What we got wrong about GLP-1s

Search Engine is breaking its cowardly three-year silence on GLP-1s. We have been curious about them. We have been afraid of getting in trouble. We are no longer afraid. A conversation with Dr. Rachael Bedard about the many mistakes in how the media covered these drugs and what the research shows about their surprising effects. Dr. Bedard’s story on the rise of Ozempic https://nymag.com/intelligencer/article/ozempic-weight-loss-diet-drug-moral-panic.html Support the show! https://searchengine.supercast.com/

Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.

• 0:24PJ Vogt?

  Okay, so here's something. Our show's motto: No question too big, no question too small. But there's some questions that I have on this show avoided. I'll give you an example: GLP-1s. Search engine has barely acknowledged their existence, which is fine, except I read a lot about them, I think a lot about them, and in my private life, I talk a lot about them. But when they cannonballed into American culture, I had a lot of questions that I didn't want to ask in public. In 2022 and 2023, GLP-1s were just, for me, too hot a topic. Going online felt like walking into a crazy shootout in an old Western saloon, except instead of gunslingers, it was all fast draw scolders.

• 1:09PJ Vogt?

  There were scolders out there scolding celebrities for taking GLP-1s, but then they were getting scolded by other scolders for scolding celebrities? Some people got scolded because they were taking the drugs despite not being fat enough, scolded for wanting to lose 15 pounds. Rich people, of course, were getting scolded all over the place, accused of ripping GLP-1s out of the hands of the people who actually needed them. It was scolding mayhem. Meanwhile, offline, in real life, 20% of the people I knew just lost 15 to 40 pounds. They seemed happy, and I had questions. What did we really know about these drugs? Were they helping people the way they claimed to? What were the side effects? I had questions, but I hate getting scolded, so I kept my mouth shut.

• 1:53PJ Vogt?

  Meanwhile, in 2026, the scolders have moved on to other topics, topics I'll cover in 2029. But today, we can finally get some answers on these fascinating drugs, which it turns out are much weirder than we ever knew. So this week, we're going to talk to a doctor who's going to tell us the story of GLP-1s from her perspective, which is a very unique one, because she's a doctor to a particular patient population that we don't hear from much in the media, almost never, and who were very absent from the entire early discourse around these drugs.

• 2:31PJ Vogt?

  Can you say your name and what you do?

• 2:32Speaker 01

  Sure. I'm Rachel Bedard. I'm a physician and I'm a writer. I'm a contributing writer to New York Times Opinion. And as a doctor, I am an internist, and my subspecialties are geriatrics and palliative care. But I've had this sort of unusual career where for six years I was a physician on Micros Island, and I now work in a homeless clinic a couple days a week.

• 2:53PJ Vogt?

  Can you tell me about your work at that homeless clinic? Like, where's the clinic? What's it like? What's your work like?

• 2:59Speaker 01

  So the clinic is, it's a safety net clinic run by the city. The city has a network of these safety net clinics that are embedded in the public hospital system. And so my clinic is at Woodhull Hospital in Brooklyn. So the clinic's in the hospital, but it's an outpatient clinic. It's primary care. We serve people who are either unhoused or sort of in precarious housing situations. They were recently, you know, housed, or they are staying on friends' couches or something like that. But the majority of the people that we take care of are living in shelter or people who are sleeping on the streets. So we do sort of all of their primary care. That population has a very high rate of comorbid mental health issues, very high rate of comorbid addiction issues, but also

• 3:44Speaker 01

  is just very medically sick. So the majority of folks that I take care of are, have at least one chronic medical comorbidity, like high blood pressure, diabetes, or other diseases like that for which they're taking daily medications.

• 4:00PJ Vogt?

  I have like a bunch of questions in a bunch of different directions. One is, your work puts you, I think a lot of people who live in New York City, the weird thing about New York, maybe more than other places in America, is that it's both incredibly class stratified. You have like very elite, very wealthy people, and you have working people, and you have very poor people. But the people in those worlds don't always really run into each other, besides maybe on the subway, or literally on the street. You have this unusual life where you're moving between like, highly elite worlds, like the New York Times, and then working with populations that are so far removed from it. And I just wonder, the thing that I think so many people block out in their minds in order

• 4:44PJ Vogt?

  to just live in a city, you've chosen to give yourself a life where you can't? I'm just wondering what that's like.

• 4:51Speaker 01

  Yeah, so, you know, one thing I'll say about New York is although the rates of inequality here are astounding, there is, I think, actually more mixing in New York City than there is in a city like LA, for example, where people are always in their cars, right? Like, you are sort of interacting on the streets, and on the subways, et cetera, you know? And because of the density, people are just on top of each other much more. So, it doesn't feel, my life certainly feels extremely stratified, for lots of reasons. But I think I like living here because it feels as though humanity is in continuity with itself in a way that in some other parts of the country, or other very wealthy cities, you can be completely sort of cloistered off.

• 5:35Speaker 01

  That having been said, yes, my clinical work puts me in not just contact with, but I think just in extremely intimate relationship with people whose lives are really, really difficult in ways that my life has never been, and gives me a different sort of level of insight into what it's like to live in those circumstances.

