Transcription
I need to admit something to you. When GLP1's for weight loss started to become big and everyone in medicine was talking about how they changed the obesity landscape, I was skeptical of the GLP1s.
Absolutely. Yes. Everybody thinks it's Ompic. It's not. It's something else.
I look around this room, I can't help but wonder, is Ozic right for me? I was a skeptic because this has happened before. Medicine tells us a compelling tale of a miracle drug. Then years later, we find out we didn't have the whole story and people ended up harmed.
However, the more I read about GLP1s and their newer generations, which we're going to talk about, drugs like Red or True Tide, my opinion has honestly shifted. In fact, my perspective has [music] leapfrogged from these drugs are being overhyped to maybe they're not being hyped enough or more precisely, maybe the benefits people are hyping are only the tip of the iceberg. And there's a bigger story here because the deeper I dug into the scientific literature, the more I realized these drugs are acting on so much more than weight. The brain, your heart, joints, liver, even your tongue.
For example, there are data suggesting GLP1s might directly reduce hallmarks of Alzheimer's disease completely independent of fat loss. Or when combining GLP-1s with other compounds, absolutely insane body recompositions like losing 50% body fat while gaining 6% lean mass. Yeah, this is possible because these aren't just obesity drugs. This is something much greater. [music]
So, in this video, I want you to give yourself permission to wonder, maybe everyone should be taking a GLP-1. Today, I'm going to demystify all of it for you with rigor, and I'll give you practical insights I guarantee you won't find elsewhere. Let's roll. These drugs are reshaping society at large. Muscle gain and fat loss at the same time. [music] Total fat mass in this study decreased by 50%. GLP1s might have protective effects on the brain. It's not just food noise. And now they have something that's truly liberating. Am I overvaluing benefits while overlooking potential harms?
All right. My ambitious goal with this video was to make the definitive GLP-1 guide a true one-stop shop answering basically every major question that people have about these drugs. I hope it achieves that aim. But to respect your time, we're going to emphasize the highlights, things people most want to know, things that are most misunderstood, and things people have absolutely no clue about. And I'll deliver on that. And if you want even more details, a true comprehensive guide can be found under our globally best-selling science newsletter, stay curious metabetism.com, linked below. And truly, if there's something I missed, drop a comment there and I'll expand on it. I want it to be the definitive resource for GLP1s, even if I have to write 50,000 words in that one post.
But with that, our road map. Honestly, I've stacked this to get better as we go. So stick around to the end for the best stuff. And there are some surprises throughout. So please no skipping. You kind of have to earn the end. Anyway, with that our road map. First, we're going to briefly talk about how GLP1s are already changing society just to frame our discussion. Then we'll get more practical. In part two, we're going to talk about common concerns. We'll separate real risks from internet hysteria covering muscle health, bone health, eye health, thyroid health. Then in part three, we're going to talk about the three GLP-1 generations. We're going to review how these drugs are being evolved and what most people don't know about the newest generation. Then in part four, we're going to talk about weight independent effects with special emphasis on the brain, my favorite part. In part five, we're going to talk about combination therapies designed to lose fat like a GLP-1 while preserving or even building functional muscle mass. Then in part six, we're going to do a quick rapidfire Q&A drawn from our Stay Curious metabolism community.
But with that, let's get to part one, the societal shift. Let me acknowledge something important. GLP1s are changing obesity, healthcare, and society itself. For example, semiglutide, our first generation GLP1, was approved for obesity in 2021. That's pretty recent. And since then, we've gotten new generations as fast as we're getting new iPhones.
The battery can't hold a charge, and the reception isn't VERY SHUT UP AND TAKE MY MONEY. And what have the population effects been? Well, the US obesity rate has honestly fallen from roughly 40% in 2022 to about 37% in 2025. To put that in perspective, that is 7.6 million fewer obese adults in America alone. An uptick is accelerating rapidly, too. In February of 2024, only about 5.8% of adults reported using GLP1s. By 2025, that figure had climbed to 12.4% over a doubling. And honestly, I'm guessing by 2028, a quarter of US adults will be on GLP-1s or some variation. And by the 2030s, most people will be on even stronger medications or combination therapies, which we're going to talk about later.
