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[00:00:00.160 --> 00:00:02.960] Wait, have I ever told you about steakhouse or gay bar?
[00:00:03.280 --> 00:00:04.240] Hang on.
[00:00:04.240 --> 00:00:06.160] I want to look it up just because it's yep.
[00:00:06.160 --> 00:00:06.480] Is it?
[00:00:06.480 --> 00:00:07.040] There we go.
[00:00:07.040 --> 00:00:07.760] What does it have?
[00:00:07.760 --> 00:00:09.360] Uh, magic castle.
[00:00:09.360 --> 00:00:10.720] Oh, it's gotta be steakhouse.
[00:00:10.720 --> 00:00:11.680] Yeah, correct.
[00:00:12.000 --> 00:00:13.600] Stockyards.
[00:00:13.600 --> 00:00:14.800] Oh, that's a gay bar.
[00:00:14.800 --> 00:00:16.480] Incorrect steakhouse.
[00:00:16.480 --> 00:00:16.960] What?
[00:00:17.280 --> 00:00:19.120] Excelsior.
[00:00:19.120 --> 00:00:21.440] That's either a bad steakhouse or a bad gay bar.
[00:00:21.440 --> 00:00:22.320] Oh, gay bar.
[00:00:22.320 --> 00:00:22.960] Fuck yes.
[00:00:22.960 --> 00:00:24.160] Oh, juicy Lucy's.
[00:00:24.160 --> 00:00:24.960] That's a steakhouse.
[00:00:24.960 --> 00:00:26.400] Sick cock in my asshole.
[00:00:26.400 --> 00:00:27.600] Oh, steakhouse.
[00:00:27.920 --> 00:00:28.320] Wow.
[00:00:28.320 --> 00:00:29.840] Charlie Brown's.
[00:00:30.160 --> 00:00:31.360] I'm not touching that.
[00:00:31.360 --> 00:00:32.320] I'm not touching that.
[00:00:32.320 --> 00:00:33.680] Let's move on.
[00:00:34.000 --> 00:00:35.040] It was a steakhouse.
[00:00:35.040 --> 00:00:36.720] Aubrey, why can't we do a fun episode?
[00:00:36.720 --> 00:00:39.760] Why can't we just do this for an hour instead of talking about Ozempic?
[00:00:50.800 --> 00:00:57.200] Welcome to Maintenance Phase, the podcast that works in the short term, but has never been tested for more than two years.
[00:00:58.800 --> 00:01:00.480] That's kind of true, actually.
[00:01:00.480 --> 00:01:01.120] Accidentally.
[00:01:01.360 --> 00:01:04.880] That is a pretty accurate thing to say about our podcast.
[00:01:04.880 --> 00:01:06.960] It hasn't been tested in long term.
[00:01:06.960 --> 00:01:08.560] People go back to where they were.
[00:01:09.120 --> 00:01:10.240] I'm Michael Hobbs.
[00:01:10.240 --> 00:01:11.520] I'm Aubrey Gordon.
[00:01:11.520 --> 00:01:18.080] If you would like to support the show, you can do that at patreon.com/slash maintenance phase, or you can subscribe on Apple Podcasts.
[00:01:18.080 --> 00:01:20.160] It's the same audio content.
[00:01:20.160 --> 00:01:21.040] Michael.
[00:01:21.040 --> 00:01:23.760] Aubrey, let's start with your nervousness.
[00:01:24.240 --> 00:01:25.440] My nervousness.
[00:01:25.440 --> 00:01:26.560] We're going to talk about it.
[00:01:26.560 --> 00:01:28.400] Your complicated feelings.
[00:01:28.400 --> 00:01:36.560] So today, we are talking about Ozempic Wegovi and their active ingredient, semaglotide.
[00:01:36.560 --> 00:01:38.160] Wait, I thought it was semaglutide.
[00:01:38.160 --> 00:01:42.480] I thought it was two, and then I heard a million doctors say semaglotide.
[00:01:42.480 --> 00:01:43.920] Semaglatide?
[00:01:43.920 --> 00:01:45.600] Doesn't that seem wrong?
[00:01:45.600 --> 00:01:46.320] Yeah, but sure.
[00:01:46.320 --> 00:01:49.760] I mean, they're made up words anyway, and then on some level, every word is made up, so whatever.
[00:01:49.760 --> 00:01:51.360] Well, listen, from Mr.
[00:01:51.360 --> 00:01:52.720] Denaumant.
[00:01:54.960 --> 00:01:58.880] It's a safe space for creative pronunciation.
