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People are running their own experiments with GLP-1s — with stunning results
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- [00:04]
A
This is in conversation from Apple News. I'm David Green in for Shamita besu. Today, the GLP1 experiment happening in real time.
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Millions of people in the US are
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taking GLP1 medications right now. An estimated 1 in 8 adults. You probably know these drugs by their brand names, Ozempic, Wegovy, Manjaro and Zepbound,
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just to name a few.
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GLP1 based drugs have been around for years and were originally intended for treating diabetes, but they exploded in use when researchers discovered they could cause significant weight loss and were approved for treating obesity. But people are now reporting improvements across a remarkably wide range of other conditions as well, from addiction to concussion symptoms to fertility, most of which have have yet to be formally studied.
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C
The landscape is changing so fast. There's new drugs coming on all the time and we're learning in real time what these drugs are doing.
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A
That is Julia Belous. She's a contributing opinion writer to the New York Times and co author of the book Food the Science of How Food Both Nourishes and Harms Us. Julia has been reporting on GLP1s for years, so I wanted to have her on the show to take stock of this moment. What has changed since these drugs became a cultural phenomenon, what the evidence shows and still cannot answer, and what all of it reveals about health science in America.
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B
So you've been covering GLP1s from kind of the moment that they broke into our consciousness. I wonder what you have seen change. Like, what do you think was the story then and how would you describe the story of these drugs now?
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C
Oh, there have been so many changes. I think one of the fascinating areas that has shifted is this explanation of how the drugs work. If you go back to the early days when these drugs kind of exploded from being used for diabetes to being used for weight loss and obesity, the general narrative was this idea that this is just a souped up version of a native hormone that we all produce for satiety. So GLP1 that our body produces in the gut gets released after a meal. It helps us feel full and stop eating. And we just in these medicines give people a really high dose of that satiety hormone. Therefore, that makes us feel fuller, faster, and we stop eating.
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B
We feel satiated, but we don't have to eat anymore.
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C
Exactly. Yeah. But it turns out that that's not how these drugs work. We're producing GLP1s in the gut, but we also produce it in the brain and to a lesser extent the pancreas. And the researchers studying it say, you know, it's not all that important physiologically. These are brain drugs. Right.
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B
So the narrative that people fell into, you're saying is that, oh, this just works with my digestive system to make me feel less hungry. And you're saying that's actually largely not true. It has much more to do with brain chemistry and how GLP1s interact with your brain. That's where we think the weight loss might be coming from and the eating less.
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C
Yes. Yeah. So a lot of what we know about GLP1s, we know a lot from clinical trials in humans, but we also know a lot of this modeling of how they work rodents. And that's true of the appetite system. Generally. A lot of what we know about appetite comes from animal studies. And so these studies of rodents where they knock out the receptors in the brain, the GLP one stop working for weight loss. And so it seems like they really need to reach into this GLP1 brain system to start getting that appetite reducing effect. I think that the other interesting bit of it in the last few years is we had Semaglutide, that was the first approved drug in the form of Wegovy. And now we have these other dual triple agonists that have come on the market or are coming on the market, and you're getting more and more weight loss with these newer GLP1s. So the numbers now with the newer versions that are in testing, you get close to the levels of weight loss that you get with bariatric surgery only.
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B
I mean, part of what we're seeing now in kind of the health fitness messaging is you should be okay with whatever body type you have. You can be have a large body type, small body type, and you're still healthy. Wouldn't that contradict the narrative that people are rushing to get these weight loss drugs because they want to get smaller?
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C
So this was, I think, what these drugs revealed, this quest for weight loss is a very long over a century. And you can trace it back even longer where people are trying to achieve a thinner, a smaller body, they're trying to lose weight. So humans have done jaw wiring, we've taken ingredients from explosives during World War II that sped up the metabolism and caused weight loss. We've taken tapeworm, injected ourselves with elements from horse urine, not to mention all of the fad diets that those of us growing up in the 80s and 90s remember very well. And that continued to this day. Right. So I think this desire for thinness is not to be underestimated. But we never had a Medicine that really worked, that wasn't dangerous, that worked at these levels to help people lose weight. And so I think on the one hand, there's now more of an appreciation that maybe there was all this. And there still is this discussion around willpower, right? And, you know, if you're overweight or you have obesity, you just need to buck up and stop eating all the cookies and whatever the thing is, and just white knuckle your way to weight loss. And suddenly you have this drug and people find all the quote, unquote willpower they never had just by taking a medication. And so I think there's more appreciation that our weight is our physiology interacting with our food environment. And some people have a much harder time than others. And when you take a medication, they can lose weight. So I think it helped people see that body size isn't a choice. At the same time, for the people who can access the drug, it is a choice. Right? And I think there is this pressure around looks. And so we're moving away from the medical conversation and talking more about this, like, cosmetic optimizing. And we're seeing people like, we're almost like back to the 90s where, you know, it's like thin maxing or whatever you want to call it, looks maxing, but like people getting thinner and thinner and wasting away and taking these drugs far away from any of these approved uses or medical reasons just to optimize their thinness. And I worry about, like, the pressures around that are just going to increase, right?