We've seen rippling effects, too, across society in the broader food economy. Because GLP1s don't just make you less hungry, they alter appetite and even taste preference. So, they're affecting the food industry itself, forcing it to adapt. Here's a fun fact. Your brain and even your tongue use GLP-1 to communicate. Your tongue actually secretes GLP-1 on nerves that go to your brain. So, we are changing the literal organs and tools we use to interact with food. This means industries will shift. Scratch that. Industries are shifting. Nestle, for example, has already launched an entire line of food products specifically targeted towards consumers of GLP1s.
And I want to frame this whole discussion we're about to have around these facts from the outset. Not as a matter of value judgment or ideology, but as a matter of reality. These drugs are reshaping society at large, medicine, people in our lives, like it or not.
That brings us to part two, common concerns. I want to start with a big one, muscle loss. The literature generally reports that somewhere between 25 and 40% of weight lost on GLP1s at a population level is classified as lean mass. And that sounds alarming. It sounds concerning, right? Are these drugs somehow causing excessive muscle loss compared to losing weight through only diet and lifestyle?
Now, there are two main explanations here with the second being the most interesting, but I need to talk about the first as well. The first is simply lifestyle context. People who lose weight primarily through lifestyle interventions, diet and exercise alone, probably as a population are more likely to resistance train and intentionally prioritize protein. And importantly, this muscle loss appears to be preventable.
Let me review the most impressive example of body recomposition I've ever seen on these GLP1s that blew my mind. It is drawn from the Stay Curious community. Actually, the member of the community is coincidentally named Nicholas N, not me.
That man is the impostor. And he started at 321 lbs in November of 2021. Initially he was just low carb dieting and fasting and he lost 61 lbs but then plateaued. Then because of medically diagnosed hypogonadism so low testosterone he was prescribed 200 milligrams per week of testosterone to just replace the hormone not to get super physiologic bodybuilder levels just to replace it to a normal baseline. And in conjunction with that, he took traceide, 200 gram of birkin daily, 10,000 steps per day, and resistance trained three to five times per week. The result was he lost 22 lb of further weight. But that's not the kicker. He dropped from 36% to 19% body fat while gaining 25.6 lb of lean mass over a year and a half.
Inconceivable. That's mind-blowing. And that is an extreme example. But the broader point remains even in the context of GLP-1 use substantial fat loss alongside muscle maintenance or in some cases muscle gain is absolutely possible when training protein and hormonal status and lifestyle are optimized. A reasonable rule of thumb place to start is resistance train at least three times per week and consume roughly 0.7 to 1 g of high quality protein per pound of lean mass while you're losing weight. and maybe consider some of the more advanced tips we'll hit later.
Stay curious side [singing] quest. Okay, I want to go on a quick stay curious side quest about muscle and to tease the brain health topic coming up later, but I was just reading a study in which researchers looked at identical twins and found that leg explosive power predicted better cognitive function and even larger brain volume later in life, which makes complete sense when you think about it since your muscles are effectively a hormone factory secreting things like irisin and BDNF to fuel the brain. Muscles are also important for good blood glucose control and insulin sensitivity, which are also important for the brain. So, get pumped about the brain health stuff coming later. Squat for your synapses. And if you want to fool around and have a little bit of fun with me for the next 90 seconds of this video, I want you to try to watch it while holding a horse stance. This is what we used to do as kids in martial arts class.
But if that's not reassuring enough, there's another level of nuance that most people are completely unaware of because the data are relatively new. Here's the deal. Lean mass and muscle mass are not the same thing. Most people think they are, but they aren't. Most of the studies that we refer to use DEXA scans. And while DEXA are useful, they're better than just a scale, it's still a relatively crude tool. DEXA lumps together muscle with other soft tissues, including the liver, into a single lean mass category.
