In short
Podcast Episode Summary: What's the Deal with GLP-1s?
Podcast Title
Wellness, Actually
Hosts
Emily Oster & Perry Wilson, MD
Episode Description
In this episode, the hosts delve into GLP-1 medications, which have gained popularity for weight loss. They explore the origins of these drugs, their effectiveness, side effects, potential long-term impacts, and societal implications, including the effects on mental health and relationships.
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Key Highlights
- What are GLP-1s?
- GLP-1 (Glucagon-like peptide-1) medications are derived from the venom of the Gila monster, initially discovered for their effects on blood sugar regulation.
- Historical Context:
- Discovered in the 1970s, GLP-1 was studied for its ability to slow gastric emptying and promote satiety.
- The first GLP-1 drug, Exenatide (brand name Byetta), was FDA approved in 2005.
- Mechanism of Action
- GLP-1 medications work by mimicking human GLP-1, leading to reduced appetite and increased feelings of fullness.
- Newer variants have longer half-lives, allowing for weekly injections rather than daily.
- Effectiveness and Usage
- Current popular medications:
- Wegovy (semaglutide): Used for weight loss.
- Zepbound (trisepatide): Shows significant weight loss results.
- Efficacy: Many users experience 15-20% weight loss; some studies suggest up to 30% weight loss in a year.
- Concerns and Side Effects
- Common Side Effects: Nausea and gastrointestinal discomfort.
- Serious Side Effects:
- Potential risk for pancreatitis.
- Concerns regarding depression and changes in libido.
- Social Impact: Changes in social behaviors and relationships, including shifts in dining habits and lifestyle.
- Weight Maintenance and Regain
- Studies indicate that stopping GLP-1s may lead to regaining a portion of lost weight.
- Experts discuss the realities of needing long-term usage, similar to other chronic condition medications (i.e., statins, blood pressure meds).
- Long-Term Effects and Future Directions
- Ongoing research is needed to understand long-term safety and efficacy.
- Discussions about the potential economic impacts on healthcare, including reduced rates of obesity-related diseases.
- Ethical considerations around prescribing to younger populations.
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Key Takeaways
- Transformative Potential: These medications may revolutionize weight management and chronic disease treatment.
- Individual Variation: Not all individuals will respond positively; it's essential to personalize treatment.
- Mental and Social Implications: Users may experience changes in their mental health and interpersonal relationships due to alterations in lifestyle and self-image.
- Future of GLP-1s: New formulations, including oral medications and ongoing innovations, are expected to emerge.
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Conclusion Emily Oster and Perry Wilson stress the importance of understanding GLP-1s holistically, acknowledging both their potential benefits and challenges. As these medications become more integrated into healthcare, a nuanced approach to their use will be essential for maximizing positive outcomes while minimizing risks.
Written by AI. May contain mistakes. Listen to the episode to check what was said.
Chapters
Tap a time to open that second in VOUnderstanding GLP-1s
3:41 to 4:36
Discussion on the use of GLP-1 medications and their popularity.
“And some of it is, well, actually bullshit.”
Health News Roundup
5:25 to 11:40
Hosts discuss health news including RFK Jr.'s podcast appearance and Dr. Casey Means' confirmation hearing.
“If you could control the behavior of anybody around you, what kind of life would you have?”
Football Players and Neurocognitive Deficits
11:40 to 14:00
Discussion on a study linking football play duration to cognitive deficits.
“The more specialties, the more diseases.”
Impact of Football on Neurocognitive Health
14:00 to 17:08
Explore the findings on neurocognitive deficits among football players and discuss potential solutions.
“I did not find this study very surprising.”
Understanding GLP-1s and Their Effects
20:08 to 27:26
Dive into the science of GLP-1s, their development, and implications for weight loss and other health issues.
“So I want to set the stage here a little bit because I think that there is a kind of GLP-1 1.0 conversation that people can hear.”
Broader Implications of GLP-1s
27:26 to 28:01
Investigate the potential benefits of GLP-1 medications beyond weight loss, including their effects on kidney and cardiovascular health.
“A next interesting question is what about the other benefits?”
Impact of GLP-1s on Cancer and Metabolic Diseases
28:01 to 29:59
Learn about how GLP-1 medications may reduce obesity-related cancers and other metabolic diseases.
“think about the non-diabetes effects based on whether they are related to a reduction in weight or are they something else entirely.”
Behavioral Changes Induced by GLP-1s
30:00 to 31:58
Explore how GLP-1s may influence behaviors like alcohol and smoking consumption.
“But what always kind of gets me interested, and I want to ask you this, Emily, are the things that really can't plausibly be related to weight loss.”
Questioning Weight Loss Mechanisms with GLP-1s
31:59 to 34:00
Delve into whether weight loss through GLP-1s differs from traditional methods.
“There's something about the way this is interacting with people's brain chemistry that could be consistent with some of these effects.”
Muscle Loss During Weight Loss
34:01 to 36:39
Understand the connection between weight loss and muscle loss, regardless of method.
“And because it's not the real way to lose weight, it does these certain bad things.”
Show all 26 chapters
Combining GLP-1s with Strength Training
36:40 to 38:48
Discover the importance of strength training and protein intake while using GLP-1s.
“So Emily, let's say I don't want to lose muscle, or at least I don't want to lose as much muscle as possible.”
Weight Regain and Long-term Use of GLP-1s
38:49 to 41:20
Examine the concerns regarding weight regain after stopping GLP-1 medications.
“I think we should get into the things that people raise about that are more concerning.”
Microdosing GLP-1s for Maintenance
41:21 to 42:00
Learn about the concept of microdosing GLP-1s for weight maintenance post-treatment.
“Some go out to like a year and three months or so, but that's the extent of the data.”
Microdosing and Maintenance Doses of GLP-1s
42:00 to 44:25
Learn about the concept of microdosing GLP-1 medications and their practical applications.
“Like, yeah, you'll be on it, but you're only going to be on a little bit?”
Side Effects of GLP-1 Medications
44:25 to 46:41
Understand the common and serious side effects associated with GLP-1 drugs.
“the all-protein diet for six months and then gained it back, which is in fact how people interact with diets.”
Impact on Mental Health and Behavior
46:41 to 49:11
Explore how GLP-1 medications might influence mental health and behavior, including depression and addiction.
“Like you don't get the like high of eating food or the high of drinking alcohol.”
Sexual Effects and Relationship Dynamics
49:11 to 52:27
Discuss the sexual side effects of GLP-1s and how they can impact relationships.
“As I was looking in, I'll just say there are like 10 times as many studies on male impotence and anorgasmia from GLP-1s than there is on female.”
Ozempic Face and Weight Loss Perception
52:27 to 55:39
Delve into the concept of 'Ozempic face' and societal perceptions of weight loss.
“But if you think of like Al Roker, before and after he had gastric bypass, before and after that, he looked very different.”
Economic Impacts of GLP-1 Medications
55:39 to 56:00
Examine the broader economic implications of GLP-1 medications on healthcare and industries.
“Yeah, I mean, those are much slower moving changes.”
Economic Implications of GLP-1s
56:00 to 57:20
Explores how GLP-1 medications can offset healthcare costs through reduced disease.
“like a government payer, is that they will lower people's risk of other things.”
Long-term Effects of GLP-1 Usage
57:20 to 59:10
Discusses concerns about the long-term safety of GLP-1 medications and their impact on health.
“That sure, they seem to be working great now, but how do we know that if you're not on it for 30 years, it causes cancer or something like that?”
Off-label Use and Body Image Issues
59:10 to 1:01:00
Addresses the off-label use of GLP-1s and the societal implications on body image.
“And we lost a little bit of what I thought was probably a good move towards the idea that people could be different sizes and not just a size two.”
Future Directions for GLP-1 Medications
1:01:00 to 1:02:40
Speculates on future innovations and approvals of GLP-1 medications, especially for children.
“So Perry, before we get to our final feelings on this, let's talk about sort of where this is going and both in terms of the medications and in terms of kids.”
Debate on GLP-1 for Kids
1:02:40 to 1:04:40
Explores the implications of using GLP-1 medications in children and the need for careful consideration.
“In fact, as you lose weight, a lot of those cells are just shrinking, not necessarily dying off or evaporating.”
Smash or Pass?
1:04:40 to 1:04:50
The hosts summarize their feelings on GLP-1 medications with a fun segment title.
“After the break, we'll get to your question.”
Wrap-Up and Upcoming Topics
1:10:01 to 1:10:20
The hosts conclude today's discussion and preview the next episode's topic.
“And so the only way to purchase this online right now is in a nine pound tub.”
Transcript
Automatic transcript. May contain errors.0:00Emily Oster:Peace to the planet. Charlamagne Tha God here. And listen, we are back. The Black Effect Podcast Festival is back in Atlanta on April 25th at Pullman Yard. And the full lineup is nuts. We got the Grit Sineggs podcast, Deontay Kyle and Big Ice Cup Cat. We got Club 520 with Jeff Teague and the gang. Don't call me white girl. Mona will be there. Keep it positive, sweetie, with Crystal Renee. We got reality with the king with Carlos King. And yes, Drink Champs will be in the building. Plus, you know, we're going to have a lot of guests. So you need to join us. And we got the Black Effect Marketplace, the picture podcast, and everything you expect from the Black Effect Podcast Festival.