[00:01:58.880 --> 00:02:04.360] The thing is, so much of the fucking feedback to this show is about my pronunciations of words.
[00:02:04.600 --> 00:02:08.280] No one ever wants to give me feedback on the content of the show.
[00:02:10.200 --> 00:02:11.320] Michael.
[00:02:12.200 --> 00:02:15.160] This episode is actually a little different than how we usually do things.
[00:02:15.160 --> 00:02:15.640] Yes.
[00:02:15.800 --> 00:02:19.640] I'm going to walk us through the drug and its origins.
[00:02:19.640 --> 00:02:26.600] You're going to walk us through the clinical trials into this sort of class of drugs.
[00:02:26.920 --> 00:02:34.040] And then we're going to talk about what I think is the thorniest part of all of this, the discourse around those drugs.
[00:02:34.040 --> 00:02:35.480] The discourse.
[00:02:35.480 --> 00:02:37.160] This is a big one.
[00:02:37.480 --> 00:02:40.360] It feels like a really high-stakes conversation.
[00:02:40.360 --> 00:02:47.240] So I'm curious about, for you, what are some of the things that you're sort of like bringing to that?
[00:02:47.240 --> 00:03:03.720] I think my weirdness with this episode is the culmination of my weirdness with every episode of the show, where both of us are interested in public health, in the kinds of things that are prescribed, how drugs get approved, what they mean societally.
[00:03:03.720 --> 00:03:21.160] Whereas because Americans have been trained by health media for our entire lives to see everything through an individualistic lens, we are going to be spending basically this entire episode talking about the narratives around Ozempic and Wagovi.
[00:03:21.160 --> 00:03:30.360] We have this new generation of weight loss drugs that as of now appear to deliver much more weight loss than any previous generation of weight loss drugs.
[00:03:30.360 --> 00:03:37.240] And we've had this immediate, huge wave of media being like, is this the end of obesity?
[00:03:37.240 --> 00:03:40.040] Does this invalidate body positivity?
[00:03:40.040 --> 00:03:50.160] And like being a dietitian in the age of Ozempic and all this just insufferable kind of endpoint prediction stuff based on very little information.
[00:03:50.480 --> 00:04:02.320] And what we are interested in and like what we have been talking about behind the scenes nonstop for the last like couple months is like how poisonous these narratives are.
[00:04:02.320 --> 00:04:06.080] But what people tend to hear is like individual health advice.
[00:04:06.080 --> 00:04:10.320] Mike and Aubrey think you shouldn't take Ozempic or Mike and Aubrey think you should take Ozempic.
[00:04:10.720 --> 00:04:13.920] And like that is just not something that we are interested in.
[00:04:13.920 --> 00:04:20.400] We've said on the show before that if you want to lose weight and you want to do keto or a cleanse, you can do that.
[00:04:20.800 --> 00:04:22.240] We don't have opinions on that.
[00:04:22.240 --> 00:04:22.800] Yeah, totally.
[00:04:22.800 --> 00:04:28.160] And if people don't want to do that, they also shouldn't be pressured to do so.
[00:04:28.160 --> 00:04:32.800] And I just know that this is like a big topic for a lot of people, right?
[00:04:32.800 --> 00:04:42.400] For me included, both because I'm engaging with all of this media and fat people writ large are engaging with all this media that is like, could we finally be rid of fat people?
[00:04:42.400 --> 00:04:46.640] Is like the framing of a lot of this conversation.
[00:04:46.640 --> 00:04:57.440] But like on top of that, I mean, we've talked about this before on the show that one of my very best friends was diabetic and passed away because she couldn't access treatment.
[00:04:57.440 --> 00:04:58.080] Yeah.
[00:04:58.080 --> 00:04:58.560] Right.
[00:04:58.560 --> 00:05:00.880] That was like facilitated by a lot of things.
[00:05:00.880 --> 00:05:06.080] It was facilitated by capitalism and anti-blackness and transphobia and lots of things.
[00:05:06.080 --> 00:05:17.040] But it was also facilitated by our sort of cultural disregard and disdain for people who have diabetes or any health conditions that we deem as quote unquote doing it to yourself.
[00:05:17.040 --> 00:05:21.680] For many folks, this is like a matter of body image, which is really tender and personal.
[00:05:21.680 --> 00:05:28.400] For other folks, for people who are on this medication for their diabetes, this can very literally be a matter of life and death.
[00:05:28.400 --> 00:05:28.800] Right.
[00:05:28.800 --> 00:05:29.280] Right.