• 5:54PJ Vogt?

  Right, you get this very, very intimate view into lives that are very different from your own.

• 5:59Speaker 01

  Right, like my patients, their experience of the weather is really different than my experience of the weather, because they are exposed to the elements in ways that I am not, with fewer ways to protect themselves. ranging from like they come to the clinic and they don't have a coat and they don't have gloves and it's really cold outside or it's really hot outside and they don't necessarily have a place to take cover from that, right? And so like, that's a really different way to be in a body in the same spaces that I'm in my body in, if that makes sense.

• 6:28PJ Vogt?

  Completely makes sense. How did you end up working at the homeless clinic?

• 6:34Speaker 01

  Well, I, so I had gone into medicine because I wanted to do sort of social medicine, like social justice work through medicine and it wasn't totally obvious how to do that. And I sort of very luckily by chance ended up in this job at a fellowship at Rikers where my job was to take care of older people who were incarcerated in the New York City jail system. And I loved that job so much.

• 7:01PJ Vogt?

  What does it look like day to day to be a doctor at Rikers?

• 7:05Speaker 01

  Rikers is a wild place because it is, it's an island, as you know.

• 7:09PJ Vogt?

  I've been once, actually.

• 7:10Speaker 01

  Oh, have you?

• 7:11PJ Vogt?

  Yeah, but you should describe it because I guess the median listener probably has not been.

• 7:15Speaker 01

  Yeah, so Rikers Island is an island off of Queens. It is connected to Queens via this long bridge. There are, there's security at the front of the bridge and on the other side, you can only drive on the island. You aren't allowed to walk on the island. It's sort of a fortress unto itself that the Department of Corrections for New York City runs and it is a complex of multiple jails that are all on this island, a bunch of different buildings. The buildings house people sort of in different sort of special populations. There's one for women, there's one for people who are sicker. There are ones for specialized mental health units and depending on the kind of medicine you practice, your day can look very different. So for the first few years that I worked there, I would basically print a list of everybody in the system who was older than sixty five.

• 8:00Speaker 01

  And I would go sort of try to find those people where they were and call them down to a clinic in that building. There's no freedom of movement in the New York City jail system, which means that every time a guy moves from one place to another, he has to be accompanied by an officer, like somebody has to come pick him up and unlock a door and take him out and bring him to you. So things move very slowly, like it's like being in the airport all the time, right? Or the emergency room. It's an incredibly sort of congested system that requires a huge amount of excess human contact. It's hard to have real privacy during clinical encounters because you're not actually sort of behind a truly closed door ever for safety reasons, but you can imagine that there's like a tension there with being able to provide care to people who are ambivalent about revealing themselves in that kind of environment, right?

• 8:44Speaker 01

  And so it is a clinical dynamic that's very much constrained by the security concerns of the system. And some of those security concerns are really well justified and some aren't. One of the first patients I had was with advanced cancer. I went to visit him while he was in the hospital incarcerated. There was a corrections officer sitting outside his room. He had told me he really liked Skittles, the patient. I brought Skittles. I had to open my bag and show the officer what was in my bag before I was allowed in the room. And I was too sort of junior to know that I should play it cool. And I said, I brought him Skittles. And the guy said, he's not allowed to have those. And I said, why? And he said, well, Skittles aren't on commissary.

• 9:26Speaker 01

  So he's not allowed to have things that aren't on commissary. That's like, obviously not a real security concern, right? That's just a rule.

• 9:33PJ Vogt?

  Yeah.

• 9:34Speaker 01

  And that's not a law, you know, even though the guy's saying it to me as in a uniform. And I was like, I'm going to give him the Skittles, you know? And you can imagine that that's hard to do and you have to have like a fair amount. You have to really feel empowered by the folks who run the healthcare side of things to be able to use your judgment like that. And I was super lucky in who my bosses were. And I was there for COVID. That was really wild. It made me feel incredibly bonded to a bunch of my colleagues and that my supervisors. And then I left at the beginning of 2022, quite burnt out. And a bunch of people who I worked with at Rikers moved on to work at Woodhall. And it was like, you know, like in Mad Men when they like remake the first, you know what I mean? They're like, they're like, season three, we're doing a new one.

• 10:18Speaker 01

  That's like the same guys. That was, that's what it was like. We'd like Mad Men'd up at Woodhall, which is a bunch of people who I loved working with at Rikers who are super mission driven. And so that's how I ended up there.

• 10:28PJ Vogt?

  And so you're there now, and it sounds like the thing that, I mean, there are many things in common, the people you're working with in common, but the other thing that sounds shared is that. I think when a layman thinks about a doctor, it's a person you go to and they figure out what's wrong with you and they give you medicine. And your experience of medical care is that oftentimes the job is as much about the social structures around people as just like treating their bodies. Because the things that are happening to their bodies and the social structures they're enmeshed in are so inseparable.

• 11:00Speaker 01

  Yes, although I would say that's truly true for any, any practice environment, any patient population.