And this picture, they're the same picture. And it also can't distinguish between metabolically active contractile muscle proteins versus less functional intracellular muscular substrates. But I realize that's a lot of mumbo jumbo. So let me back off and give you an analogy. DEXA scans are like weighing a suitcase without opening it. If the suitcase gets lighter, you don't know if you lost clothes or books or that cool carved ostrich egg you smuggled back from South Africa.
Let me take a look. Similarly, a drop in lean mass on a DEXA scan could reflect less muscle glycogen, water, even reduced liver size rather than a loss of actual functional muscle. In fact, 2026 research suggests that GLP-1s may preferentially reduce liver mass, which is not a bad thing, and non-essential muscle components without affecting the actual contractile machinery responsible for strength and physical function of muscle. In human studies, strength can be completely preserved despite reductions in measured lean mass, which might actually be referring to the case of the sneaky shrinking liver. That is a very important distinction. and to zoom out and make it as high level as I can. We've been miscategorizing some lean mass loss on GLP1s as muscle when in reality it was shrinking livers and other stuff you don't really need and in some cases your body might not even want. My take in a few words, concern about muscle loss on GLP1s has been wildly overblown.
Now let's quickly hit on some other concerns. Bone loss. Here's the deal. Rapid weight loss of any kind tends to reduce bone mass because your body is carrying less load on the skeleton. So body weight drops because the stimulus decreased. The body adapts. No biggie. That said, there are actually GLP-1 receptors in bone cells. And interestingly, the biology predicts there actually might be beneficial rather than harmful effects on GLP-1s once somebody is weight stable. GLP-1 signaling appears to stimulate osteoblasts. Think B for building. These are the cells that build bone. While inhibiting osteoclasts, think C for cutting down bone. These are the cells that break down bone. So through that combination, stimulating the bone building cells and inhibiting the bone breakdown cells. It is possible that individuals on GLP-1 once their weight stable could actually have improved bone health. For example, in rats with insulin resistance, GLP-1 treatment improved bone quality and strength. There's a bit more in the full letter below, but let's keep moving, which is also good for your bone health.
Now, I want to talk about vision loss. You may have heard alarming headlines linking GLP-1 drugs to blindness. Scary, right? Well, the primary concern stems from reports of a rare condition called, ready for jargon, non-arteritic anterior ischemic optic neuropathy or NAION for short. However, it's important to keep perspective here. Even the observational signal is very weak. For example, a 2026 systematic review found GLP-1 use was not significantly associated with this form of blindness. Now, there are small populations who might be at risk. I wouldn't rule it out completely. So, if if you have a reason to believe you have pre-existing retinal disease or diabetic eye disease, it's worth having a conversation with your doctor before starting GLP1 therapy. But stepping back and looking at the evidence holistically, I think the absolute risk here is likely very, very low. Something like half a percent in patients with diabetes over 5 years.
Next one, thyroid disease. One commonly discussed concern around GLP1s is thyroid cancer. Again, sounds really scary. Specifically, something called medullary thyroid carcinoma, a specific thyroid cancer. And the concern here originates primarily from rodent studies where GLP-1 drugs increased specific thyroid tumors. As a result, GLP-1s carry warnings specifically for individuals specifically for individuals with a personal or family history of medullary thyroid carcinoma or genetic syndromes that increase risk once called M2 syndrome. So if you don't have any history, personal or family of thyroid cancer or MEN2, this is unlikely to be a true concern. So overall, the human evidence so far is considerably more reassuring than fear-mongering headlines suggest. And if you know me, you know my bias is usually towards pharma skepticism. So me saying this, I hope carries some weight.
But that brings us to part three. The three generations of GLP-1 weight loss drug. Generation one, GLP-1 receptor agonists largely work by turning down the brain's hunger signal. These are drugs like Ozempic and Wegovy. Generation two are dual agonists. They hit not only GLP-1 but another hormonal axis called GIP. They still suppress appetite, but they also appear to directly influence fat cell physiology and fuel partitioning. For example, they seem to improve the body's ability to mobilize fat during fasting. I think about it at a high level as these dual agonists not only reduce hunger, but they make fat tissue more metabolically flexible. Those first two generations are FDA approved. And the new kit on the block which will get FDA approved is called tirzepatide. Sometimes called GLP3 although it doesn't hit the GLP1 pathway three times. It hits GLP1, GIP, and a third axis, the glucagon hormonal axis. And this one is particularly fascinating. The glucagon component does several things including increasing metabolic rate and energy expenditure. So in practice people report higher heart rates and more calorie burn on tirzepatide. And interestingly, in some cases, there can even be increased hunger, at least temporarily, while still having weight loss. I actually noted this myself in my own 1-month experiment.
