Latest / Wellness, Actually with Emily Oster & Perry Wilson, MD / Rerun, Actually - What's the deal with GLP-1s?

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Rerun, Actually - What's the deal with GLP-1s? · Wellness, Actually with Emily Oster & Perry Wilson, MD

• 0:01
  Speaker 1: Perry.
• 0:02
  Speaker 2: Emily.
• 0:03
  Speaker 1: It's conference season.
• 0:04
  Speaker 2: It is. That means we're running another rerun, actually, episode
• 0:09
  Speaker 2: this week.
• 0:10
  Speaker 3: And this is another good one from our early days,
• 0:12
  Speaker 3: back when GLP-1s were everywhere and before GLP-1s were also everywhere.
• 0:18
  Speaker 3: You know, I saw someone today talk on the Instagram
• 0:21
  Speaker 3: about how GLP-1s are their travel hack. They just take
• 0:25
  Speaker 3: them when they're traveling so they don't have to eat
• 0:28
  Speaker 3: on the airplane.
• 0:30
  Speaker 2: Okay. That's an off-label use. But it's exciting. Back in
• 0:36
  Speaker 2: this episode, the pill form actually had just hit the market.
• 0:39
  Speaker 2: And now we have commercials for the pills starring Martha Stewart.
• 0:44
  Speaker 2: So that's where we are in the culture.
• 0:46
  Speaker 1: Martha Stewart, she looks great.
• 0:47
  Speaker 2: She's doing fine.
• 0:49
  Speaker 3: But what's still relevant about this episode is we actually
• 0:52
  Speaker 3: went really far back looking at the history, the development
• 0:55
  Speaker 3: of the medication, not just how it's being used or
• 0:58
  Speaker 3: abused today.
• 0:59
  Speaker 1: And I think people will learn something.
• 1:02
  Speaker 2: Totally. Enjoy the conference. And here's the episode.
• 1:06
  Speaker 1: Hey, Perry. How you doing?
• 1:09
  Speaker 2: I'm good. Emily, nice to see you.
• 1:11
  Speaker 3: Nice to see you. Okay, today we are talking about GLP-1s.
• 1:14
  Speaker 3: I'm going to ask you some questions. Do you know
• 1:16
  Speaker 3: anyone using a GLP-1?
• 1:18
  Speaker 2: Well, wait, I've never heard of this. What is a GLP-1? No,
• 1:22
  Speaker 2: I'm just kidding. Yes, of course I know people on GLP-1s.
• 1:26
  Speaker 1: Do you know people using them off-label?
• 1:28
  Speaker 2: Yes.
• 1:29
  Speaker 3: Do you know people who are using other people's GLP-1s
• 1:32
  Speaker 3: from their refrigerator?
• 1:33
  Speaker 2: Yes.
• 1:34
  Speaker 1: Do you know people who are microdosing GLP-1s? Yes. Yes.
• 1:38
  Speaker 3: Yes. Do you know any, wait, do you know anyone
• 1:41
  Speaker 3: who is microdosing GLP-1 so they can focus better at
• 1:44
  Speaker 3: their tech job?
• 1:47
  Speaker 2: Okay, you got me there. I will take a drink.
• 1:50
  Speaker 1: I'm a yes on that one.
• 1:52
  Speaker 2: Wow. I want to hear more, but it might have
• 1:54
  Speaker 2: to happen offline.
• 1:58
  Speaker 1: I'm Emily Oster. I'm an economist and a data expert.
• 2:01
  Speaker 2: And I'm Perry Wilson. I'm a medical doctor.
• 2:04
  Speaker 1: It's Thursday, March 5th, 2026. And this is Wellness Actually.
• 2:09
  Speaker 2: Because you're getting a staggering amount of health and wellness
• 2:12
  Speaker 2: information nowadays from every source imaginable. And some of it
• 2:16
  Speaker 2: is awesome.
• 2:17
  Speaker 1: And some of it is, well, actually bullshit.
• 2:21
  Speaker 3: Fortunately, we're both people who know how to read studies,
• 2:25
  Speaker 3: how to parse the data, and can tell you what's
• 2:27
  Speaker 3: worth thinking about and what you can safely ignore.
• 2:30
  Speaker 2: But before we dig in, a note that this podcast
• 2:32
  Speaker 2: is for educational purposes and should not be construed as
• 2:35
  Speaker 2: medical advice. We don't know your unique situation, so talk
• 2:38
  Speaker 2: to your doctor for personal health decisions.
• 2:41
  Speaker 3: This week, we're asking what's the deal with GLP-1s, and
• 2:45
  Speaker 3: you will get our highly official thumbs up or thumbs
• 2:48
  Speaker 3: down verdict after the break.
• 3:02
  Speaker 1: All right, Perry, GLP-1s. So I want to.
• 3:05
  Speaker 3: Set the stage here a little bit because I think
• 3:07
  Speaker 3: that there's a kind of GLP-1 1.0 conversation that people
• 3:11
  Speaker 3: can hear like, what are these?
• 3:13
  Speaker 1: Do they work for weight loss? And we will touch
• 3:15
  Speaker 1: on that.
• 3:15
  Speaker 3: But I think at this point, this is so ubiquitous
• 3:18
  Speaker 3: that people probably don't want to hear like GLP-1s are
• 3:21
  Speaker 3: effective for weight loss. I actually want to focus most
• 3:24
  Speaker 3: of our conversation, if you're up for it, on thinking
• 3:27
  Speaker 3: about the sort of 2.0 questions. So If people have
• 3:31
  Speaker 3: lost weight, what about weight regain? What are the other
• 3:33
  Speaker 3: things this might work for? What are the big concerns
• 3:36
  Speaker 3: people have? What about the long-term effects? There are some
• 3:40
  Speaker 3: interesting economic questions, which I'm dying to discuss.
• 3:43
  Speaker 2: I love it. This is not freshman year anymore. Welcome
• 3:45
  Speaker 2: to Senior Seminar. Exactly.
• 3:47
  Speaker 1: Senior Seminar, GLP-1s.
• 3:48
  Speaker 3: Okay, but before we get to, or maybe as part
• 3:51
  Speaker 3: of Senior Seminar... Can we talk about the Gila monster?
• 3:56
  Speaker 3: Is it Gila monster or Gila monster is my first question.
• 3:59
  Speaker 3: And can you tell me why it's such an important animal?
• 4:01
  Speaker 2: I say Gila monster. I don't know if that is correct.
• 4:06
  Speaker 2: You can write to us at wellnessactually.fm and correct everything
• 4:09
  Speaker 2: we say. It is important. This is so interesting. So
• 4:12
  Speaker 2: GLP-1 is a substance produced by your body and has
• 4:16
  Speaker 2: been known since the 70s. And even its effects were
• 4:20
  Speaker 2: known in the early 80s. So they took people and
• 4:24
  Speaker 2: they gave them infusions of human GLP-1. And what they
• 4:27
  Speaker 2: found is that their gastric emptying really slowed down. And
• 4:30
  Speaker 2: they reported more satiety. So they weren't as hungry. But
• 4:34
  Speaker 2: there was this problem. And that's that GLP-1 that your
• 4:37
  Speaker 2: body makes has a half-life of about a minute. And
• 4:40
  Speaker 2: so as long as it's directly infusing into your vein,
• 4:44
  Speaker 2: you don't feel hungry. But once you disconnect the IV,
• 4:47
  Speaker 2: you do. So not a viable product for weight loss, obviously.
• 4:51
  Speaker 2: And that was the state of things for 10 years
• 4:54
  Speaker 2: or so. And then we get to a weird lab
• 4:58
  Speaker 2: at the NIH. A guy named Jean-Pierre Routhman was working
• 5:03
  Speaker 2: in John Pisano's NIH lab. testing venoms of various venomous animals.
• 5:10
  Speaker 2: This is one of those examples of like basic science.
• 5:11
  Speaker 2: Like they had no idea what they were looking for.
• 5:13
  Speaker 2: It was just like, venom's interesting. We should know more
• 5:16
  Speaker 2: about venom and great. This guy, uh, Ralphman's job was
• 5:20
  Speaker 2: to extract venom from the Gila monster. And he noticed
• 5:24
  Speaker 2: that when he injected this venom into mice, it did
• 5:27
  Speaker 2: weird things with their blood sugar and their pancreas. He
• 5:29
  Speaker 2: wasn't sure what it was. In 1992, a scientist named
• 5:32
  Speaker 2: John Ang isolated the protein in Gila monster venom and
• 5:36
  Speaker 2: that was causing all these blood sugar issues. It was
• 5:39
  Speaker 2: called Exendin-4. And that was developed into a drug called
• 5:44
  Speaker 2: Exenatide or Bayeta, the first GLP-1 drug, which was FDA approved.
• 5:50
  Speaker 2: Do you want to guess when?
• 5:52
  Speaker 1: 2005.
• 5:53
  Speaker 2: This is not new science. But what was amazing about
• 5:56
  Speaker 2: the Gila monster venom is that protein in the venom
• 5:59
  Speaker 2: or that peptide in the venom looked like human GLP-1,
• 6:03
  Speaker 2: bound to the same receptor as human GLP-1, but it
• 6:06
  Speaker 2: didn't break down in the blood in a minute. It
• 6:08
  Speaker 2: broke down over the course of about a day. And
• 6:11
  Speaker 2: so you could get away with injecting it or the
• 6:14
  Speaker 2: cleaned up variants that was eventually produced called exenatide once
• 6:18
  Speaker 2: a day. And all of a sudden this was a
• 6:21
  Speaker 2: viable product.