0:38Emily Oster:Tickets are on sale right now. Go get yours at blackeffect.com slash podcast festival. Don't play yourself, okay? Pull up.
0:50Emily Oster:What if mind control is real? If you could control the behavior of anybody around you, what kind of life would you have? Can you hypnotically persuade someone to buy a car? When you look at your car, you're going to become overwhelmed with such good feelings. Can you hypnotize someone into sleeping with you? I gave her some suggestions to be sexually aroused. Can you get someone to join your cult? NLP was used on me to access my subconscious. Mind Games, a new podcast exploring NLP, a.k.a. neurolinguistic programming. Is it a self-help miracle, a shady hypnosis scam, or both? Listen to Mind Games on the iHeartRadio app, Apple Podcasts, or wherever you get your podcasts.
1:29Emily Oster:Then she says, have you seen a photo of my son? And I'm like, who is this person?
1:35Perry Wilson:Welcome to the Boys and Girls podcast. Arranged marriage is basically a reality show, and you're auditioning for your soulmate. And who's judging? Only your entire family? I sacrificed myself to this ancient tradition, hoping to find love the right way. And instead, I found chaos, comedy, and a lot of cringe. Listen to Boys and Girls on the iHeartRadio app, Apple Podcasts, or wherever you get your podcasts. This Women's History Month, the podcast Keep It Positive, Sweetie celebrates the power of women choosing healing, purpose, and faith, even when life gets messy.
2:09Emily Oster:Love is not a destination. You have to work on it every day. Keep It Positive, sweetie, creates space for honest conversations on self-worth, love, growth, and navigating life with grace and grit, led by women who uplift, inspire, and tell the truth out loud. I have several conversations with God, and I know why it took 20 years.
2:29Perry Wilson:To hear this and more, listen to Keep It Positive, sweetie, on the iHeartRadio app, Apple Podcasts, or wherever you get your podcasts. Hey, Perry. How you doing? I'm good.
2:41Emily Oster:Emily, nice to see you.
2:42Perry Wilson:Nice to see you. Okay, today we are talking about GLP-1s. I'm going to ask you some questions. Do you know anyone using a GLP-1?
2:50Emily Oster:Well, wait, I've never heard of this. What is a GLP-1? No, I'm just kidding. I'm kidding. Yes, of course I know people on GLP-1s.
2:58Perry Wilson:Do you know people using them off-label?
3:00Emily Oster:Yes.
3:00Perry Wilson:Do you know people who are using other people's GLP-1s from their refrigerator? Yes. Do you know people who are microdosing GLP-1s? Yes. Yes. Do you know any wait? Do you know anyone who is micro dosing GLP one so they can focus better at their tech job?
3:18Emily Oster:OK, you got me there. I will. I will take a drink.
3:21Perry Wilson:I'm a yes on that one.
3:23Emily Oster:Wow. I want to hear more, but it might have to happen offline.
3:30Perry Wilson:I'm Emily Oster. I'm an economist and a data expert. And I'm Perry Wilson. I'm a medical doctor. It's Thursday, March 5th, 2026. And this is Wellness Actually.
3:40Emily Oster:Because you're getting a staggering amount of health and wellness information nowadays from every source imaginable. And some of it is awesome.
3:48Perry Wilson:And some of it is, well, actually bullshit. Fortunately, we're both people who know how to read studies, how to parse the data, and can tell you what's worth thinking about and what you can safely ignore.
4:02Emily Oster:But before we dig in, a note that this podcast is for educational purposes and should not be construed as medical advice. We don't know your unique situation, so talk to your doctor for personal health decisions.
4:12Perry Wilson:This week, we're asking, what's the deal with GLP-1s? And you will get our highly official thumbs up or thumbs down verdict. And then we'll get to your question of the week. But first, let's do the health news roundup after the break.
4:35Emily Oster:This episode is brought to you by Spreaker, the platform responsible for a rapidly spreading condition known as podcast brain. Symptoms include buying microphones you don't need, explaining RSS feeds to confused relatives, and saying things like, sorry, I can't talk right now, I'm editing audio. If this sounds familiar, you're probably already a podcaster. The good news is Spreaker makes the whole process simple. You record your show, upload it once, and Spreaker distributes it everywhere people listen. Apple Podcasts, Spotify, and about a dozen apps your cousin swears are the next big thing. Even better, Spreaker helps you monetize your show with ads, meaning your podcast might someday pay for, well, more microphones.
5:16Emily Oster:Start your show today at Spreaker.com. Spreaker, because if you're going to talk to yourself for an hour, you might as well publish it.
5:24Perry Wilson:What if mind control is real? If you could control the behavior of anybody around you, what kind of life would you have?
5:30Emily Oster:Can you hypnotically persuade someone to buy a car? When you look at your car, you're going to become overwhelmed with such good feelings.
5:38Perry Wilson:Can you hypnotize someone into sleeping with you?
5:41Emily Oster:I gave her some suggestions to be sexually aroused.
5:44Perry Wilson:Can you get someone to join your cult? NLP was used on me to access my subconscious. NLP, aka Neuro Linguistic Programming, is a blend of hypnosis, linguistics, and psychology.
5:56Emily Oster:Fans say it's like finally getting a user manual for your brain. It's about engineering consciousness. Mind Games is the story of NLP.
6:05Perry Wilson:It's crazy cast of disciples and the fake doctor who invented it at a New Age commune and sold it to guys in suits. He stood trial for murder and got acquitted. The biggest mind game of all? NLP might actually work.
6:20Emily Oster:This is wild. Listen to Mind Games on the iHeartRadio app, Apple Podcasts, or wherever you get your podcasts.
6:28Perry Wilson:The more you listen to your kids, the closer you'll be.
6:31Emily Oster:So we asked kids, what do you want your parents to hear?
6:35Perry Wilson:I feel sometimes that I'm not listened to. I would just want you to listen to me more often and evaluate situations with me and lead me towards success. Listening is a form of love. Find resources to help you support your kids and their emotional well-being at SoundItOutTogether.org.
6:53Emily Oster:That's SoundItOutTogether.org. Brought to you by the Ad Council and Pivotal.
6:58Perry Wilson:Hi, everyone.
6:58Emily Oster:I'm Cheryl Strayed, author of Wild and Tiny Beautiful Things. I'm excited to share that I have a new podcast called Mind Over Mountain. In each episode, I interview athletes, adventurers, and adrenaline seekers to discuss the inner landscapes and life experiences that informed and inspired their extraordinary feats. I also bring a bit of advice into the mix so we too can better understand how to face our own seemingly insurmountable challenges. Do you know what I'm going to do? I'm going to pull out what you already have inside. We're coming into this world fighting for our lives. All I'm going to do is pull out what you already got inside.
7:35Emily Oster:We're there to support and celebrate each other. And that is not like a your story versus my story. You're going to walk up and over that dang mountain. You're not just going to put your mind over it. Yep, yep, exactly. And if I can't walk up and over it, I'm going to go through it. Listen to Mind Over Mountain every Thursday on the iHeartRadio app, Apple Podcasts, or wherever you get your podcasts.
7:59Perry Wilson:All right, Perry. So Dr. Mike from the internet offered RFK Jr. $100 ,000 given to the charity of his choice to appear on his podcast. Would you take the$100 ,000? And what do you think about this?
8:16Emily Oster:Oh, my God, I would take$5 to appear on Dr. Mike's podcast. I've met Dr. Mike. I like Dr. Mike. He is actually one of these influencers who generally seems to have his head in the right place in terms of science-based medicine and things like that. And so I think RFK would be actually quite unwise to sit down with him and have a conversation. I think this is sort of a social media stunt a little bit. It gets some attention, but I'm here for it. I like people like this sort of fighting fire with fire in this space. So good on you, Dr. Mike. He's not going to take it.
Read the full transcript
8:55Perry Wilson:So I actually had a different reaction to this, which is twofold. One, I do like Dr. Mike very much. I would also be on his podcast for nothing. But one worry I have is that when you platform somebody, you platform them, they let them say the things that they think. And a lot of what RFK thinks doesn't make any sense. And also, what's the charity of choice? Is this going to mean Dr. Mike is donating to the anti-vax alliance? That would be some guardrails.
9:22Emily Oster:That's a great point. I mean, regarding platforming, he's the head of health and human services. He's got an adequate platform at this point. But you're right. Yes, he could definitely pick a particularly loathsome charity in this case. Let's stick in terms of health news with the government. Interesting confirmation hearing for Dr. Casey Means, who's been considered to be Surgeon General. At the time of this recording, there has not been an official vote on whether she would be approved to become Surgeon General. Dr. Means is an interesting character firmly in the wellness space. Just for those of those who don't know who she is, she graduated medical school from Stanford and then went to an ear, nose and throat residency program, which she never completed.
10:12Emily Oster:So the way medicine works or doctoring works is you go to med school and then you do an internship and residency, which is sort of a supervised period where you're under the supervision of a senior doctor. And then you graduate that, you take your board exams and you become board certified. She dropped out about six months prior to graduation from the ENT program, which is particularly odd. According to her book, she did it because she became disillusioned with modern medicine and the sort of, you know, culture of treating disease and not preventing it. because of that narrative, she's sort of become a darling of the alternative medicine space, you know, someone who is deeply entrenched in like the evil world of medicine and escaped.
