Latest / Common Sense Health / GLP-1s (The Fat Jabs)
Transcript
- Stephen Thomas BSc. Hons: Hello. This one's going to be fun. We're going to talk about GLP-1s, you know, the fat loss jabs. So when you eat, your gut doesn't just absorb nutrients. It announces them. There's specialized endocrine cells in the intestine. They sense incoming nutrients, and they release hormones that prepare the body to handle what's coming next. Now, two of the key hormones here are called increments, GLP-1, which is glucagon-like peptide, and GIP, which is glucose dependent. Now their job broadly is to make eating metabolically efficient. More insulin when it's needed, less glucagon when it isn't, slower gastric emptying and crucially signals to the brain that influence appetite and satiety. Now the Increitin effect is an observation that oral glucose triggers a bigger insulin response than intravenous glucose at matched glucose levels because the gut hormones amplify the pancreatic In humans, that magnitude is typically described as roughly two to three fold higher insulin secretion with eating glucose rather than have it injected into the veins. So where do GLP-1 drugs come into this? Because we were talking about food and the natural response. Well, GLP-1 receptor agonists and the new dual agonists that also stimulate GIP receptors act like a long lasting pharmacological version of that meal driven signal. stimulate the receptors involved in insulin secretion in a glucose dependent manner, slow gastric emptying and strongly influence appetite and reward pathways in the brain. In plain terms, a short lived, food triggered signal is replaced by a sustained drug signal and for many people that dramatically changes just how easy it is to eat less. Now, you can call that the body being tricked. I think it is. But it's not that ridiculous, is it? But to be more precise, I would like to say it's the normal timing in context of signaling that's been altered. The drug signal can persist far beyond any mil, and it doesn't require actual nutrients arriving in the gut to switch on that same pathway. And that's exactly why these drugs are powerful. But it's also why the side effects deserve to be discussed properly as well, because The side effects of GLP-1s are often being understated. The weight loss claims, of course, are broadly real. There are caveats even with that, and it's those caveats that should be printed in a really big font size. Anyway, the story we're being sold goes something like this. Take this injection, lose weight, reduce your risk of everything from heart attacks to systemic inflammation. The version you tend to hear less often is also nearly everyone in the trial had side effects, some were serious and a non-trivial number of people stopped because they felt awful. That bit always seems to get whispered like, you know, that's a bit embarrassing, we won't add that bit or put people off. Well, yeah, right, weight loss, yes, tick, but weight loss is not automatically fat loss. One of the most undiscussed details is that the scales don't discriminate. They don't ask, hey, was that fat you lost? Was it muscle? Was it bone? They just clap politely as your number on the scale goes down. So in the semaglutide obesity trial that pretty much everyone quotes, the famous 68 week one, the average weight loss... in the drug group was dramatic compared with placebo. So roughly 15.3 kilograms versus 2.6 kilograms. Impressive. No question. But dig into the detail and it gets a little less like a miracle or more like, well, yeah, good, but hang on a minute. Because in the supplementary data, a large chunk of that weight loss wasn't fat. It was lean tissue, muscle and bone. The figure highlighted in the text is actually 39 % of total weight loss as lean mass in that analysis. So if you're thinking, but I thought that was a The fat loss drug we would talk about, you're not alone. But the marketing, yeah, that implies you're shrinking your waistline. But the biology says you may also be shrinking the very tissue that keeps you upright metabolically, and makes you less breakable when you trip over a dog toy at 2 a.m., bone and muscle. So it does reduce appetite, and that's doing a lot of work here. The party line is that these drugs reduce energy intake because they reduce appetite via brain effects. The key phrase though is often thought to result from. So a translation is we have a plausible explanation but it's not exactly a solved crime. What does seem clear is that for many people the effect is powerful. When the drug stops, the appetite often returns quickly. That should surprise absolutely no one. If you pharmacologically mute a signal and then remove the pharmacology, the signal tends to come back. know, biology is a bit crude like that. And here's the part that deserves far more honesty. The adverse events themselves may explain a meaningful portion of the appetite suppression. So when you feel nauseous, when you're vomiting, when your guts are staging a protest, know, eating becomes a lot less of an attraction, really. The side effects aren't a footnote. They are the mechanism for some people. In that same semiglutide trial, 90 % of participants on it 10 % had serious adverse events, 7 % stopped the drug because side effects were bad enough to discontinue. That was all they