• 6:22
  Speaker 1: So I just want to be clear, this is a peptide.
• 6:24
  Speaker 3: So for people who listened to the earlier episode on peptides,
• 6:27
  Speaker 3: this is an example of a peptide that is approved,
• 6:31
  Speaker 3: not like the Wolverine stack.
• 6:33
  Speaker 1: So go back to that episode for context there. Yeah.
• 6:36
  Speaker 3: So, OK, I think one interesting follow up question before
• 6:39
  Speaker 3: we get to some of these details is actually a
• 6:41
  Speaker 3: question of why now we're discussing this.
• 6:44
  Speaker 1: So if 20 years ago.
• 6:46
  Speaker 3: We developed this venom, why is it now that we
• 6:50
  Speaker 3: are seeing so much more of this, which feels like
• 6:54
  Speaker 3: it's kind of come up in the last three years?
• 6:56
  Speaker 3: So what is is there another science breakthrough that is
• 7:00
  Speaker 3: more recent?
• 7:00
  Speaker 2: Not really. It's been just kind of a– as these
• 7:03
  Speaker 2: things kind of go, like once the class is discovered,
• 7:06
  Speaker 2: it's like, okay, this class of chemicals is discovered. There's
• 7:09
  Speaker 2: iterative improvements over time and basically the improvements have been
• 7:13
  Speaker 2: two things. Number one, increased potency, which means– that they've
• 7:16
  Speaker 2: developed peptides that bind a little more tightly to the
• 7:18
  Speaker 2: GLP-1 receptor in our cells, and two, increased half-life. So
• 7:22
  Speaker 2: where semaglutide, which also some people say semaglutide, but I
• 7:26
  Speaker 2: say semaglutide, or ozempic came along with a once-weekly dose
• 7:30
  Speaker 2: because it was stable in your blood for a much
• 7:32
  Speaker 2: longer period of time, had a much longer half-life. That's
• 7:35
  Speaker 2: where you start to get people willing to think about
• 7:39
  Speaker 2: this for treatment of obesity. Most people without diabetes aren't
• 7:43
  Speaker 2: comfortable injecting themselves once a day with a product. And
• 7:46
  Speaker 2: in fact, even people with diabetes, no one loves injecting themselves, right?
• 7:50
  Speaker 2: And so... So once a week was a thing. There
• 7:53
  Speaker 2: was another milestone in the obesity literature, which was this
• 7:58
  Speaker 2: magical 10% weight loss threshold, which had always been the
• 8:03
  Speaker 2: arbitrary marker of, is this drug successful for weight loss?
• 8:06
  Speaker 2: And Bayeta, the first GLP-1, was not. It led to
• 8:10
  Speaker 2: some weight loss, about 2% to 3% over the course
• 8:12
  Speaker 2: of a year, but just wasn't potent enough. And it
• 8:14
  Speaker 2: was really, and still is used for diabetes control, blood
• 8:17
  Speaker 2: sugar control. You got the first greater than 10% weight
• 8:20
  Speaker 2: loss effect with loraglutide, which came out later. And that
• 8:23
  Speaker 2: sort of set off the arms race that we have now,
• 8:26
  Speaker 2: where you're just inventing drug after drug that are more
• 8:29
  Speaker 2: potent and more potent. And of course, like the most
• 8:31
  Speaker 2: recent trial, Lilly's new drug, which I can't even say.
• 8:36
  Speaker 1: Don't even try.
• 8:37
  Speaker 2: Retratrutide. had a 28% year-on-year weight loss, which is insane.
• 8:45
  Speaker 1: Okay.
• 8:45
  Speaker 3: So right now we find ourselves in a moment where
• 8:47
  Speaker 3: the two medications that people are most commonly using for
• 8:50
  Speaker 3: weight loss are Wagovi and Zepound. Wagovi is semaglutide. It's
• 8:56
  Speaker 3: the ozempic equivalent, but prescribed for weight loss. Zepound is trizepatide.
• 9:01
  Speaker 3: It's the manjaro equivalent, but prescribed for weight loss. Both
• 9:05
  Speaker 3: of these lead to something between 15% to 20% weight
• 9:11
  Speaker 3: loss in the first year. In the trial data, they
• 9:13
  Speaker 3: are both served through a weekly injection that people give themselves.
• 9:19
  Speaker 3: And the next thing that's coming is a set of,
• 9:22
  Speaker 3: we're going to keep seeing innovation here. The next thing
• 9:25
  Speaker 3: that's coming is an oral form from Eli Lilly, which has.
• 9:28
  Speaker 1: A slightly lower amount of weight loss.
• 9:30
  Speaker 3: But my guess is that the uptake will be very
• 9:32
  Speaker 3: high because people would rather take a pill than have
• 9:35
  Speaker 3: an injection. And So we really find ourselves in a moment,
• 9:38
  Speaker 3: this is kind of the Ozempic 1.0, where these medications
• 9:42
  Speaker 3: are incredibly effective for weight loss. They're much more effective
• 9:44
  Speaker 3: than pretty much anything we have had in terms of
• 9:47
  Speaker 3: diet and exercise.
• 9:49
  Speaker 1: They just work really well.
• 9:51
  Speaker 3: And more and more things that are developed are going
• 9:54
  Speaker 3: to make them work better.
• 9:56
  Speaker 1: To the point, I think, you know, you discussed the
• 9:58
  Speaker 1: latest trial with 30%. weight loss.
• 10:00
  Speaker 3: Like people are starting to have a conversation about like,
• 10:02
  Speaker 3: what's too much? Like how much weight loss is too
• 10:05
  Speaker 3: much weight loss? Like 30% is a lot in a year.
• 10:07
  Speaker 3: And so we're kind of at the point where probably
• 10:11
  Speaker 3: it's almost enough, although people always like more. But I
• 10:15
  Speaker 3: think it's very clear that these are effective for weight loss.
• 10:17
  Speaker 3: And that is like the science is done on that
• 10:19
  Speaker 3: particular piece. A next interesting question is what about the
• 10:23
  Speaker 3: other benefits? So before we get into like the things
• 10:27
  Speaker 3: we're concerned about, these were originally prescribed for diabetes. They
• 10:30
  Speaker 3: are effective for weight loss, but we're starting to see
• 10:33
  Speaker 3: all kinds of claims like this is good for kidney disease.
• 10:37
  Speaker 3: It's good for cardiovascular disease. This is good for, you know,
• 10:40
  Speaker 3: I don't know, like cancer, cancer for everything. I mean,
• 10:43
  Speaker 3: which of these things are best supported? I'm going to
• 10:46
  Speaker 3: ask you because I think the one of the best
• 10:48
  Speaker 3: supported one is the kidneys and you are in fact
• 10:50
  Speaker 3: a kidney doctor.
• 10:51
  Speaker 2: Yeah, all these kind of off-target effects. And I think
• 10:54
  Speaker 2: it's good to think about the non-weight, non-diabetes effects based
• 10:59
  Speaker 2: on whether they are related to a reduction in weight
• 11:02
  Speaker 2: or are they something else entirely. So let's take cancer
• 11:05
  Speaker 2: as an example. So there have been several studies that
• 11:09
  Speaker 2: have shown– that the use of these drugs reduces the
• 11:12
  Speaker 2: rate of obesity-related cancers. So the classic obesity-related cancers, cancers
• 11:17
  Speaker 2: that are driven by some of the hormones that come
• 11:19
  Speaker 2: from fat and stuff like that, like breast cancer, cancers
• 11:22
  Speaker 2: of the GI tract, colon cancer, and the rates of
• 11:25
  Speaker 2: those things do go down. But it's plausible, we always
• 11:29
  Speaker 2: talk about biological plausibility, that the reason they're going down
• 11:31
  Speaker 2: is not because these drugs magically kill tumor cells, it's
• 11:34
  Speaker 2: because people lose weight, and weight is a risk factor
• 11:38
  Speaker 2: for the development of these types of cancers. That's a
• 11:40
  Speaker 2: similar mechanism for like a reduction in blood pressure, for example.
• 11:43
  Speaker 2: If you lose weight in any way, your blood pressure
• 11:46
  Speaker 2: goes down. Same thing for kidney disease, broadly speaking. The
• 11:50
  Speaker 2: more weight you have, the more metabolically active tissue you
• 11:52
  Speaker 2: have in your body, the more work the kidney has
• 11:54
  Speaker 2: to do. And in general, if you can give the
• 11:56
  Speaker 2: kidney less work to do, it's happy to not have
• 11:58
  Speaker 2: to do as much and they can kind of last longer.
• 12:00
  Speaker 2: I think it's probably similar for cardiovascular disease as well.