10:56Emily Oster:There's an interesting article in Vanity Fair, which interviews some of her co-residents and a former chair of ENT who actually say she dropped out because of stress. So there's a little bit of retconning potentially going on here. I want to get your impression on her, but I need to know how you'll respond to this little bit of audio I found. This is not from her confirmation hearing. This is from a podcast, but I'm going to play you some Casey Means audio to get your reaction.
11:21Perry Wilson:The more specialties we invent in healthcare, the sicker we're getting. The more drugs we
11:29Emily Oster:prescribe in the United States for these different chronic illnesses, the increase in the rates of these diseases. So the more drugs for the diseases, the higher amounts of these diseases we get. The more specialties, the more diseases. Literally, the more research that we publish on these diseases, the worse the diseases are getting. Well, all right, Perry.
11:53Perry Wilson:So first of all, I think she's confused about reverse causality. That's probably a little more technical than you were hoping to get, but it is true. That is exactly what I was hoping to get. We do more work on a disease when it is worse. But I think to conclude that it is the research that we do on the disease that makes it worse is perhaps the wrong direction as opposed to when there's more of a disease, we do more research on it. So I don't think the causality goes the direction that she thinks.
12:21Emily Oster:It's one of the stupidest takes I've ever heard from someone with an MD after their name.
12:26Perry Wilson:It's a stupid take. It's on the stupider side. I agree. However, I will say that I feel like there's been a lot of credentialing of Dr. Means and saying she didn't finish her residency and blah, blah, blah. I am much more concerned about the things she's saying than whether she completed this particular component of her training. And if she were saying very sensible things which made sense and were consistent with science, the fact that she left her residency with six months left, that's sort of of that's kind of her business. My much bigger concern is that a lot of what she's saying does not comport with the science, that I think the idea of having someone who is America's top doctor, which is one of the ways you think can think of the Surgeon General, to have that person be unwilling to say that vaccines are a good idea and to be unwilling to say, as she was in the confirmation, to be unwilling to say that the flu vaccine reduces flu mortality.
13:24Perry Wilson:I mean, that just feels like, really? Can we do that?
13:28Emily Oster:Yeah. And the sort of refrain that she had, which was obviously prepared, was like, oh, well, you should talk to your doctor about this. This should all be a discussion between a patient and a doctor. I'm not saying it doesn't work, but you should discuss with your doctor. It's not my place. And it's like, no, no, no. Actually, when you're the Surgeon General - It is your place. That's your place. It's totally your place. It's your place.
13:51Perry Wilson:This is what you're here for. Okay. Well, we'll see what happens there. All right. Last thing we want to talk about was a new study of football players, which is showing multiple neurocognitive deficits in general in this large sample of football players with dose response effects based on years of play, which is just a fancy way of saying the more years people play, the more neurocognitive deficits we are seeing. I did not find this study very surprising. We have a lot of evidence that repeated concussions, which is probably a lot of what's going on here, or even the moderate forms of head trauma that do not elevate to the point of a concussion, that those can have long-term effects.
14:38Perry Wilson:But I'm curious if you had a different take on this.
14:43Emily Oster:No, this is a nice study, 4 ,000 football players, you know, from high school players on up. So this wasn't just restricted to NFL players. And as you say, consistent with a lot of prior data. And I love football. Like I love watching football. I have been an Eagles fan for a long time. I mean, I didn't love it this year particularly, but in general. But it is hard for me to kind of see this data come out over and over and over again. And it's clear that something is happening here. And it's like, we're all doing that. What's that meme of like, I don't know, it's like a rodent or something who just kind of like looks like looks to the side, like, am I going to say anything?
15:26Emily Oster:I don't know. You guys know what that meme is? I don't know. It's, it's like, are we gonna address this? Or are we just going to kind of be like, okay, this is how football works? Because it seems like this is how football works.
15:37Perry Wilson:It is how football works. I mean, I think if you're looking for a sort of middle of the road solution from a smart person. I don't, do you remember Chris Nowinski, who we went to college with? Yeah. Yeah. So Chris runs an organization that studies concussions in football and tries to ameliorate this problem by, for example, not encouraging people to not have tackle football before the age of 14. So to say, hey, if there's a dose response, let's like limit the amount of time kids are actually having contact in football and then sort of maybe make some changes to how college football is practiced so there's less head injury.
16:19Perry Wilson:So Chris is doing really, really interesting work. We can put a link in the show notes to his organization.
16:25Emily Oster:I love it. That's awesome. My son did flag football for the past couple seasons. He's 13. It's super fun.
16:32Perry Wilson:My kids hate sports, so that's not a concern for me, but I know that it is for some.
16:37Emily Oster:When we come back, we will ask, what's the deal with GLP-1s?
17:08Emily Oster:once, and Spreaker distributes it everywhere people listen. Apple Podcasts, Spotify, and about a dozen apps your cousin swears are the next big thing. Even better, Spreaker helps you monetize your show with ads, meaning your podcast might someday pay for, well, more microphones. Start your show today at Spreaker.com. Spreaker. Because if you're going to talk to yourself for an hour, you might as well publish it.
17:32Perry Wilson:What if mind control is real?
17:35Emily Oster:If you could control the behavior of anybody around you, what kind of life would you have? Can you hypnotically persuade someone to buy a car? When you look at your car, you're going to become overwhelmed with such good feelings.
17:46Perry Wilson:Can you hypnotize someone into sleeping with you?
17:49Emily Oster:I gave her some suggestions to be sexually aroused.
17:52Perry Wilson:Can you get someone to join your cult? NLP was used on me to access my subconscious.
17:58Emily Oster:NLP, aka Neuro Linguistic Programming, is a blend of hypnosis, linguistics, and psychology. Fans say it's like finally getting a user manual for your brain. It's about engineering consciousness. Mind Games is the story of NLP. It's crazy cast of disciples
18:15Perry Wilson:and the fake doctor who invented it at a new age commune and sold it to guys in suits. He stood trial for murder and got acquitted. The biggest mind game of all? NLP might actually work.
18:28Emily Oster:This is wild. Listen to Mind Games on the iHeartRadio app, Apple Podcasts, or wherever you get your podcasts.
18:37Perry Wilson:Babes, what are you doing? What? I'm just mowing the lawn. No, it's blazing hot and dry out here. Don't you remember? Smokey Bear says...
18:46Emily Oster:Avoid using power equipment when it's windy or dry. Where'd you learn this?
18:50Perry Wilson:Oh, it's on...
18:51Emily Oster:SmokeyBear.com, with many other wildfire prevention tips. Right. Thanks, honey bear. Because remember, only you can prevent wildfires. Brought to you by the USDA Forest Service, your state forester, and the Ad Council. Hi, everyone. I'm Cheryl Strayed, author of Wild and Tiny Beautiful Things. I'm excited to share that I have a new podcast called Mind Over Mountain. In each episode, I interview athletes, adventurers, and adrenaline seekers to discuss the inner landscapes and life experiences that informed and inspired their extraordinary feats. I also bring a bit of advice into the mix so we, too can better understand how to face our own seemingly insurmountable challenges.
19:35Emily Oster:Do you know what I'm going to do? I'm going to pull out what you already have inside. We're coming into this world fighting for our lives. All I'm going to do is pull out what you already got inside. We're there to support and celebrate each other. And that is not like a your story versus my story. You're going to walk up and over that dang mountain. You're not just going to put your mind over it. Yep, yep, exactly. And if I can't walk up and over it, I'm going to go through it. Listen to Mind Over Mountain every Thursday on the iHeartRadio app, Apple Podcasts, or wherever you get your podcasts.
20:08Perry Wilson:All right, Perry, GLP-1s. So I want to set the stage here a little bit because I think that there is a kind of GLP-1 1.0 conversation that people can hear. Like, what are these? Do they work for weight loss? And we will touch on that. But I think at this point, this is so ubiquitous that people probably don't want to hear like GLP-1s are effective for weight loss. I actually want to focus most of our conversation, if you're up for it, on thinking about the sort of 2.0 questions. So if people have lost weight, what about weight regain? What are the other things this might work for? What are the big concerns people have?
20:43Perry Wilson:What about the long-term effects? There are some interesting economic questions, which I'm dying to discuss.
20:49Emily Oster:I love it. This is not freshman year anymore. Welcome to Senior Seminar.
20:53Perry Wilson:Exactly. Senior Seminar GLP1s. Okay. But before we get to, or maybe as part of Senior Seminar, can we talk about the Gila Monster? Is it Gila Monster or Gila Monster is my first question. And can you tell me why it's such an important animal?
21:07Emily Oster:I say Gila Monster. I don't know if that is correct. You can write to us at wellnessactually.fm and correct everything we say. It is important. This is so interesting. So GLP-1 is a substance produced by your body and has been known since the 70s. And even its effects were known in the early 80s. So they took people and they gave them infusions of human GLP-1. And what they found is that their gastric emptying really slowed down and they reported more satiety. So they like weren't as hungry. But there was this problem. And that's that GLP-1 that your body makes has a half-life of about a minute.