[00:05:29.280 --> 00:07:02.640] We're talking about like a wide range of big feelings and it's like understandable right this is one of the most intense and sort of widespread moments of body related discourse we've had in quite some time right people who are taking this for weight loss are told that they're sort of taking the easy way out which they absolutely are not and which also presumes that people are fat because they don't try hard enough right right and when those people are fat they're often being forced into this kind of weight loss in order to access healthcare treatments surgeries other like super basic needs right right this just feels like huge that way i think a fun bit for the show would be to just do a bunch of table setting and like caveats and then just never get to the topic another thing we want to say right off the bat we have gotten dangerously close to an entire episode of caveats we're working toward it so for part one we're just going to talk about the drug itself we're going to talk about semaglotide which is the active ingredient in ozempic and we govi ozempic and wegovi are injections that are produced by novo nordisc which is a big pharmaceutical company they're part of a group of medications that are called glp1 agonists glp1 helps regulate our hunger and satiety signals and production of other hormones like insulin there are other glp1 agonists sort of on the market most of them approved for diabetes treatment.
[00:07:02.640 --> 00:07:08.960] Those are Rebellsis, Majaro, and there are about another dozen that are sort of coming down the pipeline.
[00:07:09.280 --> 00:07:13.040] Semaglotide has been on the market as a treatment for type 2 diabetes in the u.S.
[00:07:13.000 --> 00:07:15.760] since 2018 under the name ozempic.
[00:07:15.760 --> 00:07:21.200] When it's prescribed for weight loss, it's prescribed under the name Wegovi.
[00:07:21.520 --> 00:07:24.000] It's the same thing, they're just different doses.
[00:07:24.000 --> 00:07:28.960] Interestingly, the weight loss one requires a slightly higher dosage of samaglatide.
[00:07:29.520 --> 00:07:33.520] So this drug started to be sort of studied.
[00:07:34.000 --> 00:07:42.000] Its glimmers begin in 1984 with an endocrinologist at the University of Toronto.
[00:07:42.000 --> 00:07:42.960] His name is Dr.
[00:07:42.960 --> 00:07:49.920] Daniel Drucker, and he discovers a new hormone in humans, which is GLP-1.
[00:07:49.920 --> 00:07:53.760] It's called glucagon-like peptide 1.
[00:07:53.760 --> 00:07:54.880] Girl glucagon.
[00:07:55.040 --> 00:08:07.200] As he and other researchers tried to figure out how GLP-1 functioned in the human body, it starts to show real promise as a treatment for type 2 diabetes, but they have this problem.
[00:08:07.520 --> 00:08:12.720] GLP-1 sort of disappears from your system very quickly.
[00:08:13.200 --> 00:08:17.120] So it makes it really hard to study, much less sort of reproduce it.
[00:08:17.120 --> 00:08:23.920] So they start looking for alternate sources of GLP-1 that might last a little longer than the human version, right?
[00:08:24.400 --> 00:08:28.960] And that's when the Gila monster comes in.
[00:08:28.960 --> 00:08:29.360] Oh.
[00:08:29.520 --> 00:08:33.280] Mike, have you ever heard of the Gila monster?
[00:08:33.280 --> 00:08:35.120] Yeah, they're like a cute little lizard.
[00:08:35.120 --> 00:08:39.840] They're like a kind of like a thick, like robust lizard.
[00:08:39.840 --> 00:08:42.240] I did not know about them before this episode.
[00:08:42.240 --> 00:08:43.600] I didn't know a thing about them.
[00:08:43.600 --> 00:08:46.000] They're the largest lizard in North America.
[00:08:46.000 --> 00:08:47.360] They're almost two feet.
[00:08:47.360 --> 00:08:50.240] I've never seen one in real life, but I've seen them in zoo books and they're really cute.
[00:08:50.240 --> 00:08:51.360] Well, listen, Dr.
[00:08:51.360 --> 00:08:55.120] Drucker had one shipped to him in Toronto.
[00:08:55.120 --> 00:08:55.600] Okay.
[00:08:56.240 --> 00:09:05.080] Because it goes through long periods without food, and it has the ability to slow down its appetite and metabolism.
[00:09:05.080 --> 00:09:05.720] Okay.
[00:09:05.720 --> 00:09:09.320] And Drucker wanted to know how they were able to do that.
[00:09:09.320 --> 00:09:21.480] And he discovers that those Gila monsters have genes for something called Extendin 4, which, when sort of synthesized in a lab, eventually became ozempic.