So, I'm actually hungrier than usual at 10:00 a.m. I'm just going to eat what I want and see what happens. And tirzepatide is unequivocally the most powerful GLP-1 type drug yet. So again to zoom out when compared head-to-head over roughly a year with respect to weight loss, first generation GLP1s like semaglutide (Ozempic, Wegovy) they cause 10 to 15% body weight loss. Second generation, the dual agonists (tirzepatide, Zepbound) they cause around 20% body weight loss. And then the third generation tirzepatide with that additional glucagon component pushes weight loss towards about 24% over a year with slightly larger effects in women around 28.8%. Here's a little summary table for you. Pause and take a screenshot if you want. [singing]
Now, I do want to go on a quick stay curious side quest with you about the new kit on the block, tirzepatide. Specifically, since it's the newest, trendiest, and the least well-studied. There's some really interesting things people don't know about. First, like I said, tirzepatide increases metabolic rate, which means it increases resting heart rate. And yes, burning more calories is generally viewed as desirable in the context of obesity treatment. But increasing heart rate also increases cardiac load, which is considered a negative thing physiologically over the long term. Now this doesn't mean that tirzepatide is necessarily dangerous. But if you ask me what I'm most intellectually cautious about with this particular drug, it would probably be this question of long-term cardiovascular stress over decades of use. At present, we simply don't know. It's at the frontier of understanding.
Second, and also related to heart health, this really caught me off guard when I learned about it. Tirzepatide might lower LDL cholesterol and ApoB more potently than other GLP-1 drugs. I found this out when I personally experimented with tirzepatide for a month, just a month, even at a low dose, 1 to 2 milligrams for 4 weeks. I wanted to see what was going on under my metabolic hood. I wasn't trying to lose weight. You can check out this video for more. But what happened was my LDL and ApoB dropped substantially. Now, the larger drop came from something called ezetimibe, which you can learn about in this video. But the tirzepatide then further lowered my LDL and ApoB, which surprised me because physiologically I actually predicted the opposite. That observation led me to discover that the glucagon component that makes tirzepatide unique acts to lower something called PCSK9, which in turn lowers LDL and ApoB. It's a hidden lipid-lowering mechanism very few people are discussing and it's kind of wild if you think about it.
And then third, there's some speculation that tirzepatide might be muscle sparing, protects muscles. This remains inconsistent with the published clinical trial literature and is currently driven by mechanistic reasoning and anecdotal reports from the bodybuilding and biohacker community. There's no definitive evidence. However, there is at least a biological basis for this idea that I'll explain to you now. The glucagon component again that makes tirzepatide unique from other GLP1s can stimulate the release of a hormone called FGF-21. FGF-21 in turn can increase metabolic rate, so burning more calories, and could potentially help preserve muscle during weight loss. And the nuance here is that obesity is an FGF-21 resistant state. So if you pause and think about it, that could explain why published obesity trials have not shown a muscle sparing effect of tirzepatide specifically. Whereas experimental use in the biohacking and bodybuilding community where people aren't typically obese and are FGF-21 sensitive, they might be able to extract some muscle protecting effects from tirzepatide at present. That is a hypothesis. It is my hypothesis, but I think it's worthy of further investigation. You can let me know.
Now back to our main story. We're going to get to part four. The benefits of GLP-1s beyond weight loss. Now, what really shifted my perspective truly on GLP-1s had nothing to do with obesity itself. There are early promising signals suggesting GLP-1s might have protective effects on the brain on neurodegenerative diseases like Alzheimer's disease. For example, large population data sets find lower dementia rates among patients treated with GLP-1 drugs.