21:46Emily Oster:And so as long as it's directly infusing into your vein, you don't feel hungry. But once you disconnect the IV, you do. So not a viable product for weight loss, obviously. And that was the state of things for 10 years or so. And then we get to a weird lab at the NIH. A guy named Jean-Pierre Routhman was working in John Pisano's NIH lab testing venoms of various venomous animals. This is one of those examples of like basic science. Like they had no idea what they were looking for. It was just like venom's interesting. We should know more about venom. And great. This guy, Routhman's job was to extract venom from the Gila monster.
22:29Emily Oster:and he noticed that when he injected this venom into mice, it did weird things with their blood sugar and their pancreas. He wasn't sure what it was. In 1992, a scientist named John Ang isolated the protein in Gila monster venom that was causing all these blood sugar issues. It was called Exendin-4, and that was developed into a drug called Exenatide or Bayetta, the first GLP-1 drug, which was FDA approved. Do you want to guess when? 2005. This is not new science. But what was amazing about the Gila monster venom is that protein in the venom or that peptide in the venom looked like human GLP-1 bound to the same receptor as human GLP-1, but it didn't break down in the blood in a minute.
23:14Emily Oster:It broke down over the course of about a day. And so you could get away with injecting it or the cleaned up variants that was eventually produced called exenatide. once a day, and all of a sudden this was a viable product.
23:28Perry Wilson:So I just want to be clear, this is a peptide. So for people who listened to the earlier episode on peptides, this is an example of a peptide that is approved, not like the Wolverine stack. So go back to that episode for context there. Yeah. So, okay. I think one interesting follow-up question before we get to some of these details is actually a question of why now we're discussing this. So if 20 years ago, we developed this venom, why is it now that we are seeing so much more of this, which feels like it's kind of come up in the last three years? So what is, is there another science breakthrough that is more recent?
24:07Emily Oster:Not really. It's been just kind of a gradual, as these things kind of go, like once the class is discovered, it's like, okay, this class of chemicals is discovered, there's iterative improvements over time. And basically the improvements have been two things. Number one, increased potency, which means that they've developed peptides that bind a little more tightly to the GLP-1 receptor in our cells, and two, increased half-life. So where semaglutide, which also some people say semaglutide, but I say semaglutide, or ozempic came along with a once-weekly dose because it was stable in your blood for a much longer period of time, had a much longer half-life.
24:41Emily Oster:That's where you start to get people willing to think about this for treatment of obesity. Most people without diabetes aren't comfortable injecting themselves once a day with a product. And in fact, even people with diabetes, no one loves injecting themselves, right? And so once a week was a thing. There was another milestone in the obesity literature, which was this magical 10 % weight loss threshold, which had always been the arbitrary marker of, is this drug successful for weight loss? And Bayetta, the first GLP-1, was not. It led to some weight loss, about 2 % to 3 % over the course of the year, but just wasn't potent enough and still is used for diabetes control, blood sugar control.
25:24Emily Oster:You got the first greater than 10 % weight loss effect with loraglutide, which came out later. And that sort of set off the arms race that we have now where you're just inventing drug after drug that are more potent and more potent. And of course, like the most recent trial, Lilly's new drug, which I can't even say.
25:42Perry Wilson:Don't even try.
25:43Emily Oster:So retratratratide had a 28 % year-on-year weight loss, which is insane.
25:51Perry Wilson:Okay. So right now we find ourselves in a moment where the two medications that people are most commonly using for weight loss are Wagovi and Zepbound. Wagovi is semaglutide. It's the ozempic equivalent, but prescribed for weight loss. Zepbound is trisepatide. It's the Manjaro equivalent, but prescribed for weight loss. Both of these lead to something between 15 % to 20 % weight loss in the first year. In the trial data, they are both served through a weekly injection that people give themselves. And the next thing that's coming is a set of, we're going to keep seeing innovation here. The next thing that's coming is an oral form from Eli Lilly, which has a slightly lower amount of weight loss.
26:36Perry Wilson:But my guess is that the uptake will be very high because people would rather take a pill than have an injection. So we really find ourselves in a moment, this is kind of the Ozempic 1.0, where these medications are incredibly effective for weight loss. They're much more effective than pretty much anything we have had in terms of diet and exercise. They just work really well. And more and more things that are developed are going to make them work better. to the point, I think, you know, you discussed the latest trial with 30 % weight loss. Like people are starting to have a conversation about like, what's too much?
27:09Perry Wilson:Like how much weight loss is, is too much weight loss? Like 30 % is a lot in a year. And so we're kind of at the point where probably it's almost enough, although people always like more, but I think it's very clear that these are effective for weight loss. And that is like, the science is done on that particular piece. A next interesting question is what about the other benefits? So before we get into like the things we're concerned about, these were originally prescribed for diabetes. They are effective for weight loss, but we're starting to see all kinds of claims like this is good for kidney disease.
27:43Perry Wilson:It's good for cardiovascular disease. This is good for, you know, I don't know, like cancer, cancer for everything. I mean, which of these things are best supported? I'm going to ask you because I think one of the best supported one is the kidneys and you are, in fact, a kidney doctor.
27:57Emily Oster:Yeah, all these kind of off-target effects. And I think it's good to think about the non-diabetes effects based on whether they are related to a reduction in weight or are they something else entirely. So let's take cancer as an example. So there have been several studies that have shown that the use of these drugs reduces the rate of obesity-related cancers. So the classic obesity-related cancers, cancers that are driven by some of the hormones that come from fat and stuff like that, like breast cancer, cancers of the GI tract, colon cancer, and the rates of those things do go down. But it's plausible, we always talk about biological plausibility, that the reason they're going down is not because these drugs magically kill tumor cells, it's because people lose weight and weight is a risk factor for the development of these types of cancers.
28:46Emily Oster:That's a similar mechanism for like a reduction in blood pressure, for example. If you lose weight in any way, your blood pressure goes down. Same thing for kidney disease, broadly speaking. The more weight you have, the more metabolically active tissue you have in your body, the more work the kidney has to do. And in general, if you can give the kidney less work to do, it's happy to not have to do as much and they can kind of last longer. I think it's probably similar for cardiovascular disease as well.
29:10Perry Wilson:So I will say that I think that in some of these trials, when they're looking at other kinds of cardiovascular disease and so on, there's sort of some discussion that maybe the effects are larger than you would expect based on weight loss alone. So they're sort of trying to do a kind of calibration and then say, well, maybe it's like a lot of the weight loss, but then there's something that you get more. Although I think that's obviously a very hard thing to sort of separate fully in the data.
29:38Emily Oster:Yeah. And it relies on some assumptions of like, you know, how many pounds of weight is equivalent to how many millimeters of mercury of blood pressure that are always like a little bit hand wavy. So that's all true. Like the epidemic of obesity in our country and around the world is driving much of the chronic disease epidemic. It just is. And so anything that impacts obesity, whatever it is, is going to reduce the rates of those diseases. That's cool. But what always kind of gets me interested, and I want to ask you this, Emily, are the things that really can't plausibly be related to weight loss.
30:11Emily Oster:So what do you think about like the fact that people report less smoking or alcohol intake or gambling like this stuff?
30:19Perry Wilson:Yeah. I mean, I think, so my senses of those things, the one that is most strongly supported in the data is alcohol, partly because that's where we've studied the most and partly because that's an activity that most people engage in. There's a lot of reports in both the data and just out in the world that people's interest in alcohol declines as a result of this and that other, you know, their interest in smoking, they're interested in all these other kind of maybe what we consider vices goes down. One interpretation of the way these medications work is that there's something about sort of almost like sort of self-control, like inhibition value.
30:57Perry Wilson:And I mean, this is consistent with when you talk to people who take these medications, and I have not, but I've talked to a lot of people. One of the things that is very common for people to say is like, it turned off the noise. like my head was full of food noise and I was always thinking about food and I was always thinking about that and this made me think about it less. And if you think about the way that a lot of people feel about alcohol or smoking or whatever, it is also that noise. It's like, I feel the noise, I wanna have a drink or I feel the noise, I wanna have a cigarette. You can imagine that whatever is that mechanism, it might work there.
31:28Perry Wilson:Similarly, I know people who take this for focus, who microdose like a ZepBound for focus.
31:34Emily Oster:Yeah, talk to me about that. I've never heard that before.
31:36Perry Wilson:I don't know. These guys in Silicon Valley do a lot of weird stuff, Perry. And one of the things that people's is like, it really helps you focus. It helps you not be distracted by whatever food noise, alcohol noise, smoking noise, other kinds of noise. Certainly, I would not say that we have science or data or evidence that supports that piece. But putting all of these things together, it does feel like maybe there's something in there. There's something about the way this is interacting with people's brain chemistry that could be consistent with some of these effects. Actually, there's someone, I believe there are some people thinking about experimenting on providing people GLP-1s when they leave prison.
32:16Perry Wilson:And one of the outcomes they would look at is recidivism. And one interpretation of that is that basically if you could turn down people's impulses to engage in alcohol and drugs and so on, they might actually be less likely to return to prison.
32:30Emily Oster:Wow.
32:30Perry Wilson:So.
32:31Emily Oster:Dude, fascinating. Totally fascinating. That's interesting.
32:34Perry Wilson:Again, this is like, we're on the line. Yeah, of course, we're way out there. You know, we're way out there. We're way out.