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B
I mean, we have 1 in 8 people in the United States taking GLP1s now. How much do we know about who those people are? Because it goes beyond people interested in losing weight. There are other health benefits that seem to be emerging that may or may not be backed by science. Like, what do you know about all these people?
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C
So I was very curious about that question. And we did this survey for my work with the New York Times, asking something like 2,000 members of the American public like, why are you using these drugs? What's the experience been like? And I went into that story thinking we would find a really negative. I don't know, there's all this data on how a lot of people discontinue using the drugs. They run into insurance barriers. I had talked to a lot of people who their insurance stops covering it. They have to cycle between different drugs. They become quite disillusioned about the amount of weight loss that they had. And I thought, this story isn't really being reported in the often triumphalist headlines about these drugs. So we do this survey and what comes back is, first of all, something like 65% of people said they'd want to stay on the drugs, and 63% said they'd stay on the drugs even if they stopped working for the condition for which the drugs were prescribed. Which just like blew me away. And so we started to dig into what's going on here and why are people like, you know, what are the benefits that people are uncovering while they're taking these drugs? And we found this astounding array of reasons that people want to stay on the drugs and surprising benefits they've had. So, like one woman, she had really severe post concussion syndrome after a car accident. And for like 10 years, her usual life was completely derailed. And she found some research on mice and on cell studies suggesting that the drugs might have benefit for this post concussion syndrome that she was suffering from. And she started on a GLP1. And within days her symptoms began to reverse. And out of all the things she tried, basically nothing worked. And now she's almost back to her usual life after like a 10 year chunk of losing her normal life. So I heard stories like that. I heard about people with irritable bowel syndrome who had nothing that worked for them. GLP1s helped. I heard from people like alopecia, people with different addictions, people with obviously, yeah, there were the weight loss, the diabetes, the cardiovascular disease, the liver and the kidney diseases. But there were also all these other uses that people were finding for these drugs. Long Covid symptoms. It was just this astonishing array of conditions, symptoms, and diseases that people were finding relief with. GLP1s, which is amazing.
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B
I mean, that's one of the reasons that you describe this as the great GLP1 experiment, because so many people are sort of experimenting on their own with these drugs. But how worrisome is that? I mean, has science caught up yet with a lot of these big questions, or people just sort of using these drugs and saying, wow, my IBS is better. Wow, I'm having fewer concussion symptoms. And stories are being shared and this thing is just exploding without science really catching up.
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C
So the science, I guess, was like 20 years ahead of where we are, in a sense, because researchers, I don't know, even 20, 30 years ago, they started to hypothesize about what these drugs could do for diabetes. And then, I don't know how many years ago, over a decade ago, the weight loss results started to come in. So we're catching up to that. But for this Multitude of other uses. This is where this is a population wide experiment on a scale we've never seen before. So someone told me a very high level official in the UK recently said, we've never had a drug that states have completely lost control over the way they've lost control over GLP1s. And I think that's true. It's that we have this frictionlessness in all these facets of our life now, the way we eat, the way we access like anything with so little friction. And I think the same is true for drugs like with the rise of telemedicine with the Internet. You can now order research compounds from China if you're interested. There's all these ways to access these medicines that we haven't had in the past and then you couple that with this demand, it's quite astonishing and it's absolutely an experiment happening in real time.
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Yeah.
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How accessible are these things? Like I have friends, I have family who have been able to just jump on the Internet like and telehealth their way into getting started, you know, without really having to have much communication about exactly what the goal is and whether or not there might be risk involved. Is this just the wild, wild west when it comes to accessing these things?
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C
Yeah. So the barriers to entry through telehealth are extremely low and not, not, I should say there's like a range of the barriers that companies put up, but there are companies where you just have to self report your BMI and it can be very easy to access the drugs if you, if you're willing to pay out of pocket and even if you're not willing to pay out of pocket. Patients have told me that providers will find ways to help patients gain access to the drugs, even if they're more like in this kind of recreational user camp, people who really need the drugs for diabetes or obesity or the other approved indications. You have the illicit and black market that is flourishing online for people who are interested in the research compounds that aren't yet approved. And there are also people who don't want to pay for even compounded or branded drugs. They're finding workarounds. So there's a gray and black market that we don't even have a good picture of and then just the official market itself is massive. So I think this is absolutely a Wild west moment.