[00:09:21.480 --> 00:09:24.760] How ironic that a thick lizard gave us thin women.
[00:09:24.760 --> 00:09:25.800] Interesting.
[00:09:26.120 --> 00:09:27.000] Interesting.
[00:09:27.000 --> 00:09:46.280] So researchers don't totally know the mechanism for what makes GLP-1 agonists work the way that they do, but we do know that semaglotide sort of mimics that GLP-1 hormone that is, again, released after you eat.
[00:09:46.280 --> 00:09:52.440] It's part of what makes you feel full, and it's part of what signals your brain that it's time to stop eating.
[00:09:52.440 --> 00:09:58.280] And so it works by you end up eating less because you just basically feel full after each meal.
[00:09:58.280 --> 00:09:58.600] Yeah.
[00:09:58.600 --> 00:10:00.360] So like it triggers your satiety hormones.
[00:10:00.360 --> 00:10:05.480] So like ordinarily you'd be hungry again two hours after breakfast, but now it's like three or four hours after breakfast.
[00:10:05.480 --> 00:10:10.200] And so over the course of a day, you just end up eating like, I don't know, 20, 30% less.
[00:10:10.200 --> 00:10:10.680] Yes.
[00:10:10.680 --> 00:10:14.440] And on top of that, it's holding that food longer in your stomach.
[00:10:14.440 --> 00:10:18.440] So you are physically full for a longer period of time, right?
[00:10:19.080 --> 00:10:23.000] And it's triggering a release of insulin.
[00:10:23.000 --> 00:10:29.880] And also, it may help grow pancreatic beta cells, which are the cells that produce and release insulin.
[00:10:29.880 --> 00:10:34.840] So it's not just that it helps you release insulin in the short term.
[00:10:34.840 --> 00:10:38.440] It's also sort of like building up your ability to release insulin in the middle.
[00:10:38.520 --> 00:10:38.920] Oh, interesting.
[00:10:38.920 --> 00:10:39.880] So it's like flexing a muscle.
[00:10:39.880 --> 00:10:41.960] It's actually like building the muscle that secretes insulin.
[00:10:42.120 --> 00:10:42.840] It seems like it.
[00:10:42.840 --> 00:10:43.960] It seems like it might be.
[00:10:44.120 --> 00:10:51.520] The results for people with diabetes in clinical trials are really incredible.
[00:10:52.080 --> 00:10:58.800] So for diabetic people, the most important measure of your blood glucose is your A1C.
[00:10:58.800 --> 00:11:08.160] That's a measure of the amount of hemoglobin in your blood that reflects your blood glucose levels over the last like few months.
[00:11:08.400 --> 00:11:17.200] Most guidance for people with type 2 diabetes suggests that they should keep their A1C below 7 to minimize complications.
[00:11:17.200 --> 00:11:25.840] But people whose blood sugar isn't well managed can have A1Cs that are like 10, 11, 12, 13, like really high.
[00:11:25.840 --> 00:11:35.600] It can lead to damage to that person's eyes, including possible blindness, their kidneys, including kidney failure, to their nerves and to their heart.
[00:11:35.760 --> 00:11:42.880] With the introduction of these GLP-1 agonists, the results are kind of miraculous.
[00:11:43.360 --> 00:11:55.360] There are stories that are told about the initial presenting of the research on these at the American Diabetes Association conference, and people were weeping and gave it a standing ovation.
[00:11:55.360 --> 00:11:55.840] No, I.
[00:11:56.400 --> 00:12:02.720] Because what they're talking about is people whose A1Cs went from like 11 to 7, right?
[00:12:02.720 --> 00:12:12.160] From like really heightened, urgent risk down to like a pretty safe range just with this one drug, right?
[00:12:12.480 --> 00:12:21.760] I do think one of the fundamental like difficult things to process about any of these kinds of health conditions is that, like, we all kind of hate pharmaceutical companies.
[00:12:21.760 --> 00:12:26.960] Like, under a system of capitalism, it's like these are big global profit-maximizing entities.
[00:12:26.960 --> 00:12:31.080] But then, on the other hand, they deliver a product that is genuinely life-saving.
[00:12:31.080 --> 00:12:31.400] Yeah.
[00:12:31.400 --> 00:12:35.640] I know we just get kind of weird whenever people like praise pharmaceutical companies.
[00:12:29.920 --> 00:12:36.520] I'm like, I don't know about that.
[00:12:36.840 --> 00:12:41.720] But then, whenever people overly criticize pharmaceutical companies, I'm also like, I don't know either.