• 11:06PJ Vogt?

  Really?

• 11:06Speaker 01

  It's just, yeah, it's just the challenges are really different and it's more visible, I think, with my patient population. But if you are paying out of pocket to see a concierge doctor, which in New York, there is like this incredible stratification and access to primary care. And one, at the high end, people are paying out of pocket to see concierge doctors, which means that they're paying some huge amount of money to have this person basically be on call to see them. And the dynamics of that relationship are totally determined by that payment model, by that person's socioeconomic status, by their access to be able to get care from other kinds of specialists, by their ability to like, you know, that doctor says, maybe you need a massage for this back pain and the person can pay for that massage, right?

• 11:47PJ Vogt?

  Right.

• 11:47Speaker 01

  It's sort of impossible to separate the body from the social.

• 11:52PJ Vogt?

  Yeah, yeah, yeah.

• 11:53Speaker 01

  And that's just particularly visible. And the social sort of circumstances for my patients are just so particularly crushing and throwing up obstacles. So they're being able to take care of their bodies the way that we would want them to, that a lot of what the doctor ends up doing is sort of negotiating with the world on behalf of my patients to get them things I think they need. The other thing I would say is that because my patient population, you know, health is socially determined up to a large degree. So like when you describe, like you go to the doctor, you say something's wrong with you and they give you a medicine, you're picturing going for like strep throat or something, right?

• 12:30PJ Vogt?

  Yeah.

• 12:30Speaker 01

  Or I have the flu and I want Tamiflu. Because that's the experience of people who aren't sick. But my patient population is sick, so they are living with illness all the time. And when they are coming to me, they're not coming necessarily with a new complaint so much as we are in this constant process of trying to modify their experience of illness. Medicines that they live with chronically.

• 12:51PJ Vogt?

  There's nothing about anything you've described where my underinformed stereotypical view of the world you're treating would say like, this is the pop culture sketch I have been given of Ozempic users. Can you tell me the first time you heard about GLP-1s? Like, when did they show up on your radar?

• 13:09Speaker 01

  Yes. So, right, exactly. And this is sort of my whole interest in these medicines to a large degree. So GLP-1s have been around for a really long time. Like, some version of GLP-1s have been around for almost 20 years. There were sort of like first generation GLP-1 medications that were only used for diabetics. So I've known about those medicines for a really long time. But the sort of GLP-1s class that is like the Ozempic generation and then everything that's followed really came on the radar like 2021, 2022. And I think the first time I sort of started paying attention to them was when I read about them in mainstream media,

• 13:49Speaker 01

  not in medical literature, because especially like those very early months, like they weren't accessible.

• 13:56PJ Vogt?

  Extremely expensive.

• 13:57Speaker 01

  And so there were sort of these studies that had been done, you know, by Novo Nordisk, suggesting like incredible results for diabetic patients. But there are lots of medicines of being invented all the time that are really promising, but that are too expensive and are just like not going to be on formulary for my patients that I don't actually know that much about. I think the way that I personally got really interested in the GLP-1s was I actually think that somebody I know who worked at Vogue called me and was like, what's the deal? You know, like everyone I know wants this medicine. Like, what's the deal with this medicine? And I was like, the diabetes drug? Like, I, you know, it was sort of not on my radar. And then I started to be interested in it as the weight loss effects became clear, well-known.

• 14:39Speaker 01

  And then the drugs started to be sought by a patient population that didn't have diabetes, but that wanted to use it for weight loss. And it became sort of this like cultural phenomenon. Like, I think 2022, 2023 is really when that happened. Like, 2023 is the year, to me, of the Ozempic first-person essay.

• 14:56PJ Vogt?

  Yes. 2022 was the year for me of people with Whispering about it.

• 15:00Speaker 01

  Right.

• 15:00PJ Vogt?

  Yeah.

• 15:01Speaker 01

  And then twenty twenty three was people being like, all right, I did it. I tried it.

• 15:03PJ Vogt?

  Yeah.

• 15:04Speaker 01

  Or like, or what does it mean for the body positivity movement that this is happening?

• 15:07PJ Vogt?

  Yeah.

• 15:07Speaker 01

  Whatever, like that, right? It was this really interesting thing where this diabetes medicine became this other thing. And at that point, like, really controversial, right?

• 15:15PJ Vogt?

  Yeah, it was a medicine that was also a discourse object.

• 15:17Speaker 01

  Right, exactly, exactly.

• 15:19PJ Vogt?

  And it like scrambled all these, there were so many relatively set battle lines and ideas about, as you said, like body positivity, and then you had this thing which just, it took this table and just like shook it really, really, really hard.

• 15:34Speaker 01

  Totally. And it was so unexpected, frankly, right? Because one of the sort of truisms up until this class of medicines was we didn't have a magic pill for weight loss, right? That there had been sort of all of these prior cultural moments like fen-phen in the nineties, where there had been like a hot discourse object medicine to help people magically shed pounds. Nothing prior to GLP-1s had been proven safe in a way that it could be sort of a sustained intervention for people. Nothing really worked that well. Whereas like all of a sudden people were taking Ozempic, they, it seemed safe. They were tolerating it okay. And they were losing fifteen pounds in five weeks. And that, it was just so unprecedented in its efficacy.

