar is in her stomach. This is the Upper GI Tract. But there was a massive stool burden in her INTESTINES. That’s the lower GI tract, after the bezoar. A blockage up here, shouldn’t also cause a blockage down here. Meaning, we still don’t know WHY she had the bezoar AND the massive stool together. What allowed these to form? Well, the stool means the intestines weren’t moving. But we also said this particular bezoar is because the STOMACH isn’t moving. So if we put these together, and say that the entire GI tract isn’t moving, then, both of these simultaneously, are caused by the same problem. Therefore, something slowed down, or paralyzed her entire GI tract. It also caused a dilation of her bile

7:50 duct. Fluids backed up. They stayed still and the swelling caused massive pain. But what does this? At this point, KT tells doctors about the weight loss medicine that she had gotten from her friend. Luckily it was an approved, manufactured product by a company, not a compounded one, where, it would be harder to verify exactly what it was. So they knew exactly what was going into her body. One of the side effects of this medicine, is that it slows down the GI tract. The exact phrase we use in medicine about this is “delayed gastric emptying.” This effect is partially how it was discovered in the first place. But sometimes, and this is rare, it’ll slow the GI tract down to the point, to where things don’t really move at all. Gastroparesis. Gastro referring to the GI tract and paresis referring to muscle weakness and partial paralysis. Delayed Gastric Emptying

8:40 and Gastroparesis are not the same thing. Delayed Gastric Emptying is normal with this medicine. It’s PART OF how it works. Gastroparesis happens, but is NOT NORMAL with this medicine. I didn’t realize that might be a controversial statement. I’m actually kind of surprised that academic institutions are putting it this way on their websites. But let me explain. The words Delayed gastric emptying refers to a side effect. The word Gastroparesis refers to a chronic disease, whereby someone has extreme abnormally… delayed gastric emptying. Before this became weight loss medicine, while it was still a diabetes medicine, one of the most asked questions was the fact that the dose had to be titrated up, so that patients could tolerate the GI side effects. There was an effort to ensure differentiation between

9:26 delayed gastric emptying and gastroparesis. In English, “delayed gastric emptying” implies that it’s just delayed. It’s temporary. It’s going to move through, it’s just a little slower than normal. Gastroparesis sounds like paralysis, which implies, it’s over. It’s done. It’s never coming out. And that gut of yours, is never moving ever again. But let me say it again: it sounds like that. Now you see the problem. Doesn’t mean it’s actually over. This is an unfortunate circumstance of English words, and at best, people might just mistake the 2 and their implications, and at worst, bad faith folks will use it to mess with people. Just know, you can expect this delayed gastric emptying to happen when you’re on the medicine. Gastroparesis is the very extreme case, which if you do experience while taking it, see your physician in person,

10:16 who you should have seen to get this medicine in the first place, bringing us back to KT’s case. Why does this medicine slow down the gut? We need to understand what this medicine is. Slowing down the gut is not the only thing that it does. The name of the drug class gives us clues: Glucagon-Like Peptide-1 Receptor Agonist, GLP-1 RA. Glucagon is a hormone, opposite of Insulin. What does that mean? Insulin is the HORMONE released after you eat a meal. It tells your body’s cells to take in the sugar from the meal, floating around in the blood. It’s an anabolic hormone, meaning that it tells your body to construct and build things, based on that sugar. And this provides them with energy. Glucagon is the opposite of that. If Insulin lowers blood sugar, Glucagon raises blood sugar. And it does that by telling the liver to

11:03 break down its stores of sugar. Whereas insulin tells the body to build things, glucagon tells the body to break down things, therefore glucagon is a catabolic hormone. So let’s go back to the name “Glucagon-Like Peptide-1 Receptor Agonist.” Science discoveries don’t happen in order. And this is where things might get a little confusing. the weight loss medicine KT took is based off Glucagon Like Peptide. And Glucagon Like Peptide, only LOOKS like glucagon. It also comes from the same place as Glucagon. But Glucagon Like Peptide doesn’t DO anything that glucagon does. GLP-1 is also a hormone. But it stimulates insulin release. That lowers blood sugar. But also, GLP-1 also prevents glucagon from being released.