32:38Emily Oster:There is plausibility here, though. I mean, one thing that people know, I think 1.0 people know that GLP-1's decreased gastric emptying. So that just feeling of having a full stomach, it really does seem like that is not everything here. I did a quick review of like where GLP-1 receptor is found in your body. So, you know, what kind of cells express these receptors in high levels. And yes, they are throughout the GI tract and pancreas and things like that. But right up there in terms of organ systems is the brain. So your brain has these receptors. We do know that these peptides can cross the blood brain barrier.
33:13Emily Oster:And once a drug can cross the blood brain barrier, and once you know there's receptors on your neurons for that drug, like it kind of opens the door of anything being possible to some extent, right? So all of these things are definitely plausible.
33:26Perry Wilson:So if one thing people wonder about sometimes is when you're on these and you lose weight, is it quote the same as losing weight in other ways? Is it literally just this makes you eat less and you eat less and then you lose weight, like can measure it with the way you would lose weight if you just literally ate less? Is there something more than that or is that kind of the whole business?
33:46Emily Oster:Oh, this is such a good question because so much of what I see online, there is like an anti-GLP1 current that is under there. And typically the arguments do go something like this. This is not natural. This isn't the real way to lose weight. And because it's not the real way to lose weight, it does these certain bad things. And I think the one that you hear about the most is probably muscle loss. And people come and are like, oh no, you're not just losing fat, you're losing muscle. And Emily, I know you've looked into this. So I will ask you, is it true that if I lose weight through other means like diet and exercise that I only lose fat and don't lose muscle.
34:27Perry Wilson:That is not true, Perry. When you lose weight in any way, you lose both fat and muscle. And some of that is like sort of intimately linked because one of the things your muscles do, actually the main thing for most of us, our muscles are doing are moving us around in the world. And so if you are heavier, your muscles are moving more stuff. It's like you're constantly wearing a weighted vest. And when you lose weight, even if you just lost fat, Your muscles would be like, great, we don't have to have so much of us anymore because we aren't moving around so much weight. And so there is like an inherent feature of losing weight where you are going to lose some fat and some muscle.
35:06Perry Wilson:And if you have a lot of fat, you will lose relatively more fat. But no matter how you lose weight, you are losing some muscle. And that is also true on Ozempic. And actually, the study suggests it's no more true on GLP-1s than it is with other kinds of diet. Like you just lose some fat and some muscle.
35:20Emily Oster:Yeah, and typically about 30 to up to 50 % of weight loss can come from muscle regardless of what the weight loss is. There is a little wrinkle here that I don't see brought up often, but I'll say it because we're in senior seminar. And that is that the way that muscle mass gets assessed typically in these studies is through a DEXA scan, which is sort of a – think of it like an X-ray, but you can see muscle tissue. You do a whole episode.
35:47Perry Wilson:Influencers love a DEXA scan.
35:49Emily Oster:Oh, interesting. Okay. So DEXA scans don't actually distinguish between muscle and what's called lean mass, just like nonfat, nonbone mass. So they sort of assume that like everything that isn't bone and isn't fat is muscle, which is obviously not true. You have like organs and stuff like that. But it's more than that, which is that fat infiltrates muscle. And DEXA scans cannot determine how much of your muscle is infiltrated by fat. It just looks like more muscle. You can think of this as like the marbling of a steak, right? Like if you fatten these cows, you get nice prime rib and things like that.
36:26Emily Oster:And it really tastes delicious, but it's actually bad for your muscle quality. And so it may be that some of the fat loss is happening within muscle, which is almost certainly a good thing. But yes, you're going to lose muscle if you lose weight, no matter how you lose weight. So Emily, let's say I don't want to lose muscle, or at least I don't want to lose as much muscle as possible. Can I prevent this or am I doomed? Yeah.
36:49Perry Wilson:So one of the totally fascinating, like knock on impacts of the Ozempa craze is the strength training craze. So the idea that you sort of like all of a sudden you're on the GLP one for weight loss, but now you need to do strength training. And that's actually not crazy. we think about like, how do you retain and build muscle? You retain and build muscle by exercising and in particular by exercising in a way that, you know, cardio, yes, but also like by lifting stuff. And so there's a kind of combo here where you take the GLP-1 for weight loss and you exercise for muscle retention, which tends to be a good combo.
37:29Perry Wilson:And interestingly, many people report their willingness to exercise and like get up and go to the gym is greater when And they're on a GLP-1 getting back to potentially some of the stuff that we talked about before around sort of impulse control. The other thing is prioritizing protein, right? So like so much of what's happening when people are on GLP-1s is they eat less food, like fewer calories, but making sure that those fewer calories are actually like you're maintaining protein. The amount of protein shouldn't change that much, whereas the amount of other things should change more and kind of thinking about that balance.
38:01Perry Wilson:So there's still like a need to think about diet and exercise, even if the GLP-1 is acting. I will say I was at an influencer dinner at some point a few months ago and get into the economy later. But I think restaurants have really adapted to this because all they serve was protein. Like it was just exclusively protein. There was like one tiny thing of French fries on the table. And like, I like carbs.
38:25Emily Oster:Yes, you're a carb queen.
38:27Perry Wilson:I was sad. I was sad about it. It's like, where's the bread service? But the bread service is over at fancy restaurants.
38:35Emily Oster:Yeah, yeah. It's just egg white service now and protein water.
38:38Perry Wilson:Tuna and egg whites exclusively. Okay, so that is the kind of, I think, big picture of like sort of what happens initially when people are on this and what are some of the other things it could work for. I think we should get into the things that people raise about that are more concerning. The first of which is weight regain. the question of, do I need to be on this forever? And I will say in the trials, the evidence is pretty sharp that when you put someone on a GLP-1, they lose 20 % of their body weight, you take them off their GLP-1, they gain back about half of their body weight, at least in the trials.
39:17Perry Wilson:So is this a life sentence? And is that a problem, I guess, is my secondary question.
39:24Emily Oster:I think the data is quite clear. But like, you know, part of me as a doctor is like, well, we have lots of medications like this. Like when I treat someone for hypertension, and I put them on a blood pressure pill, in general, the expectation is like, yeah, if you stop this blood pressure pill, you will your blood pressure will go up again. Like that's your there is some constitutive effect there. One of the things I've seen online from influencers, though, who are kind of anti-GLP1s is like, oh, but if you lose weight through lifestyle change and changing your habits, then you'll have that forever.
39:59Emily Oster:But with GLP1, you're stuck for life. And you know this data as well as I do, Emily.
40:03Perry Wilson:It's the stupidest thing I've ever heard.
40:06Emily Oster:Like the data on maintaining weight loss with diet is abysmal. It's abysmal. It's abysmal.
40:16Perry Wilson:This is the, for me, like the stupidest piece of this discussion because it sort of presumes like, well, of course we had a way before for people to lose large amounts of weight and keep it off with diet. And now, you know, we're not using that anymore. It's like, actually, no, yes, it is possible to lose weight with diet. And some people do. And I know because they show up in comments when I talk about this and they're like, I lost 300 pounds doing yoga and walking around the block one time. And it's like, that's super for you. But for most people, that actually isn't effective. Most diets work for a little while and then people gain the weight back.
40:50Perry Wilson:It's very, very consistent. And so I'm not sure this is really any different than that, nor do I think it's very different, as you say, than something like a statin, which people go on and then they stay on forever, and which, by the way, you might be able to get off after you're on your GLP-1 because your cholesterol might improve. So that's another thing to think about.
41:09Emily Oster:Well, yeah, I was thinking the same thing with my blood pressure pill. I was like, actually, they might be able to come off if they start the GLP-1. The trials, one of the reasons we even have this data is because most of these trials last basically a year. Some go out to like a year and three months or so, but that's the extent of the data. And so we just don't know with that degree of fidelity, like what 10 years on a GLP-1 in terms of weight loss looks like. There's observational data to that effect because the GLP-1s have been around for so long. But the randomized trial data is limited in scope.
41:42Emily Oster:What is interesting is how people in the real world are kind of handling this. So yes, they lose a lot of weight. They get to a weight they're happy with. And then they're like, okay, I'm good. And what I've found with patients that I've spoken to is generally not like, okay, I'm going off GLP-1, but people are doing this thing that's called microdosing. So what do we know about microdosing? Is this the answer? Like, yeah, you'll be on it, but you're only going to be on a little bit?
42:08Perry Wilson:I don't think we have any idea. And I think the reason is sort of interesting in terms of the science. So think about the kind of who is running the trials of these. The people running the trials, the people who are making the drugs, right? Nova Nordisk, Gila Lily, the makers of the drugs run the trials. And they trial their drug at the dosage that they are going to sell it at, because that is what the FDA tells them to do. That's how drug trials work. They don't usually run trials of like, and here's exactly how you're going to do it in the real world. But in the real world, when people get to this, most of the doctors I know who are using this will do, I'm not sure they'd call it microdosing.
42:47Perry Wilson:They call it a maintenance dose, right? That we are like, we start with a low dose. We go up to a dose in which you're losing weight in a consistent way. You get to the weight that you would like to beat, and then you drop down the dosage until you get to a point where you are maintaining that weight and that feels comfortable. And that's how this is actually operating for most people in the real world. I'm not sure we're going to see trials of that in the short run because I'm not sure who would run them, right? So I don't think Novo Nordisk is going to run that kind of trial. Yeah. Somebody will eventually, but I think it's, and it's also just so like in ideal world, it's sort of so titrated.