Now, obviously, I know what you're thinking, cuz you're smart. Interpreting these data is tricky because weight loss itself will improve metabolic health and other variables likely to benefit the brain. But there's actually reason to believe there are direct effects on the brain on brain health and even Alzheimer's prevention of GLP-1s. For example, researchers have noticed higher levels of GLP1s in the brain are linked to lower amyloid, a marker of Alzheimer's disease. Again, in human brains, you can see that relationship obviously here in both the line graph and the brain images. More red equals more amyloid. And on the brain on the left, that's the lower GLP1 brain. It has a lot more amyloid. Isn't that interesting?
Now, why might this be happening? Well, consider how amyloid forms in Alzheimer's disease. It starts with something called amyloid precursor protein. The name makes sense, right? And from there, the amyloid precursor protein can go down one of two broad pathways: a neuroprotective, non-amyloidogenic pathway and a neurotoxic, amyloid-producing pathway. And one enzyme in particular called BACE1 plays a critical role in pushing the amyloid precursor protein towards the amyloid toxic route. Fascinatingly, GLP1 inhibits activity of that enzyme that pushes the amyloid precursor protein towards the negative amyloid processing. So basically, GLP-1s can bias amyloid precursor protein towards a healthier, neuroprotective pathway.
But that's not all. GLP1s also improve insulin sensitivity in the brain. Now, why does that matter? Because impaired brain insulin signaling contributes to the activation of a protein, more jargon, GSK3 beta, which promotes the formation of the other hallmark of Alzheimer's disease, neurofibrillary tau tangles. So, GLP-1 induced insulin signaling improvements can block this pathway to potentially improve tau pathology in the brain as well.
So stepping back, I know I'm throwing a lot of jargon at you. Sorry, I'm a trained neuroscientist for my PhD. We have at least two, that's four, two plausible mechanisms by which GLP1s could directly influence Alzheimer's pathology. GLP-1 receptor agonists, they can decrease amyloid by inhibiting BACE1 activity. So you're skewing the amyloid precursor protein towards a healthier processing system. And they can decrease tau by inhibiting GSK3 beta. For neuroscience nerds, this is a mic drop moment. And honestly, as someone at high risk for Alzheimer's disease, I find this extraordinarily promising. I'm getting giddy talking about it. In fact, if there was one reason I personally would consider taking long-term low-dose GLP1 therapy despite not trying to lose weight, this would be it. I might even consider fattening up a bit just to do that. Joking, sort of.
And now to give you another example of the weight-independent benefit of GLP1s from the scientific literature, a 2026 study looked at something called osteoarthritis. This is a very common wear and tear arthritis characterized by cartilage breakdown, pain, stiffness, and reduced mobility. Now, obesity increases osteoarthritis risk because you're just carrying more body weight, which is loading the joints sometimes in an unhealthy way. But intriguingly, GLP-1s may be doing something much more than just causing reversal of obesity to improve osteoarthritis. Research suggests that GLP-1s might directly influence the cells responsible for regenerating cartilage in the joints. And remarkably, GLP-1 treatment has been associated with a thickening of cartilage in humans. So, it's a double whammy for joint health. Weight loss equals healthier joints and more mobility. And there are direct effects of GLP-1 on cartilage producing cells as well.
The bottom line here is GLP-1s are not just weight loss drugs. Beneath the surface, the bottom of the iceberg, GLP1s appear to be influencing metabolism throughout the body in ways that extend far beyond the scale and in a good way. It's just that weight loss is the most obvious visual manifestation.
Now, I want to zoom out and humble myself a little bit by asking the question we need to ask. What is the true risk-benefit analysis? Am I, are we getting swept up in peptide mania in the increasingly positive cultural conversations around GLP1s? Am I overvaluing benefits while overlooking potential harms? These are questions we need to ask. And if you know me, you know I'm generally a pharma skeptic. Even for highly studied, extremely common medications like statins, I do have serious concerns, which is not always a popular opinion. That said, we need to consider how these drugs work, their underlying metabolic effects, and their likely overall risk profile and benefits taken over the long term. And here, just being honest on my assessment of literature and mechanisms, I do have to admit, provided someone doesn't lose too much weight on a GLP1, my current view is the benefits of these drugs likely outweigh the risks for most people, even beyond weight loss. That is not a medical claim. And I'll be very clear here. I've taken zero dollars from the pharmaceutical industry. This is just my opinion. Take it for what it's worth.