• 12:04
  Speaker 3: So I will say that I think that in some
• 12:06
  Speaker 3: of these trials, when they're looking at other kinds of
• 12:09
  Speaker 3: cardiovascular disease and so on, there's sort of some discussion
• 12:13
  Speaker 3: that maybe the effects are larger than you would expect
• 12:17
  Speaker 3: based on weight loss alone. So they're sort of trying
• 12:19
  Speaker 3: to do a kind of calibration. And then say, well,
• 12:22
  Speaker 3: maybe it's like a lot of the weight loss, but
• 12:25
  Speaker 3: then there's something that you get more. Although I think
• 12:28
  Speaker 3: that's obviously a very hard thing to sort of separate
• 12:30
  Speaker 3: fully in the data.
• 12:31
  Speaker 2: Yeah. And it relies on some assumptions of like, you know,
• 12:34
  Speaker 2: how many pounds of weight is equivalent to how many
• 12:37
  Speaker 2: millimeters of mercury of blood pressure that are always like
• 12:39
  Speaker 2: a little bit hand wavy. So that's all true. The
• 12:42
  Speaker 2: epidemic of obesity in our country and around the world
• 12:45
  Speaker 2: is driving much of the chronic disease epidemic. It just is.
• 12:50
  Speaker 2: And so anything that impacts obesity, whatever it is, is
• 12:52
  Speaker 2: going to reduce the rates of those diseases. That's cool.
• 12:56
  Speaker 2: But what always kind of gets me interested, and I
• 12:59
  Speaker 2: want to ask you this, Emily, are the things that
• 13:01
  Speaker 2: really can't plausibly be related to weight loss. So what
• 13:06
  Speaker 2: do you think about the fact that people report less
• 13:10
  Speaker 2: smoking or alcohol intake or gambling like this stuff.
• 13:13
  Speaker 3: Yeah. I mean, I think, so my sense is of
• 13:16
  Speaker 3: those things, the one that is most strongly supported in
• 13:18
  Speaker 3: the data is alcohol, partly because that's where we've studied
• 13:22
  Speaker 3: the most and partly because that's an activity that most
• 13:24
  Speaker 3: people engage in. There's a lot of reports in both
• 13:27
  Speaker 3: the data and just out in the world that people's
• 13:29
  Speaker 3: interest in alcohol declines as a result of this and
• 13:33
  Speaker 3: that other, you know, their interest in smoking, they're interested
• 13:36
  Speaker 3: in all these other kind of maybe what we consider
• 13:38
  Speaker 3: vices goes down One interpretation of the way these medications
• 13:43
  Speaker 3: work is that there's something about sort of almost like
• 13:47
  Speaker 3: sort of self-control, like inhibition value. And I mean, this
• 13:52
  Speaker 3: is consistent with when you talk to people who take
• 13:54
  Speaker 3: these medications. And I have not, but I've talked to
• 13:56
  Speaker 3: a lot of people. One of the things that is
• 13:58
  Speaker 3: very common for people to say is like it turned
• 14:00
  Speaker 3: off the noise.
• 14:01
  Speaker 1: Like my head was.
• 14:02
  Speaker 3: Full of food noise and I was always thinking about
• 14:05
  Speaker 3: food and I was always thinking about that.
• 14:07
  Speaker 1: And this made me think about it less.
• 14:09
  Speaker 3: And if you think about the way that a lot
• 14:11
  Speaker 3: of people feel about alcohol or smoking or whatever, it
• 14:13
  Speaker 3: is also that noise. It's like, I feel the noise.
• 14:15
  Speaker 3: I want to have a drink or I feel the noise.
• 14:16
  Speaker 3: I want to have a cigarette. You can imagine that
• 14:19
  Speaker 3: whatever is that mechanism, it.
• 14:21
  Speaker 1: Might work there.
• 14:22
  Speaker 3: Similarly, I know people who take this for focus, who
• 14:25
  Speaker 3: microdose like a ZEP bound for focus.
• 14:28
  Speaker 2: Yeah, talk to me about that. I've never heard that before.
• 14:30
  Speaker 1: I don't know. These guys in Silicon Valley do a
• 14:32
  Speaker 1: lot of weird stuff, Perry. And one of the things
• 14:36
  Speaker 1: is like, it really helps you focus.
• 14:37
  Speaker 3: It helps you not be distracted by whatever, food noise,
• 14:40
  Speaker 3: alcohol noise, smoking noise, other kinds of noise. Certainly, I
• 14:44
  Speaker 3: would not say that we have science or data or
• 14:46
  Speaker 3: evidence that supports that piece. But putting all of these
• 14:50
  Speaker 3: things together, it does feel like maybe there's something In there,
• 14:56
  Speaker 3: there's something about the way this is interacting with people's
• 14:58
  Speaker 3: brain chemistry that could be consistent with some of these effects. Actually,
• 15:03
  Speaker 3: there's someone, I believe there are some people thinking about
• 15:06
  Speaker 3: experimenting on providing people GLP-1s when they leave prison. And
• 15:11
  Speaker 3: one of the outcomes they would look at is recidivism.
• 15:13
  Speaker 3: And one interpretation of that is that basically if you
• 15:16
  Speaker 3: could turn down people's impulses to engage in alcohol.
• 15:20
  Speaker 1: And drugs and so on, they might actually be less
• 15:22
  Speaker 1: likely to return to prison.
• 15:24
  Speaker 2: Wow. Dude, fascinating. Totally fascinating.
• 15:27
  Speaker 1: That's interesting. Again, this is like we're on the- Yeah,
• 15:29
  Speaker 1: of course.
• 15:30
  Speaker 2: We're way out there.
• 15:30
  Speaker 1: We're way out there.
• 15:31
  Speaker 2: We're way out there. It really does seem like that
• 15:44
  Speaker 2: is not everything here. I did a quick review of
• 15:48
  Speaker 2: like where GLP-1 receptor is found in your body. So,
• 15:52
  Speaker 2: you know, what kind of cells express these receptors in
• 15:54
  Speaker 2: high levels? And yes, they are throughout the GI tract
• 15:57
  Speaker 2: and pancreas and things like that. But right up there
• 16:00
  Speaker 2: in terms of organ systems is the brain. So your
• 16:02
  Speaker 2: brain has these receptors. We do know that these peptides
• 16:05
  Speaker 2: can cross the blood-brain barrier. And once a drug can
• 16:08
  Speaker 2: cross the blood-brain barrier, and once you know there's receptors
• 16:10
  Speaker 2: on your neurons for that drug, it kind of opens
• 16:14
  Speaker 2: the door of anything being possible to some extent, right?
• 16:17
  Speaker 2: So all of these things are definitely plausible.
• 16:20
  Speaker 3: So if one thing people wonder about sometimes is when
• 16:22
  Speaker 3: you're on these and you lose weight, is it, quote,
• 16:25
  Speaker 3: the same as losing weight in other ways?
• 16:28
  Speaker 1: You know, is it.
• 16:29
  Speaker 3: Literally just this makes you eat less and you eat
• 16:31
  Speaker 3: less and then you lose weight, like can measure it
• 16:33
  Speaker 3: with the way you would lose weight, you know, if
• 16:35
  Speaker 3: you just literally ate less?
• 16:37
  Speaker 1: Is there something more than that or is that kind
• 16:39
  Speaker 1: of the whole business?
• 16:40
  Speaker 2: Oh, this is such a good question. Because so much
• 16:42
  Speaker 2: of what I see online, there is like an anti-GLP-1
• 16:48
  Speaker 2: current that is under there. And typically, the arguments do
• 16:52
  Speaker 2: go something like this. Like, this is not natural. This
• 16:55
  Speaker 2: isn't the real way to lose weight. And because it's
• 16:58
  Speaker 2: not the real way to lose weight, it does these
• 17:00
  Speaker 2: certain bad things. And I think the one that you
• 17:04
  Speaker 2: hear about the most is probably muscle loss. And people
• 17:07
  Speaker 2: come and are like, oh, no, you're not just losing fat.
• 17:10
  Speaker 2: You're losing muscle. And Emily, I know you've looked into this.
• 17:13
  Speaker 2: So I will ask you, is it true that if
• 17:16
  Speaker 2: I lose weight through other means like diet and exercise
• 17:19
  Speaker 2: that I only lose fat and don't lose muscle?
• 17:21
  Speaker 1: That is not true, Perry.
• 17:23
  Speaker 3: When you lose weight in any way, you lose both
• 17:26
  Speaker 3: fat and muscle. And some of that is like sort
• 17:29
  Speaker 3: of intimately linked because one of the things your muscles do,
• 17:33
  Speaker 3: actually the main thing for most of us our muscles
• 17:35
  Speaker 3: are doing, are moving us.
• 17:37
  Speaker 1: Around in the world.
• 17:38
  Speaker 2: Yes.
• 17:38
  Speaker 3: And so if you are heavier, your muscles are moving
• 17:41
  Speaker 3: more stuff. It's like you're constantly wearing a weighted vest.
• 17:44
  Speaker 3: And when you lose weight, even if you just lost fat,
• 17:47
  Speaker 3: your muscles will be like, great, we don't have to
• 17:49
  Speaker 3: have so much of us anymore because.
• 17:51
  Speaker 1: we aren't moving around so much weight.
• 17:54
  Speaker 3: And so there is like an inherent feature of losing
• 17:57
  Speaker 3: weight where you are going to lose some fat and
• 17:59
  Speaker 3: some muscle. And if you have a lot of fat,
• 18:01
  Speaker 3: you will lose relatively more fat, but no matter how
• 18:03
  Speaker 3: you lose weight, you are losing some muscle.