• 16:16Speaker 01

  Like, we hadn't had anything like that before. I mean, like, these drugs, by the end of twenty twenty three, we knew that they had an all-cause mortality benefit. Like, that's unbelievable as an outcome. Um, there are very few things in medicine where you can show that it prevents people from dying over a very short period of time of taking the drug. And this did that. And so like, it was really an incredible, from a medical perspective, it was super exciting. And at the same time, there was this like, weight loss, body image, yada yada discourse that was so totally divorced from the actual medical impacts of the drugs.

• 16:55PJ Vogt?

  This yada yada discourse Dr. Bedard's referring to, that's what I was referencing in the beginning of this episode. A season which yielded many essays from writers wondering out loud if these new drugs were just morally wrong. To Dr. Bedard, the problem with these pieces is that they rarely seriously engaged with a world beyond the writer, their social circle, and celebrities on Instagram.

• 17:18Speaker 01

  I was annoyed on a bunch of different levels. One thing is that it just highlighted how much cultural discourse about bodies, even illness, medicine, people's experience of their bodies, really almost never reflects the experience of people who are actually ill. So, you know, type 2 diabetes is like one of the most common chronic conditions that Americans live with. It's really, can be really terrible, right? Like, millions of people in this country have had a limb amputated because their diabetes was sufficiently bad that they had vascular complications where they stopped getting blood flow to a limb and they had to lose a leg, you know? That's really terrible.

• 18:00Speaker 01

  There are half a million people in the US who are on dialysis, which means that three times a week, they go for several hours and sit in a recliner, in a room full of people in recliners, hooked up to huge IV catheters that are exchanging their blood through this like, blood washing machine, dialysis machine. That's a wild way to live, right? I imagine if you had to do that. And those experiences are never reflected in first-person writing about illness in the mainstream media. They're almost never actually described, I think, in, you know, the publications that, like, I read, both for news and pleasure.

• 18:43Speaker 01

  Whereas, I'm 43, I think for as long as I can remember, I have been reading an essay a week about what it's like to be a white lady who doesn't feel great about her weight. That, that is a constant in my life through many changes in the world. And the idea that this breakthrough class of medications that had the potential to revolutionize, like, chronic disease, population health in the US, potentially changed the expected mortality for Americans, like, that it was all sort of being funneled into this same discourse and also processed using the same types of-

• 19:22Speaker 01

  Anxieties and neuroses that were sort of the themes that I've been reading about my whole life, like, was really annoying to me.

• 19:36PJ Vogt?

  To Dr. Bedard, what was annoying in 2023 was how the conversation about these drugs gave almost all of its oxygen to their cosmetic attributes. What did it mean for everybody's body image that thinness was now much easier to buy than it had been before? I can feel even now saying that sentence, the heat and excitement of all the arguments it provokes. But for Dr. Bedard, those arguments made her want to yell at the screen. Forget even for a second the cosmetic implications. GLP-1s were transforming the lives of some of her most vulnerable patients. She thought more of the oxygen in the conversation should have gone there, and that the discourse certainly should not have been so focused

• 20:19PJ Vogt?

  on the very particular lives of media elites. We're going to take a short break. When we come back, we are going to move away from discourse, away from the conversations of yesterday's internet, to today, the actual science behind GLP-1s, and all the weird things doctors have been learning about them in their last three years of widespread deployment.

• 21:02PJ Vogt?

  Welcome back to the show. So can you tell me, literally, just like, what are GLP-1s doing inside of your body? Like, what are the mechanics of how these drugs work?

• 21:14Speaker 01

  Okay, so- When we're talking about GLP-1s as a class, we're talking about this class of medications. The first one actually came out in 2005. But like this popular conversation is referring to the ones that have come out in the last couple of years. And the sort of first one is semaglutide, which is Ozempic or Wegovy. Then the second one that's already approved and been on the market for a couple of years is terzepatide, which is Zepbound or Mounjaro. And then there's this one in the pipeline that I literally cannot pronounce, the one with the R.

• 21:48PJ Vogt?

  Redetrutide.

• 21:49Speaker 01

  Redetrutide is like the worst possible name.

• 21:51PJ Vogt?

  Yes.

• 21:52Speaker 01

  Like, I can't spell it, I can't say it. So semaglutide is this peptide that is a GLP-1 agonist. An agonist means that it's a peptide that binds to the GLP-1 receptor in the body. And GLP-1 in the body does a couple of different things. It slows gastric emptying, so it makes your stomach stay full longer.

• 22:14PJ Vogt?

  Like, not the feeling, not just the feeling of being full, but literally like, if I eat a salad, it stays there.

• 22:19Speaker 01

  Exactly. That does absolutely increase your fullness and gets you to fullness faster.

• 22:23PJ Vogt?

  Yeah.