With that said, let's now bring the discussion to the next level in part five, the future of fat loss and muscle gain. Because the most interesting part of the GLP-1 story comes from the frontier. Combination treatments like those combining GLP-1s with compounds that support muscle growth. In other words, these combination therapies help you lose fat while building muscle and sometimes a lot of it.
To frame this, let's zoom out and consider that evolutionarily, muscle is expensive. Your body absolutely has the capacity to build large amounts of muscle, but under normal conditions, that process is restrained by built-in biological breaks on muscle growth designed to conserve energy. Now, interestingly, some animals and humans have genetic mutations in which these breaks on muscle growth are broken, leading to low body fat and unbelievable musculature. This cow is not AI and we're learning how to mimic this now with small molecules in clinical trials. For example, two of the major breaks on muscle growth are called myostatin and activin A. So the logic is straightforward. If you block these breaks, if you break the break, you unleash muscle building potential and also fat loss.
So in monkey studies, animals taking these breakers combined with GLP-1 drugs, you can track the purple rhombuses here, exhibit massive fat loss along with increases in lean mass. Total fat mass in this study decreased by 50% while lean mass was increased by 6%. That is crazy. And that's not all. There are human data too. Early randomized control trial human data show similar signals. Over just eight weeks with one treatment, human participants gained roughly 3 kg, 6.6 lb of lean mass while losing 4 kg, 8.8 lb of fat mass after a single treatment. Muscle gain and fat loss at the same time in a matter of weeks.
Now, I know I'm excited. This field is still early and there are absolutely unanswered safety questions. But if these approaches prove safe and scalable, they may fundamentally change the future of body recomposition medicine. It's wild. But now I'm sure you're thinking what I'm thinking, which is this is really cool, but also bummer because these tools aren't accessible yet. Nick, you're being a tease. Fair enough. Guilty as charged.
But there are other compounds, lesser known but equally fascinating, that may produce similar biological effects without being injectables. Just to give you one example, a compound you won't have heard of called ATX304. You can read much more about it in this dedicated letter to ATX304, but here's the high-level overview. It's something called an AMPK activator. AMPK is one of the master regulators of energy metabolism in the body. And ATX304 effectively just helps pull fuel into muscles while simultaneously increasing fat burning and energy expenditure. The pre-clinical animal model data are impressive. For example, in one recent study, a 32-day treatment with ATX304 led to a 21% reduction in body weight, 100% of which came from fat. And what's more, again, in an animal study, when ATX304 was combined with GLP1s, there was a lot of fat mass loss with no reduction in lean mass. Again, link below for more. And I actually have some of this in my fridge. And when I used it, it lowered my fasting blood sugar by 6 milligrams per deciliter, which is pretty cool. That said, I haven't personally tried it in combination with GLP1s because I don't want to lose any more body fat. I actually think I went too far in my four-week tirzepatide experiment. Got a little crazy. That said, I have recommended ATX304 to two family members on GLP1s and they now swear by it. I'll share more information below. Not medical advice. I'm not saying anybody needs to try this. I'm just highlighting what's emerging right under people's noses. And within a few years, I'm pretty confident most people using GLP1s will be incorporating adjunctive therapies alongside them, like this one.
But that brings us to part six. We'll bring it home with some audience Q&A. Before we start that, quickly, I just want to give you a round of applause. Pat yourself on the back. You've stuck with this through to this point in time, which means you are committed to learning about your health and you can tolerate me rambling at you. So, kudos and thank you.
But with that, some questions. Zach asked, "What do you, Nick, think about the new oral GLP-1 orfor glybrron?" Well, first, I hate the name. Who the heck named that? It sounds like a Men in Black alien.