• 18:05
  Speaker 1: And that is also true on Ozempic.
• 18:07
  Speaker 3: And actually the study suggests it's no more true on
• 18:10
  Speaker 3: GLP-1s than it is with other kinds of diet. Like
• 18:12
  Speaker 3: you just, you lose some fat and some muscle.
• 18:14
  Speaker 2: Yeah, and typically about 30% to up to 50% of
• 18:18
  Speaker 2: weight loss can come from muscle regardless of what the
• 18:21
  Speaker 2: weight loss is. There is a little wrinkle here that
• 18:24
  Speaker 2: I don't see brought up often, but I'll say it
• 18:27
  Speaker 2: because we're in senior seminar. And that is that the
• 18:30
  Speaker 2: way that muscle mass gets assessed typically in these studies
• 18:34
  Speaker 2: is through a DEXA scan, which is sort of a–
• 18:37
  Speaker 2: think of it like an X-ray, but you can see
• 18:39
  Speaker 2: muscle tissue.
• 18:40
  Speaker 1: You do a whole episode. Influencers love a DEXA scan.
• 18:43
  Speaker 2: Oh, interesting. Okay. So DEXA scans don't actually distinguish between
• 18:48
  Speaker 2: muscle and what's called lean mass, just like non-fat, non-bone mass.
• 18:53
  Speaker 2: So they sort of assume that everything that isn't bone
• 18:56
  Speaker 2: and isn't fat is muscle, which is obviously not true.
• 19:00
  Speaker 2: You have organs and stuff like that. But it's more
• 19:02
  Speaker 2: than that, which is that fat infiltrates muscle. And DEXA
• 19:06
  Speaker 2: scans cannot determine how much of your muscle is infiltrated
• 19:10
  Speaker 2: by fat. It just looks like more muscle. You can
• 19:13
  Speaker 2: think of this as like the marbling of a steak, right?
• 19:16
  Speaker 2: Like if you fatten these cows, you get nice prime
• 19:19
  Speaker 2: rib and things like that. And it's really tastes delicious,
• 19:22
  Speaker 2: but it's actually bad for your muscle quality. And so
• 19:24
  Speaker 2: we don't, it may be that some of the fat
• 19:26
  Speaker 2: loss is happening within muscle, which is almost certainly a
• 19:30
  Speaker 2: good thing. But yes, you're going to lose muscle if
• 19:33
  Speaker 2: you lose weight, no matter how you lose weight. So Emily,
• 19:35
  Speaker 2: let's say I don't want to lose muscle, or at
• 19:37
  Speaker 2: least I don't want to lose as much muscle as possible.
• 19:39
  Speaker 2: Can I prevent this or am I doomed? Yeah.
• 19:42
  Speaker 3: So one of the totally fascinating like knock on impacts
• 19:48
  Speaker 3: of the Ozempic craze is the strength training craze. So
• 19:53
  Speaker 3: the idea that you sort of like, all of a
• 19:55
  Speaker 3: sudden you're on the GLP-1 for weight loss, but now
• 19:58
  Speaker 3: you need to do strength training.
• 19:59
  Speaker 1: And that's actually not crazy.
• 20:00
  Speaker 3: You know, we think about like, how do you retain
• 20:03
  Speaker 3: and build muscle? You retain and build muscle by exercising
• 20:06
  Speaker 3: and in particular by exercising in a way that you know, cardio, yes,
• 20:09
  Speaker 3: but also like by lifting stuff.
• 20:12
  Speaker 1: And so there's a kind.
• 20:13
  Speaker 3: Of combo here where you take the GLP-1 for weight
• 20:18
  Speaker 3: loss and you exercise for muscle retention, which tends to
• 20:22
  Speaker 3: be a good combo. And interestingly, many people report their
• 20:25
  Speaker 3: willingness to exercise and like get up and go to
• 20:27
  Speaker 3: the gym is greater when they're on a GLP-1, getting
• 20:29
  Speaker 3: back to potentially some of the stuff that we talked
• 20:31
  Speaker 3: about before around sort of impulse control.
• 20:35
  Speaker 1: The other thing is prioritizing protein, right?
• 20:37
  Speaker 3: So like so much of what's happening when people are
• 20:39
  Speaker 3: in GLP-1s is they eat less food, like fewer calories,
• 20:42
  Speaker 3: but making sure that those fewer calories are actually like
• 20:45
  Speaker 3: you're maintaining protein. The amount of protein shouldn't change that much,
• 20:51
  Speaker 3: whereas the amount of other things should change more and
• 20:53
  Speaker 3: kind of thinking about that balance. So there's still like
• 20:55
  Speaker 3: a need to think about diet and exercise, even if
• 20:59
  Speaker 3: the GLP-1 is acting, I will say I was at
• 21:03
  Speaker 3: an influencer dinner at some point a few months ago
• 21:06
  Speaker 3: and get into the economy later. But I think restaurants
• 21:08
  Speaker 3: have really adapted to this because all they serve was protein.
• 21:12
  Speaker 3: Like it was just exclusively protein. There was like one
• 21:15
  Speaker 3: tiny thing of French fries on the table.
• 21:17
  Speaker 1: And like, I like carbs. Yes.
• 21:20
  Speaker 2: You're a carb queen.
• 21:21
  Speaker 1: I was sad. I was sad about it. I was like, where's,
• 21:25
  Speaker 1: where's the bread service? But The bread service is over
• 21:28
  Speaker 1: at fancy restaurants.
• 21:29
  Speaker 2: Yeah, yeah. It's just egg white service now and protein water.
• 21:32
  Speaker 1: Tuna and egg whites exclusively.
• 21:36
  Speaker 2: Okay.
• 21:36
  Speaker 1: So that is the kind of, I think, big picture.
• 21:39
  Speaker 3: Of like sort of what happens initially when people are
• 21:42
  Speaker 3: on this and what are some of the other things
• 21:43
  Speaker 3: it could work for. I think we should get into
• 21:46
  Speaker 3: the things that people raise about that are more concerning.
• 21:51
  Speaker 1: The first of which is weight regain. The question of,
• 21:54
  Speaker 1: do I need to be on this forever?
• 21:55
  Speaker 2: Yeah.
• 21:56
  Speaker 3: And I will say in the trials, the evidence is
• 22:00
  Speaker 3: pretty sharp that when you put someone on a GLP-1,
• 22:03
  Speaker 3: they lose 20% of their body weight. You take them
• 22:05
  Speaker 3: off their GLP-1, they gain back about half of their
• 22:09
  Speaker 3: body weight, at.
• 22:10
  Speaker 1: Least in the trials.
• 22:11
  Speaker 3: So is this a sort of, is this a life sentence?
• 22:15
  Speaker 1: And is that a problem, I guess, is my secondary question.
• 22:18
  Speaker 2: I think the data is quite clear. But part of
• 22:24
  Speaker 2: me as a doctor is like, well, we have lots
• 22:25
  Speaker 2: of medications like this. When I treat someone for hypertension
• 22:28
  Speaker 2: and I put them on a blood pressure pill, in general,
• 22:32
  Speaker 2: the expectation is like, yeah, if you stop this blood
• 22:34
  Speaker 2: pressure pill, your blood pressure will go up again. There
• 22:38
  Speaker 2: is some constitutive effect there. One of the things I've
• 22:41
  Speaker 2: seen online from influencers, though, who are kind of anti-GLP-1s
• 22:45
  Speaker 2: is like, oh, but if you lose weight through lifestyle
• 22:48
  Speaker 2: change and changing your habits, then you'll have that forever.
• 22:53
  Speaker 2: But with GLP-1, you're stuck for life. And you know
• 22:56
  Speaker 2: this data as well as I do, Emily. It's the
• 22:57
  Speaker 2: stupidest thing I've ever heard.
• 22:58
  Speaker 1: Yeah.
• 23:00
  Speaker 2: Like the data on maintaining weight loss with diet is abysmal.
• 23:06
  Speaker 1: Literally awful.
• 23:07
  Speaker 2: Dismal. Is abysmal.
• 23:10
  Speaker 3: This is for me like the stupidest piece of this
• 23:13
  Speaker 3: discussion because it sort of presumes like– well, of course
• 23:17
  Speaker 3: we had a way before for people to lose large
• 23:20
  Speaker 3: amounts of weight and keep it off with diet. And now,
• 23:23
  Speaker 3: you know, we're not using that anymore. It's like, actually, no, you, yes,
• 23:26
  Speaker 3: it is possible to lose weight with diet. And some
• 23:28
  Speaker 3: people do. And I know because they show up in
• 23:30
  Speaker 3: comments when I talk about this and they're like, I
• 23:32
  Speaker 3: lost 300 pounds doing yoga and walking around the block
• 23:35
  Speaker 3: one time. And it's like, that's super for you. But
• 23:37
  Speaker 3: for most people that actually isn't effective. Most diets work
• 23:42
  Speaker 3: for a little while and then people gain the weight back.
• 23:44
  Speaker 3: It's very, very consistent. And so I'm not sure this
• 23:48
  Speaker 3: is really any different than that, nor do I think
• 23:51
  Speaker 3: it's very different, as you say, than something like a statin,
• 23:54
  Speaker 3: which people go on and then they stay on forever,
• 23:56
  Speaker 3: and which, by the way, you might be able to
• 23:58
  Speaker 3: get off after you're on your GLP-1 because your cholesterol
• 24:01
  Speaker 3: might improve.