• 22:24Speaker 01

  It also does increase your sense of fullness by working on like hormone receptors in the brain, and it decreases hunger and increases satiety. And then it, and this is why it's really important and works in diabetes, it works on glucose balance. And so it provokes the pancreas to release insulin in response to high glucose levels. So it doesn't cause your pancreas to just like willy-nilly release insulin all the time, but it augments the insulin response to high glucose levels in your body.

• 22:56PJ Vogt?

  And what's the relationship between, like, glucose enters my body when I eat like sugar or bread or something like that. What's the relationship between glucose and insulin?

• 23:03Speaker 01

  So when you eat anything that has carbohydrates in it, it gets broken down to release glucose, which is like sugar, in your blood. In response to glucose in the blood, the pancreas, which is like an organ in the back of your belly, releases insulin, which is a hormone. Insulin helps your muscles take the glucose out of your blood into the muscle and use it for energy. What happens in people with type 2 diabetes or people with prediabetes is they develop insulin resistance, which means that they have decreased response to insulin, which means they are less effective at taking the glucose out of your blood. And that means that your body needs to release more insulin in order to take that glucose out of your blood.

• 23:45PJ Vogt?

  Yeah.

• 23:46Speaker 01

  So for diabetics, who often have very high levels of glucose, just like circulating in the blood, high levels of glucose is called hyperglycemia. It has all sorts of downstream effects. It hurts your eyes, it hurts your kidneys. Eventually, it contributes to plaque buildup in your arteries, which can cause heart attacks and strokes. So what you want to do in diabetics is get their glucose levels, their average circulating glucose levels down. And GLP-1 agonists help do that by signaling to your pancreas when you have a glucose spike to release insulin, so that the glucose spike doesn't spike too high, basically. It helps sort of maintain your glucose levels within a range that your body can handle.

• 24:28Speaker 01

  And GLP-1 agonists, through that sort of combination of effects, the semaglutide, like would go via ZMPX, lead to like 10 to 15% body weight loss over the course of a year in the studies. But the thing that I think is really interesting about these drugs, and one of the reasons that they've inspired so much excitement is because they've had effects that we sort of anticipated, that were like targeted effects in the initial trials, improved blood sugar control and weight loss. And then they've had a bunch of unexpected downstream effects, probably related to weight loss and better blood sugar control, like they prevent heart attacks, they prevent strokes, they prevent people from progressing to diabetic kidney disease, they seem to

• 25:13Speaker 01

  improve people's knee arthritis, which like was really unexpected, they seem to improve heart failure. And then they also have this potential effect around addiction. And that's interesting because you really can't attribute that impact to weight loss. So like-

• 25:33PJ Vogt?

  There's no reason to think that if I'm 225 pounds or 180 pounds, I should want to drink more or less.

• 25:40Speaker 01

  Right, exactly. Other than maybe there's some psychological impact, et cetera, et cetera. But what we're sort of interested in is- It's revealed that there are GLP-1 receptors in places where I think we didn't totally recognize they were there, didn't fully recognize their potential role in things that we weren't thinking about. So there are GLP-1 receptors in like the dopamine reward circuitry in your brain. And one sort of hypothesis around the addiction stuff, or the strongest hypothesis, is that GLP-1 agonist binding there is interrupting reward circuitry pathway stuff in a way that for people who have strong reward pathways built around addictive behaviors, like it interrupts that.

• 26:24PJ Vogt?

  And is it like these sort of unexpected positive effects, the ones that are sort of surplus effects that go beyond what you would have modeled as likely benefits of just like losing weight? Does it suggest that maybe being like a certain amount of overweight can be more dangerous to our health than we understood? Or is it more like these things are just doing things in places that we don't understand?

• 26:52Speaker 01

  I think it's the first. I think that one of the things that's really interesting about the diverse array of effects that the GLP-1 drug seemed to have is that it suggests another fact that obesity, in which people who study obesity have long asserted, is a pathological condition that has consequences way beyond just being overweight and moving around the world in a bigger body. Having a lot of excess fat tissue on your body changes all sorts of hormone signaling and homeostasis mechanisms in your body. So losing that adipose tissue, that fat tissue, makes a huge difference in changing how your body self-regulates. And that seems to improve a whole bunch of things that we maybe didn't

• 27:37Speaker 01

  totally anticipate. There's this sort of hand wavy thing that the GLP-1s decrease inflammation, which is true, we sort of do know that, that they decrease inflammatory markers in the body. And just seeing all the different ways in which decreasing inflammation seems to help people is really fascinating.

• 27:54PJ Vogt?

  Yeah.

• 27:56PJ Vogt?

  You've described the known benefits. You described that there's some like sort of, I don't want to say unknown possible benefits, but like question marky things that look good.