11:49 This confusion is because science discoveries are often made out of order. And the location where GLP-1 was found in the body, was centered around glucagon, and the name probably wasn’t changed, because it took many more years to discover exactly what it did. Agonist means that the medicine pushes forward the GLP-1 signal. At a minimum, an agonist can be a fraction of, or match the signal. At a maximum it can multiply that signal. There isn’t some grand conspiracy behind this name INTENDED to confuse the masses. But just know that this name refers to the opposite of an opposite. Glucagon is a catabolic hormone. It’s the opposite of insulin. But glucagon-like peptide is the opposite of glucagon. It stimulates insulin, but it also isn’t insulin. The most important thing to know, is that because GLP-1 is a hormone, it does very many things to

12:38 the body, simultaneously, just like every other hormone. We just covered that it changes insulin and glucagon levels. We also just said that it slows down the gut, and it does THAT in multiple ways too. It’s easy to boil it down and just say that it causes you to eat less. The problem when you do that, is that you miss all the other mechanisms whereby things can and will go wrong and permanently alter the lives of millions of people around the world. It’s not a good idea to minimize it. So if it’s used inappropriately, it will throw the body off balance. A popular topic is how the brain connects to the gut. There’s a physical connection, via the vagus nerve. When a GLP-1 signal is sent from the gut, it tells the nerves to slow down. But sometimes, in very, very rare cases, the GI tract slows down so much, that it looks like KT’s case.

13:27 When KT was admitted into the hospital, She couldn’t take the weight loss medicine anymore because doctors didn’t even know at first she was taking it. But now that doctors do know she’s taking it, they tell her: No more doses for not only the time that she’s here, but, knowing that she has had this severe of a reaction to this medicine, it’s not a good idea to restart it later if it can be helped. That takes care of the underlying problem. But even when the gut is able to move things along again, the bezoar still needs to be taken care of. This can’t be handled without some help, meaning that KT is going to need some intervention. But what? Well, doctors could go in and mechanically disaggregate the bezoar. This would involve sticking a scope down her throat and swirling it around. But this can be risky because it’s not the same as using that scope to take a look. You have

14:15 to swirl it around to break it up. And control isn’t 100% precise. So there’s a chance of damaging any part of the GI tract in contact with the scope. They could do surgery to remove it. But, this isn’t a complicated bezoar. Like, if it was a hairball, you actually can’t use a scope to take that out, because you’ll just pull on just more hairs, especially if it’s a big one. It could be hard to recover from that too. She might get an infection afterwards. That could cause massive problems also. So doctors elected to not do surgery. But something that’s easy for them to do is to try to chemically dissolve it. This would prevent any direct, physical damage that could happen. It could also eliminate any recovery time needed post treatment. This would be a nontoxic chemical, abundantly available. And a perfect “chemical” that fits all this criteria,

15:03 is… carbonated soda. Diet in her case because she did have blood sugar problems. The fizzy carbonation of the drink can mobilize stomach contents. The stretch of gastric muscle from not only the liquid but also the carbon dioxide will help stimulate contractions to help get things moving along. Both Coca Cola and Pepsi were originally formulated by pharmacists, maybe for slightly different reasons, but at least in the late 1800s, they did find that the fizzy drinks were in fact able to help with some digestive issues. In one way, we’ve come very far with our current GI therapies, but yet in another way, the classics still can work, at the right time, for the right patient, of whom in this case, is KT. Doctors gave her 3 Liters of diet soda to drink over 12 hours. It’s ok,

15:51 it’s in the hospital so there’s people watching. The first day, she didn’t feel well. She couldn’t finish it. But on the second day, when she drank even more, she suddenly felt a tugging in her stomach. And this was followed by the absolute largest bowel movement of her entire life. Both the discontinuation of the weight loss medicine, which stopped her gastroparesis, and the chemical dissolution and gaseous disaggregation of her bezoar appear to have been the right treatment at the right time, as she was able to make a full recovery. KT’s case describes the consequences of gastroparesis in the setting of someone taking their friend’s medicine. Didn’t see a doctor about it. Didn’t get a prescription. But in the partial gut paralysis, she also had biliary tract dilation because of the bezoar. Luckily she didn’t have a gallstone; this weight loss medicine has been known to cause those too.