[00:12:41.720 --> 00:12:48.120] So, in the trials for Ozempic, they start noticing pretty significant weight loss.
[00:12:48.120 --> 00:12:52.680] And researchers start going, well, what if we could just use this as a weight loss drug?
[00:12:52.680 --> 00:12:54.520] So, they created Wegovi.
[00:12:54.520 --> 00:12:56.760] It's the same drug at a higher dose.
[00:12:56.760 --> 00:13:00.280] It uses more of the active ingredients, semaglatide.
[00:13:00.280 --> 00:13:03.720] And because of that, it costs more.
[00:13:03.720 --> 00:13:08.120] Diabetic version hovers at around $900 a month.
[00:13:08.120 --> 00:13:09.560] And it costs more for weight loss.
[00:13:09.560 --> 00:13:14.680] It costs like $1,300 a month out of pocket, and most insurers do not cover it.
[00:13:14.680 --> 00:13:30.200] Not that, like, my main purpose with this show is to widen the availability of weight loss drugs, but like there is something fascinating about how we've gotten all this stuff about like the obesity epidemic is so bad, it's like killing our kids, and then it's like we get a drug that ostensibly treats it, and they're like, that's too expensive.
[00:13:30.200 --> 00:13:38.440] Yeah, it is really wild that this is an issue where we like talk out of both sides of our mouths constantly as a culture.
[00:13:38.760 --> 00:13:48.040] In a lot of ways, the experiences of people who are taking Wegovi for weight loss or Manjaro or Rebelsis or whatever the other ones are that are getting prescribed off-label, right?
[00:13:48.360 --> 00:13:52.920] That like a lot of folks are being told that they're like taking the easy way out.
[00:13:52.920 --> 00:13:54.280] Yeah, that's really bizarre.
[00:13:54.280 --> 00:14:01.600] That's the kind of rhetoric that reveals itself to be not about concern, not about your health.
[00:14:02.320 --> 00:14:06.520] Just about, I want you to suffer for looking the way that you look.
[00:14:06.520 --> 00:14:07.720] We're doing discourse, Aubrey.
[00:14:07.720 --> 00:14:08.040] We're doing this.
[00:14:08.200 --> 00:14:11.080] We're doing discourse, and we're not even into the discourse.
[00:14:11.240 --> 00:14:11.920] I know, we haven't weighiovovovov.
[00:14:12.120 --> 00:14:14.360] Michael, I know, I know.
[00:14:14.360 --> 00:14:17.680] I'm keeping my discourse powder dry, but here we are.
[00:14:14.680 --> 00:14:18.400] We're discoursing.
[00:14:18.960 --> 00:14:25.040] So Wegovi was approved for weight loss by the FDA in June 2021.
[00:14:25.360 --> 00:14:33.920] Almost as soon as Wegovi was approved for weight loss, both Wegovi and Ozempic went into shortage.
[00:14:34.320 --> 00:14:47.040] That impacts both people seeking the drug for weight loss and the people using it to manage their blood glucose for diabetes, because what happens is that Wegovi goes into shortage first, right?
[00:14:47.040 --> 00:14:48.640] That's the weight loss one.
[00:14:48.880 --> 00:14:56.720] And then doctors start prescribing Ozempic, the diabetes medication, off-label to people who want to start to lose weight.
[00:14:57.440 --> 00:15:00.480] Then that goes into shortage too.
[00:15:01.360 --> 00:15:10.240] So as we record this, Wegovi and Ozempic are both in shortage, according to the FDA's sort of drug shortage database.
[00:15:10.720 --> 00:15:26.560] When a drug goes on the FDA's shortage list, the FDA then allows what are called compounding pharmacies to mix up what is basically their own version of that drug without prior FDA approval or screening.
[00:15:27.120 --> 00:15:38.560] When Ozempic and Wegovi went into shortage, compounding pharmacies across the country started compounding their own versions of samaglatide.
[00:15:39.200 --> 00:15:46.720] Here's the problem: Novo Nordisk has patented the samaglatide molecule.
[00:15:46.720 --> 00:15:47.280] Oh.
[00:15:47.280 --> 00:15:51.840] And only they can produce it until 2032.
[00:15:51.840 --> 00:15:57.880] So the active ingredient simply isn't available to those compounding pharmacies.
[00:15:57.600 --> 00:15:58.120] Wow.
[00:15:58.320 --> 00:16:01.400] These compounding pharmacies are prescribing something.
[00:16:01.400 --> 00:16:03.800] They're calling it samaglatide.
[00:15:59.920 --> 00:16:04.040] Okay.