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B
So how should we interpret these stories of people who say things like GLP1s have, have made me want alcohol less, have helped me with my anxiety, have helped me with my brain fog, have helped me with fertility. Like, should we believe these things if it's just anecdotal?
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C
I think that the experiences of patients are real. Like, I've talked to these patients, and a lot of the researchers and clinicians I interview are hearing from them as well. And people really feel that, yeah, they're drinking alcohol less. Or some of the patients I mentioned who have had these astonishing reversals of long Covid symptoms or whatever it is. But for a lot of these, the unapproved uses, we don't have the data yet. One of the researchers I talked to a lot, he said, you know, we don't know if it's like 2% of people with post concussion or Covid or arthritis or whatever the thing is that's gonna find relief or if it's like 80. Just don't know yet. So I think that that's the case with a lot of these more niche or fringe or unapproved uses, whatever you want to call them, for the addiction. There's a lot of question about whether those effects are gonna endure. So there's long been research showing that there are overlapping pathways in the brain for hunger and these other motivated behaviors. And what we know from, again, animal studies is that, yeah, when you make a rodent really hungry, you increase the risk of addictive behaviors. And so the question that a lot of the researchers I talk to have is once the weight loss happens and the hunger does come back, once your weight plateaus, whether these benefits that people are finding around addictive behaviors, whether they're gonna persist, that effect of the reduced hunger will wane as your weight plateaus. And so there's this question of whether that's gonna have some effect of relapse from the addictive behaviors, cause your hunger is gonna come. So we don't know whether those effects persist. And on the flip side, there's a lot of anecdotal evidence about people having they experience other changes around their reward system. So maybe they feel depressed. I've talked to patients who take SSRIs, and they start on GLP1s and their mood spirals. But I think there's just a lot we don't know about what the drugs are doing to reward pathways in the brain. And it's a system that's still very opaque in research. It's a system we're still learning about, and now we're interfering. So if you step back again, it's like a hormone that our body produces that at low levels doesn't seem to have a critical function. It's not like insulin, where you stop producing insulin and you can die. Right. With diabetes or growth hormone, you stop producing growth hormone during adolescence, you stop growing. This is a hormone that doesn't have these dramatic effects, and yet we administer it in these really high doses with the drugs and we get all these effects that we're just learning about. And I think the same is true for how it's interacting with our brain systems. And so the effects on addiction, these might pan out in longer term trials, but we don't really understand them fully. And some number of people might have effects going the other way. Maybe their moods aren't improved, their moods are worsened or whatever it is, or their anxiousness is increased. These people exist too, and it would be great to put numbers on this.
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B
Well, without numbers, I mean, it sounds like there are a lot of unknowns, particularly about the long term effects of this drug. And there are risks. I mean, those two things are clear.
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C
Absolutely, yeah. So the common risks seem to be the gastrointestinal side effects. So the nausea, the vomiting, the diarrhea, those can be managed with like managing the doses that people get. And those can get better as people continue to take the drugs. But then there are these rare effects that we're learning about. So there are lawsuits against the companies. Damage to the ocular nerve, so eye damage for gastroparesis, this slowing of the movement of food through your stomach to your small intestine and it affects how nutrients are absorbed. And they've had quite severe manifestations of that. And those lawsuits are about how patients were inadequately warned about these potential known risks. And they seem to be rare. But I think there's still a lot we're learning. Right. There are people who have absolutely tremendous life changing benefit on these drugs. But as each of us individually take them with our different underlying risks and genetics and other diseases that we're grappling with, or other medicines that we're taking, these other risks and side effects, we're gonna learn more and more about them.
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Why aren't regulators doing more? I mean, just because they don't want to hold up something that's benefiting a lot of people.
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C
I don't think our system was designed for this moment. So the system, like the regulatory regime that we have for pharmaceuticals, it uses a quite formal approach to surveilling for side effects. So there's some monitoring that companies are required to do. There's some monitoring that happens through doctors doing these adverse events reports to the FDA about side effects that they're seeing in patients and so the monitoring happens through these more formal channels. But we don't have systems built for how these drugs are being both how they're being used in the post telehealth Internet age, let's say, or algorithmic Internet age. And we don't have ways to capture this more informal data people are sharing, although the companies are capturing it. And you know, they're very carefully monitoring social media and Reddit and seeing, you know, looking for new indications and the ways people are using and talking about these drugs to understand them. We don't have that equivalent through a nonprofit agency or a governmental agency doing that equivalent. There's a lot of fascinating studies that are happening through official scientific channels, but patients are running ahead with their own uses and all of that isn't really being captured in any formal way. Maybe these drugs can really help, but we want to be sure before thousands or millions of more people take them for these speculative uses, that they are actually helping. And for that we need to have better data.