• 28:04Speaker 01

  A million things that are like question marky things that look good. Like I should just list some of them because it's so exciting. Cancer prevention. So we know this is another one where like, on the one hand, we know that there are a bunch of cancers for which obesity is a risk factor. Breast cancer is like that. Colon cancer is like that. GLP-1 seemed to help with those. There are a bunch of cancers where we don't think of obesity as being a risk factor, where GLP-1's because of this anti-inflammatory sort of impact, we're not totally sure, may also play a role. So there are trials to look at cancer prevention. There are trials to look at Alzheimer's prevention. The first Alzheimer's prevention trial was negative, which means like the drug didn't make a difference, but I don't think it's

• 28:49Speaker 01

  conclusively negative that it doesn't help with Alzheimer's prevention or treatment necessarily. There's more trials to be done there. There are trials happening in Parkinson's disease. Like, these are big, extremely common conditions that either lead to death or that totally derail people's lives. And so the potential benefits that are still under-characterized or unproven are super exciting.

• 29:12PJ Vogt?

  And what are the current unknown or questionable possible harms that you're tracking?

• 29:18Speaker 01

  I mean, one that's sort of been studied some, but I think not in a way that's super, super conclusive, is for some people it does seem to provoke a depression. There's been this concern about increased suicidality that has not borne out in studies thus far, but like is on the radar as a thing that people are concerned about. But these psychiatric neurologic complications I'm interested in and paying attention to. The most common side effects with these drugs are the GI side effects. So like, bad nausea, and vomiting, and constipation. And so- I'm really interested in both increased clarity around what standard of care looks

• 29:59Speaker 01

  like for prescribing them to minimize those side effects and whether these future like GLP-1, 2.0, 3.0, 4.0s are going to improve that side effect profile because that would actually make a very big difference.

• 30:12PJ Vogt?

  Right, because there's people that can't tolerate the side effects.

• 30:14Speaker 01

  Yeah, I mean, some people are really nauseous and vomit at the beginning because they just haven't figured out how to eat on the drugs, like they're still eating too much. But some people have like constipation that they just can't tolerate. Some people are persistently nauseous in a way that doesn't get better. For most people, it gets better. But that's a real like rate limiting step.

• 30:33PJ Vogt?

  So there's a world of discourse and media, which I belong to, which bungled this story for at least a year. In the world of the patient populations who you treat, like, what was actually happening far away from discourse? Can you just tell me stories like from early on, like what type of patient was taking these medicines at your clinic? And how is it affecting them?

• 30:57Speaker 01

  Sure. So I work in New York City. New York State has generous Medicaid. New York City's public hospital system has its own pharmacies and they did some amazing job, I don't totally understand, in which they were able to provide access to the GLP-1s even during the period when it was very, very hard to get them at sort of regular community pharmacies. And so between both that sort of generous insurance and that access in our hospital pharmacy, I have had this incredible good fortune of being able to prescribe Ozempic for diabetic patients since like 2023 or 2024, who are poor and

• 31:41Speaker 01

  otherwise would not have access to it, right? And this is like a huge issue is that like for most patients like my patient population, they aren't on it yet because their insurance doesn't cover it.

• 31:52PJ Vogt?

  Yeah.

• 31:52Speaker 01

  Or if their insurance covers it, it covers it only for a very narrow set of indications and they have trouble getting it or whatever it is. My patients have been able to get it the whole time. And I do think it's sort of like a

• 32:05Speaker 01

  Miracle breakthrough in primary care for underserved populations that have the morbidity burden that my patients have. So, most of my patients have diabetes and high blood pressure and high cholesterol and some degree of kidney disease and maybe some degree of other complications of diabetes, like retinal disease in their eyes and fatty liver disease. Most of my patients also have some addiction history in my homeless clinic, so alcohol or other substances. And it's been my experience that for the patients for whom I've been able to prescribe Ozempic, which is the one that I've been able to get paid for, it really does help with all of those things. Like, their diabetes improves,

• 32:48Speaker 01

  they lose weight, their chronic pain improves, their blood pressure improves, their cholesterol markers improve, and patients really like it. I mean-

• 32:58PJ Vogt?

  What do they say?

• 32:58Speaker 01

  Like, I had this great paranoid schizophrenic lady who was on it. She was the first patient I ever prescribed it to in primary care. And she was in my office, and she's sort of like, a little bit psychotic at baseline, but she takes her medicines. So, she's telling me some story, like, I kind of can't follow about like, some people who have been like, tapping her phone. And then I said, "Oh, wow, you lost like, 12 pounds," or something, because I'm looking at her chart. And she pauses and she like, locks in, and she goes, "I haven't weighed this much since 1996."

• 33:36Speaker 01

  And I died. Like, I was like, "You go, girl. Like, amazing. So happy for you." And that's like, that's been true for a bunch of my patients, that they feel better in their bodies, both psychologically and physically. And they don't work for everybody. There are certainly, you know, 5 to 10% of people who don't tolerate them because the side effects are too much. Like, some people just get much more nauseous than the average person, and then they're just like, "I can't do this. I don't like it." A few people have said, more in my personal life than in my practice, that they thought that they felt low on them, that it made them feel a little bit depressed. I haven't had that happen in my practice, but, you know, that's just to say that there are a bunch of reasons why some people don't tolerate them. But for people who tolerate them, and for whom they work, they're an incredible intervention. Most of my patients

• 34:20Speaker 01

  are on like, 8 to 10 medicines a day. And for them to be able to take one shot a week, lose weight, improve their diabetes, improve their high blood pressure, improve their high cholesterol, you know, carrying less weight and also have less inflammation in their body. So their pain is better, their depression is better. Like, that's an extraordinary thing to be able to offer them. It's not everybody's experience, but for people for whom it works, like, it works better than any other single intervention I've ever given someone other than curative ones. And so, like, I'm unbelievably grateful for them and I'm incredibly excited about them. You know, like, I think as there's this arms race in developing better, more effective, more targeted GLP-1s, and as we get more

• 35:05Speaker 01

  and more studies about how to dose them correctly for different conditions, et cetera, et cetera, like, you know, I mean, it already has, but it will absolutely revolutionize primary care practice.