• 24:02
  Speaker 1: So that's another thing to think about.
• 24:03
  Speaker 2: Well, yeah, I was thinking the same thing with my
• 24:05
  Speaker 2: blood pressure pill. I was like, actually, they might be
• 24:07
  Speaker 2: able to come off if they start the GLP-1. The trials,
• 24:10
  Speaker 2: one of the reasons we even have this data is
• 24:12
  Speaker 2: because most of these trials last basically a year. Some
• 24:16
  Speaker 2: go out to a year and three months or so,
• 24:18
  Speaker 2: but that's the extent of the data. We just don't
• 24:22
  Speaker 2: know with that degree of fidelity what 10 years on
• 24:26
  Speaker 2: a GLP-1 in terms of weight loss looks like. There's
• 24:29
  Speaker 2: observational data to that effect because the GLP-1s have been
• 24:31
  Speaker 2: around for so long, but the randomized trial data is
• 24:34
  Speaker 2: limited in scope. What is interesting is is how people
• 24:39
  Speaker 2: in the real world are kind of handling this. So yes,
• 24:41
  Speaker 2: they lose a lot of weight, they get to a
• 24:43
  Speaker 2: weight they're happy with, and then they're like, okay, I'm good.
• 24:47
  Speaker 2: And what I've found... with patients that I've spoken to
• 24:50
  Speaker 2: is generally not like, okay, I'm going off GLP-1, but
• 24:52
  Speaker 2: people are doing this thing that often gets, that's called microdosing.
• 24:57
  Speaker 2: So what do we know about microdosing? Is this the answer? Like, yeah,
• 25:00
  Speaker 2: you'll be on it, but you're only going to be
• 25:01
  Speaker 2: on a little bit.
• 25:02
  Speaker 3: I don't think we have any idea. And I think
• 25:03
  Speaker 3: the reason is sort of interesting in terms of the science. So,
• 25:07
  Speaker 3: you know, think about the kind of, who is running
• 25:10
  Speaker 3: the trials of these? The people who are running the
• 25:11
  Speaker 3: trials are the people who are making the drugs, right? Novonordis,
• 25:14
  Speaker 3: Gilae Lily, the makers of the drugs run the trials.
• 25:18
  Speaker 3: And they trial their drug at the dosage that they
• 25:22
  Speaker 3: are going to sell it at because that is what
• 25:24
  Speaker 3: the FDA tells them to do.
• 25:26
  Speaker 1: That's how drug trials work.
• 25:28
  Speaker 3: They don't usually run trials of like, and here's exactly
• 25:32
  Speaker 3: how you're going to do it in the real world.
• 25:35
  Speaker 3: But in the real world, when people get to this,
• 25:37
  Speaker 3: most of the doctors I know who are using this
• 25:40
  Speaker 3: will do, I'm not sure they'd call it microdosing. They
• 25:41
  Speaker 3: call it a maintenance dose, right? That we are like,
• 25:44
  Speaker 3: we start with a low dose. We go up to
• 25:45
  Speaker 3: a dose in which you're losing weight in a consistent way.
• 25:48
  Speaker 3: You get to the weight that you would like to be,
• 25:50
  Speaker 3: and then you drop down the dosage until you get
• 25:53
  Speaker 3: to a point where you are maintaining that weight and
• 25:56
  Speaker 3: that feels comfortable. And that's how this is actually operating
• 25:59
  Speaker 3: for most people in the real world. I'm not sure
• 26:02
  Speaker 3: we're going to see trials of that. in the short run,
• 26:05
  Speaker 3: because I'm not sure who would run them, right? So
• 26:07
  Speaker 3: I don't think Novo Nordisk is going to run that
• 26:09
  Speaker 3: kind of trial. Somebody will eventually, but I think it's,
• 26:12
  Speaker 3: and it's also just so like, in ideal world, it's
• 26:14
  Speaker 3: sort of so titrated. One of the concerns I think
• 26:17
  Speaker 3: is that people are titrating it themselves, whereas a much
• 26:20
  Speaker 3: better thing would be to titrate under the supervision of
• 26:22
  Speaker 3: your doctor, not to just like take half your dose,
• 26:24
  Speaker 3: which is my sense is what.
• 26:27
  Speaker 2: Right. And a lot of this has to be done
• 26:29
  Speaker 2: actually through compounding pharmacies, which we've talked about in a
• 26:32
  Speaker 2: prior episode, has potential safety concerns. The Ozempic pen has
• 26:38
  Speaker 2: a little clicky dial that you can turn, which does
• 26:40
  Speaker 2: allow you to change dose. Um, my understanding is that
• 26:44
  Speaker 2: the ZEP bound pen does not. So the only way
• 26:47
  Speaker 2: to kind of microdose that is to break the thing
• 26:49
  Speaker 2: open and like, don't do that. That's, that's a bad idea.
• 26:52
  Speaker 2: So you're kind of going outside the box a little
• 26:55
  Speaker 2: bit here, but I agree. I think this is probably
• 26:58
  Speaker 2: what happens. Like, like eventually we'll get to a point where,
• 27:02
  Speaker 2: first of all, there'll be oral drugs. And this will
• 27:04
  Speaker 2: be the kind of thing that you do probably take
• 27:07
  Speaker 2: some lowish dose probably for an extended period of time
• 27:10
  Speaker 2: unless you want to gain some more weight.
• 27:13
  Speaker 1: Okay.
• 27:13
  Speaker 3: So it is a long-term medication, but maybe the right
• 27:16
  Speaker 3: frame is this is a long-term medication like you're sat
• 27:18
  Speaker 3: in your blood pressure medication and not a diet like
• 27:22
  Speaker 3: the time that you tried to lose weight on the
• 27:23
  Speaker 3: all-protein diet for six months and then gained it back,
• 27:26
  Speaker 3: which is, in fact, how people interact with diets.
• 27:30
  Speaker 1: Okay. The second big concern is just, are there side effects?
• 27:33
  Speaker 1: Which there are. I think it should be very clear.
• 27:35
  Speaker 1: Like this is a drug. It has side effects.
• 27:38
  Speaker 3: The main side effect people complain about is nausea and
• 27:42
  Speaker 3: other gastric problems. That is a, I think I've just,
• 27:47
  Speaker 3: that's a feature. I don't know if it's a feature
• 27:49
  Speaker 3: or a bug. It's a very common side effect. What
• 27:53
  Speaker 3: about Some of these more serious things, pancreatitis, depression.
• 28:00
  Speaker 2: Okay. Probably should go through very quickly, like one by one. Pancreatitis, yes.
• 28:06
  Speaker 2: Rare case reports probably associated with these drugs. We know
• 28:10
  Speaker 2: they act on the pancreas. In fact, that Gila monster venom,
• 28:12
  Speaker 2: when a Gila monster bites a mouse, it causes an
• 28:15
  Speaker 2: acute pancreatitis. So I buy it. Yes. Rarely, but yes.
• 28:19
  Speaker 2: So people need to know symptoms of that are a
• 28:22
  Speaker 2: deep and painful burning in your upper part of your stomach.
• 28:27
  Speaker 2: You'll know this is bad when it's happening. You definitely
• 28:30
  Speaker 2: want to get checked out. Okay, the depression suicide thing.
• 28:34
  Speaker 2: This is really interesting because we've talked already about the
• 28:38
  Speaker 2: ability of these drugs to potentially modulate reward pathways in
• 28:41
  Speaker 2: the brain. You framed it differently, Emily, for the first time.
• 28:45
  Speaker 2: I'm still kind of grappling with the way you frame this.
• 28:48
  Speaker 2: The way I hear people frame this is like, oh,
• 28:50
  Speaker 2: it takes away your desire to eat. It takes away
• 28:52
  Speaker 2: your desire to smoke. It takes away your desire to
• 28:55
  Speaker 2: drink alcohol. What it's doing is it's kind of all
• 28:58
  Speaker 2: the pleasurable things that your brain wants. It just kind
• 29:02
  Speaker 2: of cuts that off and then like, are you joyless?
• 29:05
  Speaker 2: Is there no hope in the world? And if so,
• 29:07
  Speaker 2: might it not increase depression and suicidality? RFK Jr. himself
• 29:12
  Speaker 2: has raised this issue. And I will just point out
• 29:15
  Speaker 2: that the current best data is from a meta-analysis of
• 29:18
  Speaker 2: 27 randomized controlled trials, including 32,000 people looking at the
• 29:23
  Speaker 2: rates of suicide and self-harm from these drugs. And there
• 29:27
  Speaker 2: is no difference in suicide or self-harm events between placebo
• 29:31
  Speaker 2: and and these drugs. So I do not think that
• 29:33
  Speaker 2: is real. And one of the reasons, like the way
• 29:36
  Speaker 2: you've reframed this for me is as opposed to saying like, oh,
• 29:40
  Speaker 2: it cuts the reward pathways. Like you don't get the
• 29:42
  Speaker 2: like high of eating food or the high of drinking alcohol.
• 29:46
  Speaker 2: You've reframed it as like, it's not ending that thing.