43:22Perry Wilson:One of the concerns I think is that people are titrating it themselves, whereas a much better thing would be to titrate under the supervision of your doctor, not to just like take half your dose, which is my sense is what people are actually doing.
43:33Emily Oster:Right. And a lot of this has to be done actually through compounding pharmacies, which we've talked about in a prior episode, has potential safety concerns. The Ozempic pen has a little clicky dial that you can turn, which does allow you to change dose. My understanding is that the ZEP bound pen does not. So the only way to kind of microdose that is to break the thing open and like, don't do that. That's a bad idea. So you're kind of going outside the box a little bit here. But I agree. I think this is probably what happens. Like eventually we'll get to a point where, first of all, there will be oral drugs.
44:09Emily Oster:and this will be the kind of thing that you do probably take some lowish dose probably for an extended period of time unless you want to gain some more weight. Yeah.
44:19Perry Wilson:Okay. So it is a long-term medication, but maybe the right frame is this is a long-term medication, like your satin, your blood pressure medication and not a diet like the time that you tried to lose weight on the all-protein diet for six months and then gained it back, which is in fact how people interact with diets. Okay. The second big concern is just, are there side effects? Which there are. I think it should be very clear. Like this is a drug. It has side effects. The main side effect people complain about is nausea and other gastric problems. That is a, I think I've just a, that's a feature.
44:54Perry Wilson:I don't know if it's a feature or a bug. It's a very common side effect. What about some of these more serious things, pancreatitis, depression?
45:05Emily Oster:Okay, probably should go through very quickly, like one by one. Pancreatitis, yes. Rare case reports probably associated with these drugs. We know they act on the pancreas. In fact, that Gila monster venom, when a Gila monster bites a mouse, it causes an acute pancreatitis. So I buy it. Yes. Rarely, but yes. So people need to know like symptoms of that are a deep and painful burning in your upper part of your stomach. Like you'll know this is bad when it's happening. You definitely want to get checked out. Okay, the depression suicide thing. This is really interesting because we've talked already about the ability of these drugs to potentially modulate reward pathways in the brain.
45:48Emily Oster:And you framed it differently, Emily, for the first time. And it's like I'm still kind of grappling with the way you frame this. So the way I hear people frame this is like, oh, it takes away your desire to eat. It takes away your desire to smoke. It takes away your desire to drink alcohol. But like what it's doing is it's just it's kind of all the pleasure, pleasurable things that your brain wants. It just kind of cuts that off. And then like, are you joyless? Is there no is there no hope in the world? And if so, might it not increase depression and suicidality? RFK Jr. himself has raised this issue.
46:20Emily Oster:And I will just point out that the current best data is from a meta-analysis of 27 randomized controlled trials, including 32 ,000 people looking at the rates of suicide and self-harm from these drugs. And there is no difference in suicide or self-harm events between placebo and these drugs. So I do not think that is real. And one of the reasons, like the way you've reframed this for me is as opposed to saying like, oh, it cuts the reward pathways. Like you don't get the like high of eating food or the high of drinking alcohol. You've reframed it as like it's not ending that thing. It's giving you this like it's giving you control.
46:59Emily Oster:It's giving you more focus, which is I kind of like I mean, I don't know if it's true, but that is a different way to think about it. That might explain why you get less drinking, but not suicidality.
47:08Perry Wilson:I don't know. I mean, I think that is a way that I have heard people try to describe to me what this is like, which I think is a potentially interesting organization of some of these facts. But I don't know. Again, it's like, it's always hard to get inside of people's brains. It is.
47:24Emily Oster:When we talk about enjoyable things that your brain likes to do, something that always comes up is sex. So what do we know about sexual effects of these drugs?
47:35Perry Wilson:Relatively little. You know, there are people who will say like this limits your desire to have sex. I don't think there's a lot of evidentiary support for that. What I will say is there are some real issues that, you know, people in long-term relationships grapple with when they go on these medications, particularly if, you know, and the New York Times actually said a series of very interesting stories about couples where one person has gone on a JLP-1 and they sort of said, well, you know, our life used to revolve around going out to dinner and, and, you know, drinking together and hanging out and like, and now you, this person doesn't want to do those things anymore.
48:15Perry Wilson:And so, you know, maybe you, you do want to have sex, maybe you don't want to have sex, but there's another piece of, of, it's not about a lack of interest in a physical relationship, or maybe it is, but it's also about changing the relationship. And I actually think that's a really important part of this for a lot of people that eating is a huge part of our, of our lives. And if you change things, so you aren't going to eat in the same way, and you are in a relationship with another person, and they're not going to change that, and your body is going to be going through a lot of changes, like that is just an adaptation that people should expect and should, you know, think about as part of this.
48:55Perry Wilson:I think it's less about sex and more just about, you know, when you change something totally about yourself and your relationship, it changes and you have to adapt and relationships are hard is my fundamental feeling.
49:06Emily Oster:Yeah, indeed. I agree. There's sort of a disturbing lack of data on this. As I was looking in, I'll just say there are like 10 times as many studies on male impotence and anorgasmia from GLP-1s than there is on female. It's like, all right, researchers, get with the program here a little bit. Women are more likely to take GLP-1s and are more likely to lose a greater percentage of body weight on GLP-1s than men. Clearly, this needs to be looked into. I agree there's nothing terribly compelling. I did find one study that was an observational study looking at rates of a clinical diagnosis of anorgasmia, the inability to have an orgasm, which did find that compared to women not on GLP-1s, those on GLP-1s had that diagnosis code about twofold more often.
49:55Emily Oster:It's a very rare diagnosis code to get because most people don't talk about this with their doctor in the first place. But that rate was similar to women taking metformin, which is another drug for diabetes. So this is probably related to the underlying reason that the woman is taking the GLP-1 as opposed to the GLP-1 itself. But, you know, more data. I'd like more data here.
50:16Perry Wilson:Who doesn't want more data on women's sexual function as opposed to men's sexual function where really we're good? Thanks. It's enough data. We know everything. We got it. We're fine. Okay. I think there are some interesting social and like regulatory questions here, or maybe just social questions that we should make sure that we hit on. Last thing that I will say I'm bringing up in part because this is the first thing my father ever asked me about Ozempic. He was like, have you heard of Ozempic face? And then he was like, blah, blah, blah person that I know has it. And I'm like, yes, I have heard of that.
50:51Perry Wilson:So Perry, have you heard of Ozempic face?
50:54Emily Oster:Oh, I've heard of Ozempic face. I've heard of Ozempic butt. Yeah.
50:59Perry Wilson:So Ozempic face, my sense is that when you lose weight, your skin takes some time to tighten back up, which, or maybe it doesn't tighten back up and that you lose a lot of weight in your face or your butt, it will be saggy. It doesn't matter if it's on a GLP-1 or in some other way.
51:20Emily Oster:Yeah. We don't have that magic bullet that only makes you lose fat around your belly, but leaves shredded abs behind. When you lose weight, your body consumes fat. Fat is there to be a source of energy when you don't take in enough calories. That's what GLP-1s do. They make you eat less, so you expend more calories than you're consuming. Your body breaks down fat. as well as some other tissues, as we discussed, to recapture that energy. And it'll take fat from everywhere. What Ozempic face is, medically speaking, is midface volume loss. That's what the plastic surgeons call it. So that's sort of cheekbones and cheeks gives kind of a sunken appearance.
51:59Emily Oster:And you're right. This is what happens with all forms. Yep.
52:03Perry Wilson:But that one is social.
52:04Emily Oster:Emily, for those of you just listening on the podcast, is making kind of a fish face. This is what happens with all forms of weight loss. I think the reason it's in the zeitgeist now is that we just never had effective weight loss that was working for the masses. So where you will have seen this before is people getting gastric bypass surgery, which was like before the GLP-1s was the main way that people could lose a significant amount of body weight. But that's a big surgery. But if you think of like Al Roker, before and after he had gastric bypass, before and after that, he looked very different.
52:36Emily Oster:He had mid-face volume loss. We didn't call it a zempic face back then because it didn't exist. This is just weight loss phase. It is real. In fact, the American Academy of Facial Plastic and Reconstructive Surgeons reported a 50 % increase in facial fat grafting procedures in 2024. So people are thinking about it. Totally.
52:56Perry Wilson:Okay. I think that's a really good segue because I am very interested in the knock-on economic effects of these medications.
53:04Emily Oster:Oh, I love when you bring your economic doctorate into this discussion. What's going to happen?
53:08Perry Wilson:So I'm going to tell you.
53:10Emily Oster:And where do I invest?
53:11Perry Wilson:Okay. So if I were an investor, I will tell you, number one, I would invest in places that do excess skin removal. I'm not kidding. I think that there is going to be a huge excess demand for skin removal procedures, because if people have been overweight for a very long time and you lose, if you lose 300 pounds, you end up with a lot more skin and people can find it. They may not like how it looks, but also it can be uncomfortable and difficult to navigate. And there are procedures that will remove excess skin. And I think that that is incredible growth area. And we will see a growth in the kind of like med spa, skin removal, surgery situations.