16:40 But this area of the gut can spawn some serious medical emergencies, just like in the case for: JC is a 34 year old man, presenting to the emergency room with abdominal pain radiating to his back. For the last 4 hours, green liquid was coming up from his stomach. He felt like someone had plunged a sharp object directly into his upper back. His stomach would burn everytime the hurt flared up. And all of this had started days ago. JC had recently heard his neighbor, and some of his friends, started taking weight loss medicine. At first, he didn’t think anything more of it. Their business. But one morning he looked in the mirror and wasn’t super happy with what he saw. He never quite got the results that he thought he would get at the gym, so it was time for him to tighten things up, he thought. After reading online, JC found out that he could find a prescriber on the internet,

17:27 who could get him weight loss medicine, if he was willing to pay up. He was quickly determined eligible, and was able to pick it up at the local pharmacy, and he started taking it. And he was feeling great. It was a little slow to start. He was able to live his normal life and everytime he’d step onto the scale, he saw progress. But things started happening. His mouth would get dry. He’d pour himself some water, but, he’d realize, he wouldn’t drink it. He thought maybe it was subconscious, and that maybe he just needed to put in some effort into drinking it, but even when he tried, he just didn’t want to. And then the water started tasting metallic. He tried some other drinks. Some days they tasted better than others. And he continued taking the weight loss medicine. But one evening, JC was sleeping. Suddenly, a sharp pain woke him up. And no matter how much he tried different positions laying down in bed, it wouldn’t go away. During the day,

18:15 he couldn’t get anything done, because of how much it hurt. He tried sleeping it off. But the pain was horrible. Even just smelling food would make him feel like he was going to throw up. In a fit of blinding pain, he felt like he was getting blood-eagled as he calls for 911 and he’s brought to the emergency room where we are now. In the emergency room, JC threw up on the nurse’s shoes. His breathing was stressed and he said that his abdominal pain radiated to his back, like someone had taken a crowbar and started prying it apart. A blood test finds that JC hyperlipasemia. Hyper meaning high. Lip from Greek referring to lipids or fats. -ase referring to an enzyme that breaks things down, like LactASE to breakdown lactose in milk, and -emia meaning presence in blood. High fat degrading enzyme, presence in blood.

19:05 Lipase comes from the pancreas. It’s released after we eat a meal. It’s secreted into the small intestines via the pancreatic duct, which joins the Common Bile Duct, where the gallbladder and liver release bile, done this way to optimize digestion and absorption of fats into the body. Lipase is only supposed to go in here. If it’s in the blood, then it means the pancreas is leaking it out. But the problem is, because it digests fat, and the pancreas is partially made of fat, and it’s leaking out, contacting parts of the pancreas that it shouldn’t be contacting, then, it means that JC’s pancreas is digesting itself. True to my message to you, that diet and exercise should always be front of mind in context of weight loss, CookUnity is a great option for getting started

19:50 on the right track for food choices. They’re the sponsor of this video. They just sponsored this spot, they had no say in me talking about GLP1. CookUnity is a chef collective that gets you restaurant quality meals by award-winning chefs delivered fresh to your door. Every week, I choose a couple of meals. The system also knows what I have really enjoyed and can make informed decisions for me. And delivered to my door is a whole week’s worth of lunch for me. And this helps me stay on track with what I eat. These meals are amazing and there’s a huge variety. Let me show you some of my favorites. Mexican Pork Bowl with Herby Green Rice and Mayan Sauce by Chef Ruben Garcia. The pork is juicy and the sauce when mixed with the rice is amazing. The flavors are incredibly unique. And take for example this Greek Style Chicken Gyro Pita Wrap with Handmade Tzatziki by Chef Cedric Nicolas. With every bite, there’s a perfect mix of spices, brought together by

20:37 pita bread that’s mixed with this wonderful tzatziki. It’s nutritionally very good. CookUnity is offering everyone watching this video 50% off their first order— click the link in the description below and use my code CHUBBY50 to try it out! Link in the description with code CHUBBY50. I highly recommend it! JC has acute pancreatitis. -ITIS meaning an inflammation of the pancreas, because something happened to it, enzymes started leaking out of it, and now it’s starting to digest itself. Acute meaning this is all happening suddenly. But why is this happening? This part about “weight loss medicine” sometimes is either forgotten or just isn’t known in the first place. It was originally a diabetes medicine. It wasn’t seriously being considered for weight loss at first. Because patients weren’t losing that much weight on the original versions. It was at most,