[00:16:04.680 --> 00:16:08.680] It's not ozempic and it's not we govie.
[00:16:08.680 --> 00:16:12.280] It might be a watered-down dose of those things.
[00:16:12.600 --> 00:16:16.120] It could be something called samaglatide sodium.
[00:16:16.120 --> 00:16:16.520] Okay.
[00:16:16.520 --> 00:16:24.280] It's called samaglatide, but it's used in lab animal experiments and is not cleared for use in humans.
[00:16:24.280 --> 00:16:33.960] Oh, that's like when people were taking like horse antibiotics that you could buy on Amazon because they couldn't get like human antibiotics because they're like roughly the same thing.
[00:16:33.960 --> 00:16:38.440] Well, except this is not roughly the same thing and is hazardous to humans' health.
[00:16:38.440 --> 00:16:43.480] Samaglatide sodium is not cleared for use in humans because it is bad for humans.
[00:16:43.480 --> 00:16:44.440] Oh, fuck.
[00:16:44.440 --> 00:16:52.600] And the third option is that it's something else entirely because this is in shortage and because there is less FDA oversight.
[00:16:52.920 --> 00:16:59.800] These compounding pharmacies are not required to tell anyone what's in the drugs that they are giving people.
[00:17:00.200 --> 00:17:01.720] This may sound niche.
[00:17:01.720 --> 00:17:04.280] These compounding pharmacies may sound niche.
[00:17:04.280 --> 00:17:13.960] This is every web advertisement you see that says Ozempic for $99 a month or $499 a month or whatever.
[00:17:14.280 --> 00:17:20.520] All of these, all of the little startups that are like, just call and talk to a doctor and you'll have it the next day.
[00:17:20.840 --> 00:17:25.800] All of that stuff is powered by compounding pharmacies.
[00:17:25.800 --> 00:17:26.920] No way.
[00:17:27.240 --> 00:17:39.320] So this got so bad, the compounding pharmacy stuff has gotten so bad that the FDA has issued a number of official warnings about this and specifically has warned against buying from these startups.
[00:17:39.320 --> 00:17:41.400] This is such a bizarre system.
[00:17:41.400 --> 00:17:42.840] It's so weird.
[00:17:42.840 --> 00:17:53.840] It's like there's a shortage of this drug, so we're just gonna like let people buy it from like weird fly-by-night carnival barker ass companies selling whatever the fuck on the internet.
[00:17:53.920 --> 00:17:55.360] We're not gonna regulate it at all.
[00:17:55.360 --> 00:18:00.080] There's not an enforcement mechanism beyond these letters so far, right?
[00:18:00.080 --> 00:18:05.040] Like they're not they're not doing more than that yet, at least not in reporting.
[00:18:05.040 --> 00:18:07.760] Do you have any sense of like when this could resolve itself?
[00:18:07.760 --> 00:18:11.680] Like as Novo Nortis said that they're massively ramping up production?
[00:18:11.680 --> 00:18:15.680] Basically the goalposts just keep getting moved for when the shortage will end.
[00:18:15.680 --> 00:18:17.680] You know, I checked a couple months ago.
[00:18:18.000 --> 00:18:20.000] It said it would be over by the fall.
[00:18:20.000 --> 00:18:22.400] I checked again, it said it would be over by the end of the year.
[00:18:22.400 --> 00:18:23.920] Oh, it's like self-driving cars.
[00:18:23.920 --> 00:18:25.280] It's always five years away.
[00:18:25.600 --> 00:18:27.040] Right on the horizon.
[00:18:27.360 --> 00:18:34.560] As we're talking about these compounding pharmacies, big weight loss companies are buying up these startups.
[00:18:35.360 --> 00:18:40.640] Weight Watchers bought one of these and their stock price jumped almost 60% in a day.
[00:18:40.640 --> 00:18:43.120] Oh, from like 12 cents to like 16 cents or something.
[00:18:43.360 --> 00:18:49.280] I mean, listen, Weight Watchers stock was not doing great, but a 60% increase is a 60% increase, you know?
[00:18:49.280 --> 00:18:51.280] They've gone from a limp to a gate.
[00:18:51.280 --> 00:19:16.080] And I would say, because the discourse around this is all focused on like the real housewives are taking it and frivolous rich people and celebrities are taking it, it makes the issue seem like it isn't incredibly pressing and important, particularly for people with type 2 diabetes, particularly for people who can't access healthcare and other basic needs at their current weight.