• 29:49
  Speaker 2: It's giving you this like, um, it's giving you control.
• 29:52
  Speaker 2: It's giving you more focus, which is, I kind of
• 29:54
  Speaker 2: like that. I mean, I don't know if it's true,
• 29:56
  Speaker 2: but that is a different way to think about it
• 29:57
  Speaker 2: that might explain why you get less drinking, but not suicidality.
• 30:02
  Speaker 1: Yeah. I don't know.
• 30:03
  Speaker 3: I mean, I think that is a way that I
• 30:05
  Speaker 3: have heard people try to describe to me what this
• 30:08
  Speaker 3: is like, which I think is a potentially interesting organization
• 30:11
  Speaker 3: of some of these facts.
• 30:13
  Speaker 1: But I don't know. Again, it's like it's always hard
• 30:16
  Speaker 1: to get inside people's brains.
• 30:17
  Speaker 3: It is.
• 30:18
  Speaker 2: When we talk about enjoyable things that your brain likes
• 30:21
  Speaker 2: to do, something that always comes up is sex. So
• 30:25
  Speaker 2: what do we know about sexual effects of these drugs?
• 30:28
  Speaker 1: Relatively little.
• 30:31
  Speaker 3: You know, there are people who will say like this
• 30:34
  Speaker 3: limits your desire to have sex. I don't think there's
• 30:38
  Speaker 3: a lot of evidentiary support for that. What I will
• 30:42
  Speaker 3: say is there are some real issues that, you know,
• 30:46
  Speaker 3: people in long-term relationships grapple with when they go on
• 30:48
  Speaker 3: these medications, particularly if, you know, the New York Times
• 30:53
  Speaker 3: actually said a series of very interesting stories about couples
• 30:58
  Speaker 3: where one person has gone on a GLP-1 and they
• 31:00
  Speaker 3: sort of said, well, you know, our life used to
• 31:02
  Speaker 3: revolve around going out to dinner and, you know, drinking
• 31:05
  Speaker 3: together and hanging out and like, and now this person
• 31:07
  Speaker 3: doesn't want to do those things anymore.
• 31:09
  Speaker 1: And so, you know, maybe you.
• 31:11
  Speaker 3: you do want to have sex, maybe you don't want
• 31:12
  Speaker 3: to have sex, but there's another piece of, it's not
• 31:16
  Speaker 3: about a lack of interest in a physical relationship, or
• 31:19
  Speaker 3: maybe it is, but it's also about changing the relationship.
• 31:22
  Speaker 3: And I actually think that's a really important part of
• 31:25
  Speaker 3: this for a lot of people, that eating is a
• 31:27
  Speaker 3: huge part of our lives. And if you change things
• 31:31
  Speaker 3: so you aren't going to eat in the same way,
• 31:35
  Speaker 3: And you are in a relationship with another person and
• 31:37
  Speaker 3: they're not going to change that.
• 31:40
  Speaker 1: And your body is going to be going through a
• 31:41
  Speaker 1: lot of changes.
• 31:41
  Speaker 3: Like that is just an adaptation that people should expect
• 31:45
  Speaker 3: and should, you know, think about as part of this.
• 31:49
  Speaker 3: I think it's less about sex and more just about,
• 31:52
  Speaker 3: you know, when you change something totally about yourself and
• 31:55
  Speaker 3: your relationship, it changes and you have to adapt and
• 31:57
  Speaker 3: relationships are hard is my fundamental feeling.
• 32:00
  Speaker 2: Yeah, indeed. I agree. There's sort of a disturbing lack
• 32:03
  Speaker 2: of data on this. As I was looking in, I'll
• 32:06
  Speaker 2: just say there are like 10 times as many studies
• 32:10
  Speaker 2: on male impotence and anorgasmia from GLP-1s than there is
• 32:17
  Speaker 2: on female. It's like, all right, researchers, get with the
• 32:19
  Speaker 2: program here a little bit. Women are more likely to
• 32:22
  Speaker 2: take GLP-1s and are more likely to lose a greater
• 32:25
  Speaker 2: percentage of body weight on GLP-1s than men. Clearly, this
• 32:27
  Speaker 2: needs to be looked into.
• 32:28
  Speaker 3: I agree.
• 32:29
  Speaker 2: There's nothing terribly compelling. I did find one study that
• 32:34
  Speaker 2: was an observational study looking at rates of a clinical
• 32:37
  Speaker 2: diagnosis of anorgasmia, the inability to have an orgasm, which
• 32:42
  Speaker 2: did find that compared to women not on GLP-1s. Those
• 32:45
  Speaker 2: on GLP-1s had that diagnosis code about twofold more often.
• 32:49
  Speaker 2: It's a very rare diagnosis code to get because most
• 32:52
  Speaker 2: people don't talk about this with their doctor in the
• 32:53
  Speaker 2: first place. But that rate was similar to women taking metformin,
• 32:56
  Speaker 2: which is another drug for diabetes. So this is probably
• 33:00
  Speaker 2: related to the underlying reason that the woman is taking
• 33:03
  Speaker 2: the GLP-1 as opposed to the GLP-1 itself. But, you know,
• 33:08
  Speaker 2: more data. I'd like more data here.
• 33:10
  Speaker 3: Who doesn't want more data on women's sexual function as
• 33:12
  Speaker 3: opposed to men's sexual function.
• 33:13
  Speaker 1: Where really we're good. Thanks. It's enough data. We know everything.
• 33:17
  Speaker 1: We got it. We're fine.
• 33:19
  Speaker 3: OK, I think there are some interesting social and like
• 33:22
  Speaker 3: regulatory questions here or maybe just social questions that we
• 33:26
  Speaker 3: should make sure that we hit on. Last thing that
• 33:30
  Speaker 3: I will say I'm bringing up in part because this
• 33:32
  Speaker 3: is the first thing my father ever asked me about Ozempic.
• 33:35
  Speaker 1: He was like, have you heard of Ozempic Face? And
• 33:38
  Speaker 1: then he was like, blah, blah, blah, person that I
• 33:40
  Speaker 1: know has it. And I'm like, yes, I have heard
• 33:43
  Speaker 1: of that. So Perry, have you heard of Ozempic Face?
• 33:48
  Speaker 2: No. Oh, I've heard of ozempic face. I've heard of
• 33:50
  Speaker 2: ozempic butt.
• 33:52
  Speaker 1: Yeah. Yeah.
• 33:54
  Speaker 3: So ozempic face, my sense is that when you lose weight,
• 33:57
  Speaker 3: your skin takes some time to tighten back up, which,
• 34:02
  Speaker 3: or maybe it doesn't tighten back up and that you
• 34:05
  Speaker 3: lose a lot of weight in your face then, or
• 34:08
  Speaker 3: your butt, it will be saggy. Yep.
• 34:11
  Speaker 1: Doesn't matter if it's on a GLP-1 or in some
• 34:13
  Speaker 1: other way.
• 34:14
  Speaker 2: Yeah. We don't have that magic bullet that only makes
• 34:17
  Speaker 2: you lose fat around your belly but leaves shredded abs behind.
• 34:21
  Speaker 2: When you lose weight, your body consumes fat. Fat is
• 34:24
  Speaker 2: there to be a source of energy when you don't
• 34:27
  Speaker 2: take in enough calories, and that's what GLP-1s do. They
• 34:30
  Speaker 2: make you eat less, so you expend more calories. than
• 34:33
  Speaker 2: you're consuming. And so your body breaks down fat, as
• 34:36
  Speaker 2: well as some other tissues, as we discussed, to recapture
• 34:40
  Speaker 2: that energy. And it'll take fat from everywhere. What ozempic
• 34:42
  Speaker 2: face is, medically speaking, is mid-face volume loss. That's what
• 34:46
  Speaker 2: the plastic surgeons call it. So that's sort of cheekbones
• 34:50
  Speaker 2: and cheeks. Gives kind of a sunken appearance. And you're right.
• 34:54
  Speaker 2: This is what happens with all form. Yep.
• 34:57
  Speaker 1: But that one is social.
• 34:58
  Speaker 2: Emily, for those of you just listening on the podcast,
• 35:00
  Speaker 2: is making kind of a fish face. This is what
• 35:03
  Speaker 2: happens with all forms of weight loss. I think the
• 35:06
  Speaker 2: reason it's in the zeitgeist now is that we just
• 35:08
  Speaker 2: never had effective weight loss that was working for the masses.
• 35:12
  Speaker 2: So where you will have seen this before is people
• 35:15
  Speaker 2: getting gastric bypass surgery, which was like before– The JLP1s
• 35:19
  Speaker 2: was the main way that people could lose a significant
• 35:21
  Speaker 2: amount of body weight, but that's a big surgery. But
• 35:23
  Speaker 2: if you think of like Al Roker, before and after
• 35:26
  Speaker 2: he had gastric bypass, before and after that, he looked
• 35:29
  Speaker 2: very different. He had mid-face volume loss. We didn't call
• 35:32
  Speaker 2: it a zempic face back then because it didn't exist.
• 35:34
  Speaker 2: This is just weight loss face. It is real. In fact,
• 35:38
  Speaker 2: the American Academy of Facial Plastic and Reconstructive Surgeons reported
• 35:42
  Speaker 2: a 50% increase in facial fat grafting procedures in 2024.