21:26 a couple of pounds at the cost of possible serious side effects like pancreatitis. One thing that we’ve known since the 1980s, is that GLP-1, can increase pancreatic cell proliferation. If the cells become too numerous, OR, if they become too big.. that’s going to squeeze ducts. This can block outflow. This can prevent lipase from draining out of the pancreas. The subsequent backup can cause it to linger at first. Then, to overflow. And then, digest the pancreas itself, as it flows out into JC’s blood, causing his horrible abdominal pain, and his hyperlipasemia. One part of GLP-1 discovery was from how it Delays Gastric Emptying. And another part of the discovery, was from the pancreas, in what was happening to JC.

22:12 In 1990, Dr John Eng at the Veterans Administration hospital in the Bronx, was interested in recent National Institutes of Health research that demonstrated that snake and lizard venom caused pancreas enlargement. Why did the venom do this? Of particular note, was the Gila Monster. However, one thing that was realized, was that Gila monster venom samples, contained its saliva. The Gila Monster is able to slow down its metabolism and maintain constant blood sugar levels after long periods of not eating. If the “venom” causes pancreas enlargement, and the pancreas makes insulin, which creates an environment of maintained blood sugar levels, well, something might be in here that’s involved with insulin. But the Gila monster doesn’t envenomate itself. And given that its saliva is in the venom samples,

23:01 and that saliva makes its way through the GI tract of which the PANCREAS is part of, then, what is in that saliva that connects with pancreas and insulin? When Dr Eng took a closer look at the Gila monster saliva, he found something called exendin. But he noticed something. In 1983, we still weren’t able to sequence whole genomes like we are today. But based on reasoning, and some genes that we already knew about in humans, scientists deduced the structure of something made by the pancreas called proglucagon. This is the precursor to glucagon in the body. But this predicted structure also indicated that proglucagon gets cut up into multiple different things. These all looked like glucagon. They’re from the same place as glucagon. But they weren’t

23:48 glucagon. And as a result, 2 of these “extras” were named Glucagon-Like Peptide 1 and 2. And when scientists knew what they were looking for, they discovered that their prediction was correct. It’s just that Glucagon Like Peptide only LOOKED like Glucagon. It didn’t behave like glucagon. When Dr Eng looked at exendin from the Gila monster saliva, he noticed that it looked like human Glucagon-like Peptide. And it appeared that its function was similar too. GLP1 isnt always floating around in our blood. Our bodies release it after we eat. But its signal is very powerful. So, our body wants to get rid of it. We have a built-in process that eliminates GLP1 in 2 minutes. The difference is, when exendin is in the human body, it does what GLP1 does,

24:37 but it’s different enough that the human process, cant break it down fast enough. It hangs around the body for hours, continuously sending all the signals that GLP1 does. If Gila monsters can slow down their metabolism and maintain blood sugar levels during long periods of not eating, because is exendin is in their saliva. And exendin sends the GLP1 signal to regulate blood sugar, and slow down metabolism, while lasting longer than GLP1 does, then, is it possible to give humans exendin as a medicine for type 2 diabetes? Type 2 is the diabetes that happens when one becomes insulin resistant. That is, after someone eats, insulin’s released, but the body doesn’t respond to it, and blood sugar always stays high, unless a medicine is given. Type 1 is

25:25 where the body can’t make insulin because the pancreas is damaged. And the answer is yes. We did it, in 2005. When we first studied it, it showed some mild effect on weight loss. But something that we did know, was that it COULD slow down the GI tract. That’s what it’s doing in Gila Monsters because this was intended to slow down its metabolism during times of fasting. And potentially, but not commonly, it could change the pancreas, bringing us back to JC. In the hospital, JC was started on IV fluids. He was dehydrated because he couldn’t keep any water down. Medicines were given for his pain, and everything seemed to be going OK. But only for a short time. When body parts appear to be damaged, the immune system reacts. This is to protect you.

26:11 But the problem is, sometimes the immune system overreacts. And it does that overreaction, when it shouldn’t be reacting in the first place. JC’s pancreas digesting itself is body part damage, so the immune system is there trying to protect him from that damage. But when inflammation, pancreat-ITIS, happens, the area can start to swell with fluid. And in JC, where his pancreas was supposed to be, is starting to swell with fluid. Usually in a 34 year old man with no diagnosed past medical history, this kind of pancreatitis resolves itself. The medical team elects to watch and wait, because even though his abdomen is swelling with fluid, doing surgery and cutting him open could be doing more harm than good. Even if the image looks scary, the body can and will, heal itself.