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B
And I think about how we are seeing government regulators or government officials respond. I mean, we saw the Trump administration has just launched a Medicare pilot program that would cover GLP1 drugs for weight loss for the first time, giving access to patients who are 65 and older and younger, people with disabilities who have Medicare. Like, it seems like if anything, the government of the United States right now is saying we're seeing the benefits and we want to make sure that it's not just based on resources that people can access this.
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C
Yeah, I think we can expect the floodgates are going to continue to open before any of this is curtailed. Have the pill versions of GLP1s prices are coming down. There are still a lot of access issues. So I don't want to downplay those, especially for weight loss. So for diabetes, the coverage can be quite robust now through for sure, employer sponsored plans, but also through Medicare and Medicaid and for some of the other approved uses. But for weight loss, it's still a patchwork and people pay out of pocket or they hit a lot of barriers, and that's what's kind of helped this gray and black market flourish. So that seems to be a step in the right direction. But it is one of the ways that we're gonna see more and more people experimenting on these drugs. And so that's where I think there's gonna be more and more uncertainty when we get into this wider and wider population of people using it that aren't like the people in the clinical trials and they're Using it for things that we haven't even tested, potentially.
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B
You've said that the experiment in children is already underway. It's not like people have to wait until they're 21. I wonder what you, as a parent, think about.
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C
Yeah, so I covered childhood and adolescent obesity for some time, and this is an area where we didn't have many tools to help people. So there was bariatric surgery or there were, like, diets and exercise regimes that just didn't work for a lot of people. And now suddenly we have this drug that does seem to be helpful, even in kids. So there are now clinical trials in children as young as six with GLP1s, which I must say, like, I found quite shocking. But on the other hand, I'm talking to pediatricians and endocrinologists who are seeing cases of really severe diabetes and obesity diagnosed in children as young as six. And now we have this tool that seems in the clinical trials to deliver the same benefits that we're seeing in the adults. But I think the part that worries me and a lot of the researchers I spoke to is there's still a lot we don't know about what it means to be on a GLP1 during puberty, during these critical phases of growth and development. The clinical trials we have have only gone out to a year or 18 months. And if you start taking these at age 6, presumably you're gonna be taking these drugs for years or decades. And we don't have the data on what does it mean to blunt appetite during bone growth and brain development. And all of these body changes that are happening in puberty and adolescence. You know, it's something like there was a 600% increase in use in kids just in the last few years. The absolute numbers of children who are taking them are still quite small. It's something like 1% of kids and eligible kids and adolescents are using GLP1s. But again, just like the adult market, it's expected to grow. And I think in that time, there's a lot that we're gonna be learning in real time, just like the parallel experiment in adults, I guess.
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B
I wonder, just stepping back broadly, like, you've said that our regulatory system in the US Was not meant or built for this moment. You've written that we can't clinical trial our way out of this because it's become so prevalent. It's sort of a cultural reality. GLP1s seem like they are here to stay. If this is here to stay. Like, look, a decade from now, like, how prevalent do you expect these things to be in our country, in the United States and in our world? How common is this gonna become?
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If you go back to the beginning of our conversation where we said we're talking about these mainly as obesity and diabetes drugs, when you rewind a few years, and now we have all of these different approved uses. And like many more emerging indications that we might see in the coming years, in the diabetes trials, they also found this 20% reduction of cardiovascular risk, which is getting close. What statins deliver, right? So that's just the heart and then there's the kidney, the liver, the weight loss, the inflammation. So I think in 10 years, yeah, we might see many, many more indications. I think the thing that frightens me are these questions around long term use. And what does it mean to be on a GLP1 for decades? What does it mean to be on a GLP1 for decades, starting at age 6? And I think there's things that we can't know now and that we're gonna learn and I think some of them are gonna be potentially, I think some of them might be wonderful. Like we might learn that, you know, when you intervene earlier in obesity or when before people even arrive at obesity, we see a lot of diseases averted that we know were associated with that excess weight. But I hope that in 10 years we do have more data, we can understand more, you know, especially for all these other uses, when is a patient really gonna benefit and when is the risk gonna outweigh the benefit? And that's fundament medicine is about, right? It's about balancing risks and benefits. And right now, many of us are just operating in the dark. And I hope that in 10 years we're gonna have a much clearer picture of that risk and benefit profile for a much broader array of patients who want to take these drugs. But we're certainly. We don't seem to be there yet. We don't seem to be there yet.
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B
Julia, thank you so much. This is obviously something a lot of people are really interested in and I can't tell you how much I appreciate your wisdom and knowledge and telling us about what you've learned.
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C
Thanks so much for having me. It was a pleasure to be here.
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A
We'll include a link to Food Intelligence, the science of how food Both Nourishes and harms us by Julia Belous and Kevin hall on our Show Notes page. And every weekend you can find episodes of Apple News and Conversation in the Apple News app. Just tap on the audio tab, the little headphones phones at the bottom to find.