• 35:47
  Speaker 2: So people are thinking about it.
• 35:49
  Speaker 1: Totally. Okay.
• 35:50
  Speaker 3: I think that's a really good segue because I am
• 35:53
  Speaker 3: very interested in a knock on economic effects of these medications.
• 35:57
  Speaker 2: Oh, I love when you bring your economic doctorate into
• 36:01
  Speaker 2: this discussion. What's going to happen?
• 36:02
  Speaker 1: So I'm going to tell you- And where do I invest? Okay.
• 36:05
  Speaker 3: So if I were an investor, I will tell you,
• 36:07
  Speaker 3: number one, I would invest in places that do excess
• 36:11
  Speaker 3: skin removal.
• 36:12
  Speaker 1: I'm not kidding. I think that there is going to
• 36:14
  Speaker 1: be a huge.
• 36:15
  Speaker 3: Excess demand for skin removal procedures because if people have
• 36:20
  Speaker 3: been overweight for a very long time and you lose,
• 36:22
  Speaker 3: if you lose 300 pounds a you end up with
• 36:25
  Speaker 3: a lot more skin and people can find it. They
• 36:29
  Speaker 3: may not like how it looks, but also it can
• 36:31
  Speaker 3: be uncomfortable and difficult to navigate. And there are procedures
• 36:35
  Speaker 3: that will remove excess skin. And I think that that
• 36:37
  Speaker 3: is incredible growth area. And we will see a growth
• 36:41
  Speaker 3: in the kind of like med spa skin removal surgery situations.
• 36:47
  Speaker 2: Okay. Those are big surgeries. That's no joke.
• 36:49
  Speaker 1: I realize that, but I'm still going to go for
• 36:53
  Speaker 1: investing there. Okay. So that's one place.
• 36:56
  Speaker 2: I'm wondering about our food industrial complex, right? I walk
• 36:59
  Speaker 2: down this supermarket and there's like 80 different cereals. Are
• 37:03
  Speaker 2: they scary? Is Kellogg's like, uh-oh?
• 37:05
  Speaker 1: I think they are. Yeah.
• 37:06
  Speaker 3: So I think there's like two interesting sort of places
• 37:08
  Speaker 3: that may be affected by this. One is like the
• 37:11
  Speaker 3: snack food complex, right? If you think about what is
• 37:14
  Speaker 3: going to go from people's meals, I think snacks are
• 37:17
  Speaker 3: likely to go some. And so I think we are
• 37:20
  Speaker 3: already seeing impacts on snack foods. We're already seeing restaurants
• 37:25
  Speaker 3: think about, hey, can we lower the portion sizes, right?
• 37:28
  Speaker 1: Like for a restaurant, that's good.
• 37:29
  Speaker 3: You'd rather give people smaller portions because it's you know,
• 37:32
  Speaker 3: less expensive for you. And so we sort of, I
• 37:34
  Speaker 3: think we may see a little shrinking. The place I
• 37:38
  Speaker 3: think the, the other, the growth area in the other
• 37:40
  Speaker 3: direction is protein snacks, right? If you think all of
• 37:42
  Speaker 3: a sudden people are eating fewer calories, but they need
• 37:44
  Speaker 3: a lot of protein, that's where you need your, your protein, popcorn,
• 37:48
  Speaker 3: your protein.
• 37:50
  Speaker 2: I'm so glad there wasn't enough protein snacks.
• 37:54
  Speaker 1: There weren't enough protein snacks. And now the David bar
• 37:57
  Speaker 1: is coming for you.
• 37:58
  Speaker 3: And so I think it's a sort of protein growth,
• 38:00
  Speaker 3: carbohydrate snack decline. And so I do think that there's
• 38:04
  Speaker 3: some movement in that space. I'm not exactly sure how
• 38:07
  Speaker 3: I would invest on that or on any of my ideas.
• 38:10
  Speaker 3: It's a good thing I don't have a lot of
• 38:11
  Speaker 3: money to invest in my stupid investment ideas.
• 38:14
  Speaker 2: What about medicine with a capital M? Like, I work
• 38:19
  Speaker 2: in a hospital. I see patients in a clinic. Do
• 38:22
  Speaker 2: you think that this can be transformative enough that, like,
• 38:25
  Speaker 2: I won't have as many kidney disease patients? I won't
• 38:27
  Speaker 2: have as many heart disease patients? I mean, people have
• 38:29
  Speaker 2: to die of something, I guess, right? Like, eventually, maybe
• 38:32
  Speaker 2: it happens when they're older.
• 38:33
  Speaker 3: Yeah, I mean, those are much slower moving changes. I
• 38:37
  Speaker 3: think there's an interesting overlap there. with the question of
• 38:42
  Speaker 3: kind of the cost of these drugs. So these drugs
• 38:44
  Speaker 3: are right now quite expensive. The prices have been coming
• 38:47
  Speaker 3: down a lot, but they're still expensive. They're covered in
• 38:50
  Speaker 3: sometimes intermittently by insurance.
• 38:52
  Speaker 1: But one of the arguments for expansion.
• 38:56
  Speaker 3: Of access to these medications, especially if we think about
• 38:59
  Speaker 3: like a government payer, is that they will lower people's
• 39:02
  Speaker 3: risk of other things.
• 39:04
  Speaker 1: So, you know, you, Perry, are expensive.
• 39:06
  Speaker 3: Somebody comes to see you, you know, it costs money.
• 39:09
  Speaker 3: If fewer people have kidney disease because of their GLP-1s,
• 39:12
  Speaker 3: that actually sort of offsets the cost of the GLP-1
• 39:15
  Speaker 3: to some extent.
• 39:16
  Speaker 1: And depending on how big those effects are, we could
• 39:20
  Speaker 1: see these medications, even though they are relatively expensive, and
• 39:24
  Speaker 1: even if they stayed relatively expensive, we could see them, like,
• 39:27
  Speaker 1: cause overall cost savings in the healthcare market. which would
• 39:31
  Speaker 1: be in part.
• 39:31
  Speaker 3: Of reduction in sort of need for doctors, but probably
• 39:34
  Speaker 3: would be more significantly a reduction in use of other medications.
• 39:38
  Speaker 3: So if you are a maker of a statin, this
• 39:41
  Speaker 3: may be sort of more bad for you than if
• 39:44
  Speaker 3: you are someone who treats people with a heart attack,
• 39:46
  Speaker 3: which is still something people are going to die of.
• 39:48
  Speaker 1: Just maybe they'll die of them later.
• 39:51
  Speaker 2: One of the things that this ties into is, okay,
• 39:55
  Speaker 2: we've sort of come to the point where we're like,
• 39:57
  Speaker 2: These drugs are going to be in the fabric of
• 39:59
  Speaker 2: our society, whether they're injectable or oral. We've said that
• 40:02
  Speaker 2: you're going to be potentially taking them for, in some
• 40:05
  Speaker 2: form or another, for a long period of time. And
• 40:08
  Speaker 2: a lot of people are worried about that saying like,
• 40:11
  Speaker 2: you know, but we don't know what might happen, right?
• 40:14
  Speaker 2: That sure, they seem to be working great now, but
• 40:17
  Speaker 2: how do we know that if you're not on it
• 40:18
  Speaker 2: for 30 years, it causes cancer or something like that?
• 40:21
  Speaker 2: What data do we have to either reassure people or
• 40:24
  Speaker 2: terrify them?
• 40:24
  Speaker 3: Yeah, I mean, I think that the short answer is
• 40:27
  Speaker 3: we can't really fully reassure people about that. You know,
• 40:30
  Speaker 3: these first, when you said at the top, the first
• 40:31
  Speaker 3: of these drugs was approved in 2005. People have been
• 40:34
  Speaker 3: on this for diabetes for a long time. We haven't
• 40:36
  Speaker 3: seen those kind of signals, but it's not exactly the
• 40:39
  Speaker 3: same drugs. It's not the same dosing levels, not for
• 40:41
  Speaker 3: the same indication. So, you know, if you want to
• 40:44
  Speaker 3: know what is the impact of these drugs in 30 years,
• 40:46
  Speaker 3: you need to wait for 30 years. And we ultimately,
• 40:49
  Speaker 3: like with almost any new drug, you've got to weigh
• 40:54
  Speaker 3: the sort of known value of the medication against these
• 40:58
  Speaker 3: kind of long-term potential risks. I actually think that sort
• 41:02
  Speaker 3: of cost-benefit calculation is always an important part of these choices,
• 41:06
  Speaker 3: but it is probably relevant to the extent that some
• 41:09
  Speaker 3: of the usage of these medications is not for indicated purposes, right?
• 41:15
  Speaker 3: So we are definitely seeing use of GLP-1s in populations
• 41:20
  Speaker 3: where people do not need them to treat metabolic disease, right?
• 41:23
  Speaker 1: This is a medication that is intended to treat.