needed. So the most common problems were gastrointestinal, issues nausea 44 % diarrhea 32 % vomiting 25 % if a weight loss drug makes it hard to eat because your stomach is threatening to resign it's worth saying that bit out loud not presenting it as a quirky tummy bug vibe on the journey to your summer body now the add-on health claims you do need to proceed with caution because weight loss can improve many health markers and i think that's pretty much agreed but there's a difference between people lost weight and therefore some risks went down and this drug uniquely protects you from disease X, Y and Z. See the latter is where the nonsense multiplies. Once the drug is seen as a general health talisman every condition associated with obesity becomes a new headline. Asthma, sleep apnea, joint pain, you name it, weight loss does help those conditions. But that doesn't automatically mean a GLP-1 drug has some magical direct and the risk profile is being marketed like it's a mild inconvenience. Read the patient leaflets and the tone changes immediately. Suddenly it's less game changer and more. Please do not ignore the fact that your pancreas might struggle when it exists. You know, in the text the Wigovie patient information lists serious side effects, including diabetic retinopathy, complications, acute pancreatitis and kidney stones or even bladder stones alongside the very common cluster of nausea, vomiting, diarrhea, constipation, abdominal pain and fatigue. And then there's the kind of safety signal that makes you wonder what else is hiding in the supplementary information drawer. An Australian regulatory document is cited as indicating a five-fold increase in hip fracture risks in females with semiglutide asmpectra. a detail not prominently featured in many of the journal publications. Now, if you're going to prescribe something for indefinite use, bone and fracture risk isn't exactly a niche concern. It's central, particularly when we're simultaneously seeing substantial lean mass loss and bone loss. The solution to obesity is another narrative that ignores the actual problem. Behaviour, addiction, the food environment. A drug can suppress appetite. It cannot by itself fix why modern food hijacks people's behaviour. If someone uses a GLP-1 drug as a window, like a short opportunity to relearn some eating patterns, remove hyper-palatable trigger foods and build a sustainable routine, that is a coherent argument for that strategy. But that's not how the mainstream conversation is being framed. The framing is, take this and the problem goes away. The reality is more like, take this and you may temporarily silence the symptoms while the underlying drivers remain. You're not fixing your association with food basically. And then we get to the uncomfortable population level question. Even if individuals do lose weight, population obesity may not improve. The tech sites forecasting work showing obesity prevalence rising over time with projections remaining grim even in the era of GLP-1 uptake. Add to that the real world pattern of discontinuation many people stop with in a year and many restart because of weight regain. In other words, the drug works best while you're on it and stopping often means reversal. Now, add one more detail. If a large portion of the weight loss is lean mass and discontinuation leads to regain, that is more likely to be fat mass. You can see the outline of a very plausible disaster, a cycle that leaves some people metabolically worse off than when they started. So what is the sensible position? I'm not saying GLP-1s are evil and it's not GLP-1s are the cure, it's this. These drugs are powerful. That means they can be useful. It also means that the harms deserve to be discussed like adults, not like we're trying to keep the share price cheerful. If the dominant public narrative remains, astonishing benefits minus side effects, we'll repeat the pattern of every previous diet drug era. Initial hype, widespread use, preventing adverse events and then a slow, quiet retreat, leaving patients to deal with the consequences while everyone involved claims they were surprised. Because apparently nausea, vomiting, lean tissue loss, eye complications, pancreas problems and fracture risk are all just the cost of doing pharmacological business now. So hopefully you got the main point of that. We're looking at an effect that is mimicking what food does, but for a sustained amount of time. So a signal that is coming from nutrients, which is sort of momentary, you're going to have for a long, long time once you've taken that drug. Well, that's not natural, is it? Because you're getting all the signals of a big meal with no food whatsoever. I mean, that's the basis of it. And I think that underlying common sense of how this is working is enough. In another video, I will talk about the nuances of microdosing and why it's become popular with some people. But I just wanted to do a broad brush video to start off. And hopefully you enjoyed that. I look forward to you coming back for another video. Now, if you've got to the end of your enjoyed it please please consider to like share and subscribe and if you didn't enjoy it then please comment tell me how I could do things better and maybe I'll do a better video the next time around thanks very much for listening