• 35:20PJ Vogt?

  Dr. Bedard says that part of this revolution has come because, maybe surprisingly, maybe not, one side effect of the huge demand surge for these drugs in 2023 and 2024 is that the price has been driven down. When the manufacturers of drugs like Ozempic couldn't meet demand, compounding pharmacies entered the marketplace, selling compounded versions at a much lower price. That ended up pushing prices further down, even on the name brand GLP-1s. So now, semaglutide, which not so long ago cost $1,200 a month without insurance, can be found online for as low as $150 a month. A healthcare market that, for once, seems to have kind of sort of worked eventually. We're going to take one more break, and when

• 36:01PJ Vogt?

  we come back, Dr. Bedard gives us her take on people who are taking these drugs for decidedly off-label use.

• 36:23PJ Vogt?

  Welcome back to the show. Do you, just in your social life, do you have like non-patient people, like friends, family members still asking about the drugs?

• 36:32Speaker 01

  Oh, constantly.

• 36:33PJ Vogt?

  Constantly.

• 36:34Speaker 01

  Constantly. Like, I take it like unofficial as I'm like, consulted day.

• 36:38PJ Vogt?

  What do you tell people right now?

• 36:40Speaker 01

  I'm, I mean, I am very GLP-1 supportive. So, you know, it's case to case. Like, it's not for everybody. But I will give you sort of examples of like, the kinds of things. Like, you know, I have lots of women in my life who are struggling with postpartum weight gain, or like, pregnancy weight gain and not being postpartum, feeling overweight. Or people who, one of their real anxieties about getting pregnant again is that they gained a huge amount of weight and they don't feel like they're back in their own bodies and they don't want to gain more. I'm really supportive of people using a GLP-1 for a period of time to help them lose, you know, weight that they gained really suddenly and are having a hard time losing. There are obviously some people who have long histories

• 37:23Speaker 01

  of eating disorders in their lives, right? And where you think, I think if you do this, this is not going to be great for you, actually. Like, I think that this is reigniting a series of obsessions that like, you've done a lot of work to try to get past. For those folks, I don't think that they should, you know, entertain the idea of a GLP-1. But for lots of people, I think it's a fine thing to do.

• 37:41PJ Vogt?

  Do you talk to people who are talking about using it, I guess off-label, to manage addictions?

• 37:47Speaker 01

  I have, so, I don't, I know one guy who was taking it so that he would post on Twitter less.

• 37:56PJ Vogt?

  Really?

• 37:57Speaker 01

  Yeah.

• 37:58PJ Vogt?

  Did it work?

• 37:59Speaker 01

  He said so. And then he's posting a lot recently, so maybe he's off. I don't know.

• 38:02PJ Vogt?

  If I really thought it was a cure for Twitter use, there's people, I would, no, I would stand outside other people's houses with like, a blowgun.

• 38:12Speaker 01

  I mean, you know, I think, yes, I'd absolutely have people who, I have a close friend who's primary motivation in trying it was that he wanted to drink less. He also probably wanted to lose 10 or 15 pounds, but like, probably wouldn't have taken it just for that alone.

• 38:27PJ Vogt?

  Yeah.

• 38:27Speaker 01

  Asked and I said, yeah, try it. See how you tolerate. You know, the other thing is that they just are quite safe. That doesn't mean that they're safe for everybody to take for 60 years, week after week. You know, like, we don't totally have exactly that data, but we have 20 years of data about this class of medicines and we have a pretty good sense of there is a very narrow slice of the population who they're totally inappropriate for. If you've had a family history of certain rare cancers, for the majority of people, giving them a shot and seeing how you tolerate is totally appropriate and fine. And so this friend like took them, he didn't identify as an alcoholic, but he identified someone who wanted to drink less and who drank daily.

• 39:05Speaker 01

  And for this friend, he took them for six months or something, or four months, totally changed his relationship to drinking. I think he's been off now for a little while and he said he's not back to drinking the way that he was. He feels that relationship feels altered for him, even if he's not as suppressed in his desires, he maybe was when he was like on the medicine, week after week.

• 39:32PJ Vogt?

  I had one last question for Dr. Bedard. I wanted to know if she had a perspective on a class of drugs that are adjacent to, but in my view, fairly different from GLP-1s? Internet peptides, the wilder west of molecules many people are now using, drugs we've covered elsewhere on the show.