You guys get along. All right. But that aside, for those who haven't been following, orforglipron is a new oral non-peptide GLP-1. Weight loss appears to be broadly comparable to first-generation GLP-1 injectables like Ozempic with 11.2% body weight reduction over 72 weeks, alongside with improvements in metabolic markers. The real significance here is you can just pop the pill rather than giving yourself a poke. So, it's mostly an accessibility and preference thing.
Next question. Gabriella asked, "What about rebound weight gain if you come off a GLP-1?" Okay. If someone changes nothing about their lifestyle, starts a GLP-1, loses weight, and then abruptly stops it, they will typically regain the weight. However, this doesn't appear to represent some kind of permanent metabolic damage or a dependency created by the drug. It reflects just return to prior lifestyle patterns. Also, please consider GLP-1s might function as a catalyst for lifestyle change. If they're able to reduce food noise and allow someone to improve their lifestyle quality, make better dietary choices, establish healthier eating patterns, exercise more consistently, and improve their metabolic flexibility, then at some point someone might not need a GLP-1 or might be able to go down to a low maintenance dose. This is actually quite common. And also, there's growing interest in adjunctive therapies that might help prevent rebound weight gain after GLP-1 discontinuation. For example, that ATX304 we talked about before, at least in animal studies, it appears capable of preventing weight regain after stopping a GLP-1. That is just one example among many promising options.
Okay. Jen asks, "What about GLP-1 drugs for alcohol use disorder and other drugs of abuse?" Well, we know GLP-1 signaling reaches the brain, including regions involved in reward, craving, addiction. We also know there are actually genetic variants in GLP-1 receptors that have been associated with differences in things like alcohol self-administration and altered reward responses in the brain. So, it is not a stretch to think that GLP-1 drugs might influence alcohol use disorder, smoking, binge eating, and other compulsive behaviors. And increasingly, that appears to be the case. One of the most common reports from people taking GLP1s is not merely I eat less, but rather the food noise got quieter. But it's not just food noise, it's alcohol noise, nicotine noise. You get the idea. As a real quick aside and caution against misinterpretation, this does not mean you're losing your pleasure from these things, per se, because wanting and liking are very different circuits in the brain. So, this is primarily affecting the wanting pathway, not necessarily the liking pathway, which is honestly a great thing.
Okay, next question. Sam asks, "What about gastroparesis, also known as stomach paralysis?" I think this topic is often discussed in a confusing and alarmist way. First, we need to distinguish between two things. The intended mechanism of GLP1s versus true pathologic stomach paralysis, gastroparesis. GLP-1 drugs, let me be clear, are supposed to slow stomach emptying. That's part of how they work. True gastroparesis is different. That refers to severe dysfunction of stomach emptying causing things like nausea and vomiting. Severe gastroparesis remains relatively uncommon on GLP1s. The risk does increase when doses are escalated aggressively or you're on a very high dose or when people overeat when gastric emptying is slowed per to the intended mechanism. So tips: start on a low dose, then titrate up slowly and don't binge eat. If you are taking a very high dose of a GLP-1 and you smash a whole pizza out of habit, it's going to cause tummy troubles. No surprise.
Now, thank you again for sticking with me through this video. You are clearly committed to learning about your health and I love that. As my final remark, the reason I moved fairly quickly from being a skeptic to a relative fan admittedly is not because I have any conflicts of interest with pharma (I don't) or some personal need for these drugs. It's because I spend a lot of time immersed in both the scientific literature trying to stay current and I'm also seeing how these medications are affecting real people, loved ones in my life. People have explained it to me like they've been fighting an uphill battle inside for decades. And now they have a tool that is truly liberating, not a crutch, but an advantage in a world where our modern environments are conspiring to keep us fat and sick. So, what I see is a meaningful amount of liberation in a world that's basically booby-trapped by a toxic food environment. And beyond that, I see real promise for what might happen under our metabolic hoods. And I hope I convinced you of that today. And finally, if you want to see where humanity is headed next, check out this video. [music]