[00:19:16.320 --> 00:19:28.320] This is the other thing about this discourse that drives me utterly fucking bananas is that there's not meaningful acknowledgement of the straight-up income barriers to getting this medication.
[00:19:28.720 --> 00:19:41.480] That this is a shortage that is largely presumably created by people with the disposable income to pay out of pocket for a weight loss medication that almost no insurers are covering.
[00:19:41.480 --> 00:19:41.960] Right.
[00:19:41.960 --> 00:19:44.120] You and I have discussed this until we're blue in the face.
[00:19:44.120 --> 00:19:51.960] Like neither one of us wants to litigate individual behaviors, but like that is one that really doesn't sit right with me.
[00:19:51.960 --> 00:19:53.640] My views on this are also very contingent.
[00:19:53.640 --> 00:20:00.920] Honestly, like once we get to a point where these are super duper available, if you want to take one to lose 10 pounds, genuinely, I don't give a shit.
[00:20:00.920 --> 00:20:03.240] In the same way, I don't give a shit if you want to get a nose job.
[00:20:03.240 --> 00:20:05.480] Yeah, but like in time of a shortage.
[00:20:05.480 --> 00:20:05.960] The same thing.
[00:20:05.960 --> 00:20:07.400] There's an Adderall shortage.
[00:20:07.400 --> 00:20:10.680] If you're not prescribed Adderall, don't take Adderall right now.
[00:20:10.680 --> 00:20:16.920] If you don't need Sriracha, I've been doing my part in buying slightly less sriracha than usual.
[00:20:16.920 --> 00:20:21.720] Dude, the Sriracha shortage has been a big topic of conversation in our household.
[00:20:21.720 --> 00:20:22.360] Are you still doing it?
[00:20:22.360 --> 00:20:24.600] Can I cancel you for eating sriracha in a time of need?
[00:20:24.600 --> 00:20:25.480] We had a bottle.
[00:20:25.480 --> 00:20:27.000] It was about halfway done.
[00:20:27.160 --> 00:20:28.360] I got another one.
[00:20:28.360 --> 00:20:29.480] Hypocrite.
[00:20:29.480 --> 00:20:30.200] Totally.
[00:20:30.200 --> 00:20:32.040] You're hoarding sriracha.
[00:20:32.040 --> 00:20:33.640] One and a half bottles.
[00:20:33.640 --> 00:20:35.640] Come take them from my cold dead end.
[00:20:35.800 --> 00:20:37.000] No, I'm just kidding.
[00:20:37.320 --> 00:20:48.760] So, Michael, this is unusual for us, but this topic was so big and expansive that you and I both actually researched this one.
[00:20:48.760 --> 00:20:52.840] And I dug in on sort of the discourse side and the reporting side.
[00:20:52.840 --> 00:20:55.000] And you really dug in on the research side.
[00:20:55.000 --> 00:20:59.480] So can you walk us through just like, what do we know from the research?
[00:20:59.480 --> 00:21:10.040] This is a weird format break for us because ordinarily, like one of us researches and one of us listens, but like it would be odd to pretend that we haven't both been following this like obsessively for the last couple months.
[00:21:10.040 --> 00:21:10.440] Yes.
[00:21:10.440 --> 00:21:20.560] I have deliberately avoided the discourse because I find the discourse annoying, but I have been following the research and like I have a literal spreadsheet of like the various studies that have been done.
[00:21:20.880 --> 00:21:25.840] And for these drugs, there's actually a quite finite amount of information.
[00:21:25.840 --> 00:21:33.840] And I just for the love of God, just want to like walk through what we know and what we can expect from these drugs.
[00:21:33.840 --> 00:21:34.800] Yeah, sounds great.
[00:21:34.800 --> 00:21:50.320] So basically, the trials of samaglatide for weight loss are all grouped under this heading of the STEP trials, which is the samaglatide treatment effect in people with obesity, which should be step-o, but is actually step.
[00:21:50.320 --> 00:21:53.280] Stepo, what, the fifth Marks Brother?
[00:21:55.920 --> 00:22:01.280] And these are sort of classic pharmaceutical company randomized control trials.
[00:22:01.280 --> 00:22:02.720] They are global.
[00:22:02.720 --> 00:22:05.040] They comprise 5,000 people.
[00:22:05.040 --> 00:22:06.960] All of them are 68 weeks long.
[00:22:06.960 --> 00:22:08.240] One of them is a little bit longer.
[00:22:08.240 --> 00:22:09.280] We'll get to it.
[00:22:09.280 --> 00:22:12.240] They are funded by Novo Nordisk, of course.