• 39:49Speaker 01

  I think that I think that it is both GLP-1s and peptides, to some degree, are part of a larger shift in health wellness medicine, which is this like paradigm shift between thinking of medicines as things that we use to treat illness, to thinking of pharmaceutical products as something that we offer people to help them feel the way they want to feel.

• 40:19PJ Vogt?

  Is that a bad shift? Is that a neutral shift?

• 40:21Speaker 01

  It's a complicated shift, I think. So, you know, the, the better example to me than peptides is like the use of hormone supplementation for a million different indications, right? Like, that's another huge discourse. It's like, you know, Women taking estrogen supplementation in their early 40s when they start to feel what they self diagnose as perimenopausal symptoms, women on testosterone, there's been a bunch of essays about that, men on test, you know, like, it's a very different way of conceptualizing the role of healthcare than it's not why I went into healthcare. And it's also different from the sort of paradigm I trained in. But I'm also a little bit trying to remain neutral about this and thinking about the changing relationship

• 41:06Speaker 01

  between patients and providers to one that's a more sort of shared goal setting, shared decision making model, which doesn't quite answer your peptides question, but I kind of see all of like the peptides, the GLP ones, the cosmetic procedure stuff. It's like all part of a thing of like, I, I don't feel the way I want to feel in my body. I don't look the way that I want to look in my body, et cetera, et cetera. I'm, I'm going to seek medical intervention to help me become the thing that I want to become. I, I have really complicated reactions to it, but I'm, I don't yet have a definitive opinion about it. I'm really trying to think it through.

• 41:40PJ Vogt?

  I can't tell if what you're describing is that interventions that we just would have understood as cosmetic before are becoming much more socially acceptable, or if it's more complicated, which is that like interventions like we thought of as cosmetic, we're now in our own minds labeling as medical.

• 41:56Speaker 01

  I think it's the second one. So I think that we have, in a weird way, medicalized a lot of the experience of being like in the human life cycle, you know?

• 42:07PJ Vogt?

  Yeah.

• 42:07Speaker 01

  And that's complicated, you know? And again, like, these are all sort of questions and discourse topics, et cetera. So they're so far afield from my medical practice and my patients' lives and my patients' bodies. And they're so far afield from sort of what are the things that sick people actually live with? What are the things that actually kill people, et cetera, et cetera? So with this sort of large caveat that all of my initial anxieties about the GLP one discourse apply to this other sort of wider discourse around other interventions that are for self fulfillment, but are sort of being medicalized. I'm trying to be like a little bit thoughtful before I just sort of react to them as a knee jerk moral panic around those.

• 42:48PJ Vogt?

  But it's like you feel uneasy, but you feel uncertain about your uneasiness.

• 42:51Speaker 01

  Yeah, I'm like really working through it.

• 42:54PJ Vogt?

  I think that's a, an actually honest position.

• 42:56Speaker 01

  Thank you.

• 42:59PJ Vogt?

  Thank you for talking about this.

• 43:00Speaker 01

  My pleasure. Thank you for having me.

• 43:08PJ Vogt?

  Dr. Rachel Bedard, she's a doctor and writer. We'll have a link to her story about the rise of Ozempic in the show notes. Also, I have to say, there was one more part of this conversation, which it was a part I found myself talking the most about with friends the week afterwards, but it was on a slightly adjacent topic. So we got more into this idea of cos-medicine, like the place where cosmetic interventions and medical interventions kind of meld together, and about how there are middle-aged people who are thinking about interventions like taking testosterone or estrogen, or going to the dermatologist for lasers to try to look more the way they think Anne Hathaway looks, or men going to Turkey to get a new hairline. I don't know how we're supposed to think about this era where looking older seems

• 43:52PJ Vogt?

  to be becoming more optional, where many people on the internet seem forever 35. And talking to Dr. Bedard, who is also working this stuff out, it really helped me. These ideas have already been swirling around my brain. It settled them a little bit. If you want to hear that conversation, we're going to publish it as an extra small feature on incognito mode. You can sign up for that at searchengine.show. If you're already signed up, it is in your feed now.

• 44:48PJ Vogt?

  Search Engine is a presentation of Odyssey. It was created by me, PJ Vogt, and Trudy Pinamaneni. Garrett Graham is our senior producer. Emily Multer is our associate producer. Theme, original composition and mixing by Armin Bazarian. Our production intern is Piper Dumont. Piper also fact-checked this episode. Our executive producer is Leah Reese-Dennis. Thanks to the rest of the team at Odyssey, Rob Morandi, Craig Cox, Eric Donnelly, Colin Gaynor, Moira Curran, Josefina Francis, Kirk Courtney, and Hillary Schuff. Also, if you have a business which you would like to advertise on our show, please email us. Email address is [email protected]. Subject line: Advertising. If you'd like to support our show, get ad-free episodes, zero reruns, and bonus audio, including

• 45:31PJ Vogt?

  this week, please consider signing up for Incognito Mode at searchengine.show. Thanks for listening. We'll see you next week.