• 41:26
  Speaker 3: Obesity or diabetes or complications of obesity. That is the
• 41:30
  Speaker 3: indication for the medication. It's not a medication intended to
• 41:35
  Speaker 3: move your BMI from 21 to 14 or 17, which
• 41:40
  Speaker 3: is some of how it seems like it's being used,
• 41:43
  Speaker 3: particularly you know, in celebrity circles, and it's always hard
• 41:46
  Speaker 3: to know who's losing weight for what reason, but there's
• 41:48
  Speaker 3: a kind of, the part of the cautionary conversation, it
• 41:52
  Speaker 3: feels important to me, is the one where people are
• 41:55
  Speaker 3: sort of using these effectively really off-label in a way
• 42:00
  Speaker 3: that changes the conversation around what is an appropriate physical
• 42:05
  Speaker 3: appearance for someone, and we're kind of, we lost a
• 42:08
  Speaker 3: little bit of what I thought was probably a good
• 42:11
  Speaker 3: move towards the idea that, you know, people could be
• 42:14
  Speaker 3: different sizes and not just a size two.
• 42:18
  Speaker 2: Thank you for saying that. It's worth noting that fat
• 42:23
  Speaker 2: has value. It is metabolically important. It is hormonally active
• 42:28
  Speaker 2: tissue in a good way. And being underweight, however you
• 42:33
  Speaker 2: get to being underweight with this drug or any other way,
• 42:37
  Speaker 2: can have actual long-term health consequences. And there's, there's any
• 42:41
  Speaker 2: number of studies that actually show that sort of the
• 42:44
  Speaker 2: sweet spot for body weight in terms of longevity and
• 42:48
  Speaker 2: especially resilience against disease. So when you do get sick,
• 42:52
  Speaker 2: you know, being able to sort of bounce back from
• 42:54
  Speaker 2: that is probably in the, what we see, you know,
• 42:56
  Speaker 2: the normal weight range, you know, a BMI between 20
• 42:59
  Speaker 2: and 25 or so, if you're pushing below that, you
• 43:02
  Speaker 2: are starting to stress your body a little bit more.
• 43:05
  Speaker 2: I just have to say, I have a patient who
• 43:07
  Speaker 2: is telling me that she was taking one of these
• 43:09
  Speaker 2: drugs to get back to her original weight. And I said,
• 43:11
  Speaker 2: what was your original weight? And she said, seven pounds,
• 43:14
  Speaker 2: 14 ounces. That's too much.
• 43:17
  Speaker 3: No, I mean, I will say I've started to see discussion,
• 43:19
  Speaker 3: you know, people are, I've started to talk about this
• 43:22
  Speaker 3: a lot in the like endurance sports community, because it
• 43:25
  Speaker 3: is of course true if you are like a runner,
• 43:28
  Speaker 3: that there is some value to being smaller because you're
• 43:33
  Speaker 3: moving less bulk and But actually, these medications are really
• 43:37
  Speaker 3: bad for performance.
• 43:38
  Speaker 1: And some of these sort.
• 43:40
  Speaker 3: Of discussions, I think, have gotten like a little confused
• 43:43
  Speaker 3: and also ultimately probably not very good for either people's
• 43:47
  Speaker 3: health or in that particular case for running fast.
• 43:51
  Speaker 1: So if you want to run fast, this is maybe
• 43:53
  Speaker 1: not for you.
• 43:54
  Speaker 2: Not for everyone.
• 43:55
  Speaker 1: Not for everyone. Yeah. All right.
• 43:57
  Speaker 3: So Perry, before we get to our final feelings on this,
• 43:59
  Speaker 3: let's talk about sort of where this is going and
• 44:02
  Speaker 3: both in terms of the medications and in terms of,
• 44:04
  Speaker 3: of kids. So on the question of the medications, you know,
• 44:08
  Speaker 3: my sense is we're just going to keep seeing new
• 44:11
  Speaker 3: versions of this come out that are, you know, better
• 44:13
  Speaker 3: in a variety of dimensions, easier to dose oral versus injected,
• 44:18
  Speaker 3: more weight loss in 28% versus 20%.
• 44:21
  Speaker 1: Those are the two big dimensions. What, what other dimensions
• 44:24
  Speaker 1: are we going to see innovation?
• 44:25
  Speaker 2: Cost, things will get cheaper. But yeah, honestly, I think
• 44:29
  Speaker 2: in terms of weight loss, up at 28%, I think
• 44:32
  Speaker 2: we're done. You're taking a 200-pound person and bringing them
• 44:36
  Speaker 2: down to 140 pounds. I don't think we need to
• 44:39
  Speaker 2: improve too much on that. So yeah, you're going to
• 44:41
  Speaker 2: see cost differences as things come off patent, and then
• 44:44
  Speaker 2: the orals are going to be somewhat game-changing. And there
• 44:47
  Speaker 2: may be tweaks that improve side effect profile and things
• 44:50
  Speaker 2: like that. We'll see that. The question of kids is
• 44:55
  Speaker 2: really fascinating. So the landscape right now is that Ozempic
• 44:59
  Speaker 2: itself does have FDA approval for kids 12 and up.
• 45:03
  Speaker 2: It's the only one. The rest start at age 18.
• 45:07
  Speaker 2: I'm ambivalent about this because, for one thing, kids are kids.
• 45:11
  Speaker 2: They're not just small adults. They're their own things. They're
• 45:14
  Speaker 2: growing and growing. Especially for kids who are growing, calories
• 45:18
  Speaker 2: are important for that. And stunting a kid's growth is
• 45:20
  Speaker 2: a permanent thing that can happen. So I'm very nervous
• 45:23
  Speaker 2: about this. On the other hand, there is an argument
• 45:27
  Speaker 2: to be said that the fat tissue that you add
• 45:31
  Speaker 2: as a child does not really go away ever. In fact,
• 45:36
  Speaker 2: as you lose weight, a lot of those cells are
• 45:38
  Speaker 2: just shrinking, not necessarily dying off or evaporating. Is it
• 45:43
  Speaker 2: a possibility that establishing some habits with the use of
• 45:47
  Speaker 2: a drug like this in your youth when you're sort
• 45:49
  Speaker 2: of forming your relationship with food could be beneficial in
• 45:52
  Speaker 2: the long term? Or on the other hand, could it
• 45:54
  Speaker 2: be entirely harmful? Like I am really up in the
• 45:56
  Speaker 2: air about this.
• 45:57
  Speaker 1: You're in a rabbit hole. Yeah, me too.
• 45:59
  Speaker 3: I am.
• 46:00
  Speaker 2: I like don't– I don't know.
• 46:01
  Speaker 3: I think it's really complicated because you're right. I think
• 46:03
  Speaker 3: our habits, our taste for foods, our form when we
• 46:06
  Speaker 3: are kids and that is– an argument for forming those habits. Well,
• 46:10
  Speaker 3: I mean, I guess my, the thing I would say
• 46:12
  Speaker 3: for sure is this should not be a first line.
• 46:14
  Speaker 3: Like I would really like us to think more carefully
• 46:20
  Speaker 3: about how we can help families develop good food habits
• 46:24
  Speaker 3: with their kids, whether that's like better school lunch programs,
• 46:27
  Speaker 3: better supports, or like all kinds of things I would
• 46:29
  Speaker 3: like to do before we get to like, let's ever
• 46:33
  Speaker 3: give everybody Ozempic when they're 12, which just feels like
• 46:37
  Speaker 3: probably there are some people who will benefit from that
• 46:39
  Speaker 3: and it'll be good to have that as an option,
• 46:41
  Speaker 3: but I don't want it to be the first line
• 46:44
  Speaker 3: and I don't think that that's a good idea.
• 46:47
  Speaker 1: Okay.
• 46:47
  Speaker 2: All right.
• 46:49
  Speaker 3: Okay, Perry, we're going to end with our segment in
• 46:52
  Speaker 3: which we give our yes or no, and I am
• 46:54
  Speaker 3: going to insist that we call this segment smash or pass.
• 46:58
  Speaker 1: All right.
• 46:59
  Speaker 2: I am on board. And for those of you from
• 47:01
  Speaker 2: a generation that is not X, you can Google what
• 47:04
  Speaker 2: that means.
• 47:05
  Speaker 1: All right. So Perry, GLP-1, smash or pass?
• 47:09
  Speaker 2: Smash. Definitely. Transformative drugs will be with us for a
• 47:14
  Speaker 2: long time, changing a lot of outcomes. Not for everyone,
• 47:17
  Speaker 2: as you say, but yeah, definite smash for me. How
• 47:19
  Speaker 2: about you?
• 47:20
  Speaker 3: Yeah, I'm a smash if it's the right person on
• 47:23
  Speaker 3: this one. I think for some people, for many people,
• 47:26
  Speaker 3: this is going to be a really game-changing solution. It's
• 47:28
  Speaker 3: not for everyone, but I think it's going to represent
• 47:31
  Speaker 3: a really important part of the health landscape in the
• 47:35
  Speaker 3: next several decades. Wellness Actually is produced in association with
• 47:42
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• 47:44
  Speaker 1: Our senior producer is Tamar Avishai.
• 47:46
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• 47:50
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• 48:12
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• 48:14
  Speaker 1: We'll let the influencers have the last word.
• 48:16
  Speaker 2: That's all commercial for Weight Watchers. We're doing GLP-1s now,
• 48:20
  Speaker 2: which is Ozempic and stuff. That's like a karate dojo
• 48:23
  Speaker 2: selling guns. You know what I mean? Like, it's not
• 48:27
  Speaker 2: what it is. The latest breakthrough in self-defense.
• 48:30
  Speaker 3: Guns!