53:53Emily Oster:Okay. Those are big surgeries. That's no joke.
53:55Perry Wilson:I realized that, but I'm still going to go for investing there. Okay. So that's one place.
54:02Emily Oster:I'm wondering about like our food industrial complex, right? Like I walked down this supermarket and there's like 80 different cereals. Like, are they scared? Is Kellogg's like, uh-oh.
54:11Perry Wilson:I think they are, yeah. So I think there's like two interesting sort of places that may be affected by this. One is like the snack food complex, right? If you think about what is gonna go from people's meals, I think snacks are likely to go some. And so I think we are already seeing impacts on snack foods. We're already seeing restaurants think about, hey, can we lower the portion sizes, right? Like for a restaurant, that's good. but you'd rather give people smaller portions because it's less expensive for you. And so we sort of, I think we may see a little shrinking. The place I think the other, the growth area in the other direction is protein snacks, right?
54:48Perry Wilson:If you think all of a sudden people are eating fewer calories, but they need a lot of protein, that's where you need your protein popcorn, your protein, you know, fish.
54:56Emily Oster:I'm so glad there wasn't enough protein snacks. There weren't enough protein snacks.
55:02Perry Wilson:And now the David Bar is coming for you. And so I think it's a sort of protein growth, carbohydrate snack decline. And so I do think that there's some movement in that space. I'm not exactly sure how I would invest on that or on any of my ideas. It's a good thing I don't have a lot of money to invest in my stupid investment ideas.
55:20Emily Oster:What about medicine with a capital M? I work in a hospital. I see patients in a clinic. Do you think that this can be transformative enough that I won't have as many kidney disease patients? I won't have as many heart disease patients. I mean, people have to die of something, I guess, right? Eventually, maybe it happens when they're older.
55:39Perry Wilson:Yeah, I mean, those are much slower moving changes. I think there's an interesting overlap there with the question of kind of the cost of these drugs. So these drugs are right now quite expensive. The prices have been coming down a lot, but they're still expensive. They're covered in sometimes intermittently by insurance. but one of the arguments for expansion of access to these medications, especially if we think about like a government payer, is that they will lower people's risk of other things. So, you know, you, Perry, are expensive. Somebody comes to see you, you know, it costs money. If fewer people have kidney disease because of their GLP-1s, it actually sort of offsets the cost of the GLP-1 to some extent.
56:23Perry Wilson:And depending on how big those effects are, we could see these medications, even though they are relatively expensive, and even if they stayed relatively expensive, we could see them cause overall cost savings in the healthcare market, which would be in part a reduction in need for doctors, but probably would be more significantly a reduction in use of other medications. So if you are a maker of a statin, this may be more bad for you than if you are someone who treats people with a heart attack, which is still something people are going to die of. Just maybe they'll die of them later.
56:56Emily Oster:One of the things that this ties into is, okay, we've sort of come to the point where we're like, these drugs are going to be in the fabric of our society, whether they're injectable or oral. We've said that you're going to be potentially taking them in some form or another for a long period of time. And a lot of people are worried about that saying like, you know, but we don't know what might happen, right? That sure, they seem to be working great now, but how do we know that if you're not on it for 30 years, it causes cancer or something like that? What data do we have to either reassure people or terrify them?
57:31Perry Wilson:Yeah, I mean, I think that the short answer is we don't, we can't really fully reassure people about that. You know, these first, when you said at the top, the first of these drugs is approved in 2005. People have been on this for diabetes for a long time. We haven't seen those kind of signals, but it's not exactly the same drugs. It's not at the same dosing levels, not for the same indication. So, you know, if you want to know what is the impact of these drugs in 30 years, you need to wait for 30 years. And, you know, we ultimately, like with almost any new drug, you've got to weigh the sort of known value of the medication against these kind of long-term potential risks.
58:07Perry Wilson:I actually think that sort of cost-benefit calculation is always an important part of these choices, but is probably relevant to the extent that some of the usage of these medications is not for indicated purposes, right? So we are definitely seeing use of GLP-1s in populations where people do not need them to treat metabolic disease, right? This is a medication that is intended to treat obesity or diabetes or complications of obesity. That is the indication for the medication. It's not a medication intended to move your BMI from 21 to 14 or 17, which is some of how it seems like it's being used, particularly in celebrity circles.
58:52Perry Wilson:And it's always hard to know who's losing weight for what reason. But there's a kind of the part of the cautionary conversation, it feels important to me, is the one where people are sort of using these effectively really off-label in a way that changes the conversation around what is an appropriate physical appearance for someone. And we lost a little bit of what I thought was probably a good move towards the idea that people could be different sizes and not just a size two.
59:23Emily Oster:Thank you for saying that. It's worth noting that fat has value. It is metabolically important. It is hormonally active tissue in a good way. And being underweight, however you get to being underweight with this drug or any other way, can have actual long-term health consequences. And there's any number of studies that actually show that sort of the sweet spot for body weight in terms of longevity and especially resilience against disease. So when you do get sick, you know, being able to sort of bounce back from that is probably in the normal weight range, you know, a BMI between 20 and 25 or so.
1:00:06Emily Oster:If you're pushing below that, you are starting to stress your body a little bit more. I just have to say, I have a patient who is telling me that she was taking one of these drugs to get back to her original weight. And I said, what was your original weight? And she said, seven pounds, 14 ounces.
1:00:22Perry Wilson:That's too much. I mean, I will say I've started to see discussion. You know, people have started to talk about this a lot in the like endurance sports community, because it is, of course, true. if you are like a runner, that there is some value to being smaller because you're moving less bulk. But actually, these medications are really bad for performance. And some of these sort of discussions, I think, have gotten like a little confused and also ultimately probably not very good for either people's health or in that particular case for, you know, running fast. So if you want to run fast, this is maybe not for you.
1:01:00Emily Oster:Not for everyone.
1:01:01Perry Wilson:Not for everyone. Yeah. All right. So Perry, before we get to our final feelings on this, let's talk about sort of where this is going and both in terms of the medications and in terms of kids. So on the question of the medications, you know, my sense is we're just going to keep seeing new versions of this come out that are, you know, better in a variety of dimensions, easier to dose oral versus injected, more weight loss in 28 % versus 20%. Those are the two big dimensions. What other dimensions are we going to see innovation?
1:01:31Emily Oster:Cost. Things will get cheaper. But yeah, honestly, I think in terms of weight loss, up at 28%, I think we're done. You're taking a 200-pound person and bringing them down to 140 pounds. I don't think we need to improve too much on that. So yeah, you're going to see cost differences as things come off patent, and then the orals are going to be somewhat game-changing. And there may be tweaks that improve side effect profile and things like that. We'll see that. The question of kids is really fascinating. So the landscape right now is that Ozempic itself does have FDA approval for kids 12 and up.
1:02:09Emily Oster:It's the only one. The rest start at age 18. I'm ambivalent about this because for one thing, kids are kids. They're not just small adults. They're their own things. They're growing. And especially for kids who are growing, like calories are important for that. And stunting a kid's growth is a permanent thing that can happen. So I'm very nervous about this. On the other hand, there is an argument to be said that like, you know, the fat tissue that you add as a child does not really go away ever. In fact, as you lose weight, a lot of those cells are just shrinking, not necessarily dying off or evaporating.
1:02:49Emily Oster:Is it a possibility that establishing some habits with the use of a drug like this in your youth when you're sort of forming your relationship with food could be beneficial in the long term? Or on the other hand, could it be entirely harmful? Like I am really up in the air about this.
1:03:03Perry Wilson:You're in a rabbit hole. Yeah, me too. I am.
1:03:06Emily Oster:I don't know.
1:03:07Perry Wilson:I think it's really complicated because you're right. I think our habits, our taste for foods are formed when we our kids. And that is an argument for forming those habits. Well, I mean, I guess my, the thing I would say for sure is this should not be a first line. Like I would really like us to think more carefully about how we can help families develop good food habits with their kids, whether that's like better school lunch programs, better supports, or like all kinds of things I would like to do before we get to like, let's ever give everybody a Zempic when they're 12, which just feels like, you know, probably there are some people who will benefit from that and it'll be good to have that as an option, but I don't want it to be the first line.
1:03:50Perry Wilson:And I don't think that that's a good idea. Okay. All right. Okay, Perry, we're going to end with our segment in which we give our yes or no. And I am going to insist that we call this segment smash or pass. All right.
1:04:04Emily Oster:I am on board. And for those of you from a generation that is not X, you can Google what that means.
1:04:11Perry Wilson:All right. So Perry, GLP-1 smash or pass? Smash.
1:04:16Emily Oster:Definitely transformative drugs will be with us for a long time, changing a lot of outcomes. Not for everyone, as you say, but yeah, definite smash for me. How about you?
1:04:26Perry Wilson:Yeah, I'm a smash if it's the right person on this one. I think for some people, for many people, this is going to be a really game changing solution. It's not for everyone, but I think it's going to represent a really important part of the health landscape in the next several decades.
1:04:43Emily Oster:All right. After the break, we'll get to your question. This episode is brought to you by Spreaker, the platform responsible for a rapidly spreading condition known as podcast brain. Symptoms include buying microphones you don't need, explaining RSS feeds to confused relatives, and saying things like, sorry, I can't talk right now, I'm editing audio. If this sounds familiar, you're probably already a podcaster. The good news is Spreaker makes the whole process simple. You record your show, upload it once, and Spreaker distributes it everywhere people listen. Apple Podcasts, Spotify, and about a dozen apps your cousin swears are the next big thing.