26:59 But one thing that they do find, is that despite stopping the weight loss medicine when JC was admitted into the hospital, the food in his GI tract, still hasn’t moved at all. This gastric stasis, also happened to KT. This slowdown, AND the pancreas effects were how the medicine was discovered. If we knew all of this, why did we turn this into a medicine? Well, the benefit outweighed the risk. For diabetes, this was originally an add on therapy. Eventually it became monotherapy. That is giving it by itself to lower blood sugar. But one more innovation would turn it into weight loss medicine. This same innovation is also partly responsible for why American “insulin” prices became so high. And actually we already touched upon it.

27:49 Before the 1980s, insulin used to be beef and pork insulin. That is, we used to take the pancreas from pigs and cows that were already taken for meat, and grind them up, purify it, and extract insulin from it, and let patients inject that. The problem is, people would become allergic. And they would switch. Back and forth for decades. And eventually, they’d just have to deal with the allergy. And even worse, to make 1 pound of insulin required 8,000 pounds of pancreas from 23,500 animals. And in 1978, the United States needed at least 56 million animals just for the production of insulin that year. We’ve only gotten more prevalent diabetes since. Scientists had an idea. Insulin is a chain of amino acids. And our DNA

28:37 sequence is the code that enables us to produce those amino acid chains. Pork insulin differs from human insulin by one amino acid. Beef differers by 3. But, if living organisms all have DNA, and DNA makes amino acid chains, could we engineer a genetically modified organism to make human insulin? Using E. coli bacteria, scientists were able to manipulate and isolate specific DNA fragments arranged in a way for those bacteria to produce human insulin. Engineered strains of bacteria were grown, placed in conditions favorable for them to produce pure human insulin. No more allergies. No more grinding up animal pancreases. And full control over how much insulin can be produced. And this technology changed everything.

29:25 Researchers noticed that if the amino acid sequence of a hormone was just slightly different, that hormone could last longer. Or it could last shorter. Or it could have a stronger signal. Or a weaker one. Just like how Dr Eng found out exendin behaved like GLP1, but lasted for hours instead of minutes. And now that insulin can be made with the exact sequence we’re looking for, then, it means we can also make custom versions of it, that behave in different ways. If we change some of these amino acids, we get a long-lasting insulin. Change these and make a short-acting one. And everytime we make one of these, it’s a new medicine. These act like insulin, but the dose is going to be different. Timing will be different. Give too much fast acting insulin, the patient could have life threatening hypoglycemia, low sugar presence in blood, very quickly. Give too much slow acting insulin in the daytime,

30:14 the patient might forget and wake up dizzy, fall down and crack open their head at nighttime. And you can’t use slow acting insulin by itself to treat diabetic attacks. And in the hospital or nursing home, the nurses don’t have to give insulin all the time and watch blood sugar like a hawk when it’s not all regular human insulin and you just give the slow acting one. So if it’s a new medicine, then it means it has to be tested and tried in humans again. And theres no guarantee that it works how we think it will, or that it doesn’t cause new side effects. And therefore, as a new medicine, it’s given a new patent, which means in America, it’s charged at a premium, explaining ONE REASON why “insulin” prices were out of control at one point. But this principle of changing amino acids, was done to exendin. It’s an important medicine,

31:02 but it wasn’t a good one. Gila monster bites are painful. Toxin and saliva are present. That might be why, exendin causes bruising, swelling and lumps where it’s injected. And patients had to inject it twice daily. Most people don’t get to that all the time. Making a custom version, could eliminate injection site reactions. It can be made to once daily injection. And maybe, you can engineer it to send a stronger GLP1 signal, selective for some parts moreso than others. And this is how it became weight loss medicine. One GLP1 derivative, created for diabetes was made to be given once daily, not twice. In the human trial, it was found to control blood sugar better than medicines of that time. But more importantly, this particular one,