1:05:20Emily Oster:Even better, Spreaker helps you monetize your show with ads, meaning your podcast might someday pay for, well, more microphones. Start your show today at Spreaker.com. Spreaker, because if you're going to talk to yourself for an hour, you might as well publish it.
1:05:36Perry Wilson:What if mind control is real? If you could control the behavior of anybody around you,
1:05:41Emily Oster:what kind of life would you have? Can you hypnotically persuade someone to buy a car? When you look at your car, you're going to become overwhelmed with such good feelings.
1:05:50Perry Wilson:Can you hypnotize someone into sleeping with you?
1:05:52Emily Oster:I gave her some suggestions to be sexually aroused.
1:05:56Perry Wilson:Can you get someone to join your cult? NLP was used on me to access my subconscious.
1:06:01Emily Oster:NLP, aka Neuro Linguistic Programming, is a blend of hypnosis, linguistics, and psychology. Fans say it's like finally getting a user manual for your brain. It's about engineering consciousness. Mind Games is the story of NLP. its crazy cast of disciples,
1:06:18Perry Wilson:and the fake doctor who invented it at a New Age commune and sold it to guys in suits. He stood trial for murder and got acquitted. The biggest mind game of all? NLP might actually work.
1:06:32Emily Oster:This is wild. Listen to Mind Games on the iHeartRadio app, Apple Podcasts, or wherever you get your podcasts. The more you listen to your kids, the closer you'll be. So we asked kids, what do you want your parents to hear?
1:06:47Perry Wilson:I feel sometimes that I'm not listened to. I would just want you to listen to me more often and evaluate situations with me and lead me towards success. Listening is a form of love. Find resources to help you support your kids and their emotional well-being at SoundItOutTogether.org. That's SoundItOutTogether.org.
1:07:07Emily Oster:Brought to you by the Ad Council and Pivotal.
1:07:09Perry Wilson:Hi, everyone.
1:07:10Emily Oster:I'm Cheryl Strayed, author of Wild and Tiny Beautiful Things. I'm excited to share that I have a new podcast called Mind Over Mountain. In each episode, I interview athletes, adventurers, and adrenaline seekers to discuss the inner landscapes and life experiences that informed and inspired their extraordinary feats. I also bring a bit of advice into the mix so we, too, can better understand how to face our own seemingly insurmountable challenges. Do you know what I'm going to do? I'm going to pull out what you already have inside. We're coming into this world fighting for our lives. All I'm going to do is pull out what you already got inside.
1:07:47Emily Oster:We're there to support and celebrate each other. And that's not like a your story versus my story. You're going to walk up and over that dang mountain. You're not just going to put your mind over it. Yep, yep, exactly. And if I can't walk up and over it, I'm going to go through it. Listen to Mind Over Mountain every Thursday on the iHeartRadio app, Apple Podcasts, or wherever you get your podcasts.
1:08:11Perry Wilson:all right perry mailbag question of the week uh is a personal one what is the dumbest thing
1:08:19Emily Oster:or greatest thing in your fridge right now i have such a good dumb thing and like for a podcast about wellness just beep this entire segment don't listen to what i'm about to say but you can get from Amazon or any other online store. Do you know the cheese powder that goes in mac and cheese, like the orange? Of course, yes. Okay.
1:08:42Perry Wilson:Oh my God.
1:08:42Emily Oster:You can get a bulk container of that.
1:08:45Perry Wilson:Ew, Perry, that's so gross.
1:08:47Emily Oster:Okay. Okay, wait. Here's what you can do with it. A, you can add it to your mac and cheese. It's that much cheesier. But wait, there's more. You can make popcorn and then you can put that stuff on your popcorn. That does sound good. That's good. Yeah. You can make pasta sauces out of it. It's so good. It is so bad for you. Please don't do this anymore.
1:09:11Perry Wilson:Perry, why does it have to be in your refrigerator? This is what I don't understand.
1:09:15Emily Oster:So actually, no, it's in my cabinet. But now it's like, why shouldn't it? It's cheese. Like, it probably should be in my refrigerator.
1:09:21Perry Wilson:No, I don't think that stuff is cheese, my friend. Sorry to tell you.
1:09:24Emily Oster:It's microplastics. What's the dumbest thing in your refrigerator? I'm so curious about this because Emily's like the healthy one for those of you who don't know both of us. So it's going to be like, oh, I got tomato juice, but it was like a normal amount of sodium.
1:09:40Perry Wilson:No, I like sodium. I drink a lot of sodium, please. I drink like – I put element in my water in the morning. I'm like very into sodium. We can talk about that another time. Pro sodium, all right. I have a kind of peanut butter I really like. It's called One Trick Pony. I am, peanut butter is like one of my core food groups. And unfortunately they have had a jar shortage. And so the only way to purchase this online right now is in a nine pound tub. And so I have a nine pound tub of peanut butter that's on the fridge though.
1:10:11Emily Oster:That's a lot of peanut butter.
1:10:13Perry Wilson:It's a lot of peanut butter. I go through it surprisingly quickly.
1:10:18Emily Oster:That's it for us today. Stick with us next week when we'll ask, What's the deal with red light therapy?
1:10:25Perry Wilson:Wellness Actually is produced in association with iHeart Media. Our senior producer is Tamar Avishai. Our executive producer at iHeart is Jennifer Bassett. Our theme music is by Eric Deutsch. And our content is for educational purposes only.
1:10:39Emily Oster:If you like the show, help other people find us. Leave a rating and review on Apple Podcasts or your podcatcher of choice. And help us spread the word about the show. Don't give the TikTokers all the power. And don't forget, we want to hear from you. Head over to wellnessactually.fm and leave us a question for our mailbag or suggest a topic for a future show. We'll let the influencers have the last word. I saw a commercial for Weight Watchers. We're doing GLP-1s now, which is Ozempic and stuff. That's like a karate dojo selling guns. You know what I mean? Like, it's not what it is. The latest breakthrough in self-defense, guns!
1:11:29Emily Oster:When Kohler, global design leader in luxurious kitchen and bath products, asked me to be their ambassador for timeless, elegant, durable cast iron, I said, I'm in. Soon after, I was in their Kohler, Wisconsin foundry, watching molten iron poured, enamel applied by hand, and the beautiful finished pieces ready to ship. Since 1883, Kohler cast iron has been crafted by incredible artisans, and seeing it firsthand gave me a whole new appreciation for their craftsmanship. Now, I'm proud to lend my stamp of approval to my favorite Kohler cast iron products for their durability, beauty, and enduring style.
1:12:11Emily Oster:Shop my curated pics at Kohler.com. As the Kohler cast iron ambassador, I say, long live cast iron. Peace to the planet. Charlamagne Tha God here. And listen, we are back. The Black Effect Podcast Festival is back in Atlanta on April 25th at Pullman Yard. Yeah. And the full lineup is nuts. We got the Grits and Eggs podcast. Deontay Kyle and Big Ice Cup Cat. We got Club 520 with Jeff Teague and the gang. Don't call me white, girl. Mona will be there. Keep it positive, sweetie, with Crystal Renee. We got reality with the king with Carlos King. And yes, Drink Champ will be in the building. plus you know we're gonna have a lot of guests so you need to join us and we got the black effect marketplace to pitch your podcast and everything you expect from the black effect podcast festival tickets are on sale right now go get yours at black effect.com slash podcast festival don't play yourself okay pull up
1:13:10Emily Oster:what if mind control is real if you could control the behavior of anybody around you What kind of life would you have? Can you hypnotically persuade someone to buy a car? When you look at your car, you're going to become overwhelmed with such good feelings. Can you hypnotize someone into sleeping with you? I gave her some suggestions to be sexually aroused. Can you get someone to join your cult? NLP was used on me to access my subconscious. Mind Games, a new podcast exploring NLP, a.k.a. Neurolinguistic Programming. Is it a self-help miracle, a shady hypnosis scam, or both. Listen to Mind Games on the iHeartRadio app, Apple Podcasts, or wherever you get your podcasts.
1:13:50Emily Oster:Then she says, have you seen a photo of my son? And I'm like, who is this person?
1:13:55Perry Wilson:Welcome to the Boys and Girls podcast. Arranged marriage is basically a reality show and you're auditioning for your soulmate. And who's judging? Only your entire family? I sacrificed myself to this ancient tradition, hoping to find love the right way. And instead, I found chaos, comedy, and a lot of cringe. Listen to Boys and Girls on the iHeartRadio app, Apple Podcasts, or wherever you get your podcasts.
From the publisher
This week, Emily and Perry discuss GLP-1s, those blockbuster weight-loss drugs that have taken the world by storm -- and not just what you already know about them. From the origins in Gila monster venom to the surprisingly long history of their use, they explore their effectiveness, side effects, lingering questions about long-term usage, and the weird knock-on effects in both the brain (libido?) and our society (protein water?). These drugs are here to stay, so let's understand them from every angle.
Plus: RFK vs. Dr. Mike, a concerning Surgeon General pick, and unsurprising data around football head injuries.
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