31:48 was found to cause patients to lose an appreciable amount of weight in a long term followup in that series of studies. This realization changed that entire company. They ran human trials and found that a higher daily dose does cause humans to lose more weight. And they rebranded that higher dose as the first weight loss medicine. The first one that isn’t directly psychoactive to limit appetite, because those were the kinds of medicines that were predominant before this. And as they kept changing the amino acid sequence of GLP1, they converged onto the current formulations. Lower dose. Once weekly injection. Oral tablet. Competing on the amount of weight lost. Demonstrated to be safe and effective in people who need it, AND who can get the proper care. It’s just that when it’s scaled up to hundreds of millions of people worldwide,

32:35 you can find things that happen in extremes, just like in JC’s case. A few days pass, things seemed to be holding steady, JC didn’t need surgery, and he’s probably ready to go home, they thought. The medical team gets ready to discharge him from the hospital. Everything seems to be great. But as the hours pass, JC starts to get chills. He starts running a fever. His blood pressure starts to drop. His heart tries to keep up by pumping harder and faster. But it’s not enough. Another CT scan finds that gas is now in the space where the fluid was swelling. The stomach and the intestines have air in them, but they’re usually closed off so their contents don’t leak in to the abdomen, so if JC’s stomach isn’t punctured, then where is this gas be coming from? A blood test finds that not only are JC’s liver and kidneys shutting down now, but that he now

33:25 has an infection. If bacteria and fungus floating around in the abdomen, outside of the stomach, can produce gas, then it means that fluid buildup from his inflamed pancreas, is now infected. But it doesn’t just stop there. Whatever is infecting him, has now spilled in to his blood. The immune system detects this and tries to react again by dilating the body’s blood vessels. But this drops the blood pressure. Adequate oxygen can’t get to organs like the liver and the kidneys, as they start to shut down. JC comes in and out of conscious. Limited oxygen gets to his brain. All of this happening from pancreatitis in JC, that came from a weight loss medicine accident. When we look at KT and JC’s case, if you listened carefully, you will have picked up one little detail each. KT took prescription pain killers. It wasn’t a lot. But in chronic misuse,

34:17 they can cause GI side effects. Is it possible that these together, added with the weight loss medicine to create an additive or multiplicative effect? It’s not impossible. However, just know that hundreds of millions of people who are taking GLP1s around the world, some of them are going to be taking prescription pain killers. And many of them don’t get this degree of gastric stasis to the point of an obstructive bezoar. Next, JC had a drink. This amount doesn’t cause pancreatitis, and we know for JC it definitely doesn’t because that was a fairly regular amount for him. Despite knowing that these hormones can make pancreases larger, there hasn’t been an appreciable signal in hundreds of millions of people who have taken it, whereby their pancreases become abnormally

35:03 large. That doesn’t negate edge cases, but data tells us it doesn’t happen to the majority. Now I have to be clear here. Every time I describe 2 things together that cause one problem, some folks want to adamantly blame 1 single thing. Guess what, in the hospital, it can be more than a hundred different things causing 1 problem. So, let me say this again: these individual things alone each did not cause these patients’ problems. The prescription painkillers alone, did not cause her problem. She did not take that many. A single beer did not cause JC’s problem. How many people are on this medicine and have a beer. How many people take this medicine and need painkillers? I’ll give you the answer right now it’s in the millions. And not millions of people are having the same cases as these 2 patients. When combined with weight loss medicine,

35:50 you have to exercise caution. Everyone is going to have additional factors. You don’t wake up in the morning and only take weight loss medicine and cease to exist for the entire time until your next dose. There’s many things happening all at once when you take this medicine. Everything that you choose to add to your life, or you even need to add, will add more complexity and there will be some interactions when you’re looking at hundreds of millions of lives. So the most important take away that I want you to have from me, is, if you don’t NEED to take this, don’t take it. One of the principles of losing weight, is to always have room to adjust. Let me give you an example for this: So say you give yourself 4 months to lose some weight by diet and exercise. Your first 2 to 3 weeks should actually be really easy. You’re slowly starting to exercise

36:37 more often. And you have a set limit of calculated food intake. As your body adjusts to that, you’ll notice that the progress will start to stall. Then you can slowly add another day of exercise that week. And then the week after, have a little less at just 1 meal. And over the weeks as you keep adjusting, the final weeks can get a little bit lean because of all the accumulated changes. If someone does go on this medicine, and they had those other options available as diet and exercise but they didnt choose those, there’s suddenly a lot less room to adjust. They just dumped everything into this one position. It’s harder to maneuver now. And yes there’s going to be progress, but, where do you go after that? We know that people do rebound and gain weight back if they stop the medicine. But by the time that they do that, if they’re not careful,

37:23 hormones will be out of balance for extended periods of time, and even, may never quite be the same as a time before. Does that weight gain rebound happen with diet and exercise? It does. However, the other point to those, in able bodied people, is to build actionable habits. So these weight loss medicines have multiple mechanisms of how they work. They send signals from the gut to the brain to Delay Gastric Emptying. You feel fuller for longer. They stimulate insulin release, and inhibit glucagon release. They change hunger hormones. They change digestive hormones. You want to eat less. All of this is in line with how we found it: A lizard is able to slow down its metabolism during times where it doesn’t eat for months, because of a hormone in its saliva. And we’ve transported that into humans, with similar effect,

38:12 but for a different purpose. But we have to be careful, because this is hijacking one part of our bodies, whereas for the Gila Monster, this is built in. We’re not lizards. At least I don’t think some of us are. And so we need to exercise caution for when you NEED to use it. The last thing I want to say about these medicines is that there is way too much noise out there about these. Topics get brought up online that aren’t even in the conversation that we have about this in medicine. Others grossly simplify it. And in more the sophisticated cases, some of the claims are mostly right, but it’s that slight amount that isn’t right that screws you over and scrambles your mind. Many of the confirmed benefits of these medicines are centered around straight weight loss. The heart attack and stroke risk reduction. The treatment of nonalcoholic fatty liver disease. So if you do that weight loss without the medicine,

39:02 you get a lot of these benefits, because they also come from a reduction primarily in visceral adiposity. There’s the other potential benefits that we don’t really know about, like for alcohol use disorder. They’re being considered for research right now, but it’s not official treatment yet, and we don’t know much about it yet. But the way to keep your head clear amidst all of the noise is that every single prescription medicine out there is required by law to have a prescribing information insert, and this tells you officially everything that you need to know. What you find on here, should take precedence over anything you see about these medicines online. Or anything that you hear. Now, if you’re not in the medical field, don’t be stressed if you can’t understand everything this is saying. If you want a really easy time getting someone to explain this to you,

39:48 without an appointment, you can walk into any pharmacy and ask the pharmacist there questions at any time that it’s not too busy. I’ll get you started in understanding this. This black box about thyroid cancer. The few times that it was observed to happen in humans, it wasn’t clear it was because of this medicine. Notice that it says rodents. That warning’s been there since 2010. Since before this was weight loss medicine. Indication is a reason to use this medicine. If you NEED it, you’re indicated. If you DON’T need it, you’re NOT indicated. Contraindications are reasons to absolutely not take it. And it’s the Warnings and Precautions and the Adverse Reactions, which is a fancy phrase for side effects, that will tell you basically everything that you’ll need to know. Stuff outside of this, like things you hear from your neighbor who’s cousin’s friend’s wife’s boyfriend took this,

40:37 you can trust, if you want, but know you’d need to verify. Thousands of people in multiple departments, across multiple organizations vet every single word on these labels as their full time job. And if you could just sit in on one of these meetings, you’ll see that theres heated arguments about specific words, and how things are presented. Now if you’re taking compounded GLP1, there is no label for those. And what you could get, could vary widely. Use at your own risk, but ideally, if you do take this medicine, know what you’re taking, and make sure you’re getting regular care from a healthcare professional, ideally in person, and ideally, someone who cares and is a great fit for you. Use the package insert on the FDA approved version of the medicine to keep you grounded and your mind clear in the setting of excessive noise, and ask your physician or pharmacist if

41:26 theres anything you don’t understand. And what do you know. Gastroparesis, and acute pancreatitis listed in the warnings and precautions, bringing us back to JC. With supportive care and antibiotics. A diligent medical team who stayed on top of his treatment. Who discontinued his weight loss medicine. And who was able to counsel him better on lifestyle modifications and his goals. JC was able to make a full recovery. Thank you so much for watching up till this point. I know this was a lot of information but this is such an important topic because it impacts so many people. Exercise caution, and understand what this is, and understand yourself. And everything will be great. Take care of yourself. And be well.