[00:22:12.240 --> 00:22:16.000] And the way that they structure these, they sort of do it like moon missions.
[00:22:16.000 --> 00:22:18.960] You know, there's like Apollo 1 and Apollo 2.
[00:22:18.960 --> 00:22:27.120] These large pharmaceutical trials are like there's step one, step two, step three, and they break them down into like specific things that they want to know.
[00:22:27.120 --> 00:22:33.280] And step one, step two, step three are not different phases in the same study, right?
[00:22:33.280 --> 00:22:35.040] They are separate studies.
[00:22:35.040 --> 00:22:41.680] So step one is like the overall, just like we're going to give fat people samaglatide for weight loss.
[00:22:41.680 --> 00:22:45.040] Step two is the same thing, but on people with type 2 diabetes.
[00:22:45.040 --> 00:22:49.920] Step three is samaglatide with intensive behavioral therapy.
[00:22:49.920 --> 00:22:50.720] BLTs!
[00:22:50.960 --> 00:22:53.840] And then the rest are kind of like smaller shading.
[00:22:53.840 --> 00:23:01.080] So step four is they put people on samaglatide for a while and then they switch half of them to a placebo.
[00:23:01.240 --> 00:23:03.560] Step five is a two-year trial.
[00:23:03.560 --> 00:23:08.360] Step six and seven are the same thing, but they're done on Japanese, South Korean, and Chinese people.
[00:23:08.360 --> 00:23:13.720] And step eight is testing samaglatide versus one of the other GLP1s.
[00:23:13.720 --> 00:23:16.440] So it's samaglatide versus laraglotide.
[00:23:16.440 --> 00:23:33.000] So when you say step six and step seven are focusing on East Asian folks, it's worth mentioning that most of these trials for Wegovi in particular are just overwhelmingly white, as many diet studies are.
[00:23:33.640 --> 00:23:47.000] One of the sort of leading meta-analyses of studies involving over 11,000 participants was 80% white, 10% black, and 5% AAPI.
[00:23:47.000 --> 00:23:53.080] Although for diet studies, I mean, we both see diet studies that are like 97% white fairly frequently.
[00:23:53.080 --> 00:23:56.600] So like, it's funny, like 80% white, I'm like, ooh, not bad.
[00:23:57.560 --> 00:23:59.320] The bar is in hell.
[00:23:59.320 --> 00:24:03.960] Yeah, like by the standards of fucking diet research, it's like, oh, very diverse sample.
[00:24:04.440 --> 00:24:10.360] The results of these samaglatide trials are like quite consistent, like remarkably consistent.
[00:24:10.360 --> 00:24:17.720] So roughly 80% of people who take samaglatide lose some amount of weight, roughly 5% of their body weight.
[00:24:17.720 --> 00:24:23.400] And roughly half of people who take samaglatide lose 10 to 15% of their body weight.
[00:24:23.400 --> 00:24:27.240] So like a one in two chance of losing like a moderate amount of weight.
[00:24:27.240 --> 00:24:44.120] And then the biggest number and the thing that has like sent the entire like weight loss industry into overdrive on this is that roughly one-third of people who take samaglatide lose more than 20% of their body weight, which is roughly on par with like bariatric surgery.
[00:24:44.360 --> 00:24:50.000] And then another thing that is like a pretty big deal about these drugs is that like the results seem to hold up.
[00:24:50.320 --> 00:24:59.600] So there's one trial where people took samaglatide for two years, and like by the end of it, 36% of people had lost more than 20% of their body weight.
[00:24:59.600 --> 00:25:06.880] So for about a third of patients, they're losing maybe three times as much weight as previous interventions.
[00:25:06.880 --> 00:25:11.440] We should also note that there are pretty significant health effects of these drugs.
[00:25:11.440 --> 00:25:20.080] So even in the shorter-term trials, people have better blood pressure, they have better cholesterol, they have improved A1C levels.
[00:25:20.080 --> 00:25:29.200] We also, with the longer-term trials, we've seen modest, but also kind of big deal reduction in heart attacks and strokes.
[00:25:29.200 --> 00:25:31.440] So that's really exciting.
[00:25:31.440 --> 00:25:31.760] Yeah.
[00:25:31.760 --> 00:25:37.840] If there is a drug that people can take and they are less likely to die, I am pro that drug.
[00:25:37.840 --> 00:25:41.600] I actually looked this up that it's roughly in line with the effect of statins.
[00:25:41.760 --> 00:25:43.760] So this is genuinely like a big deal.
[00:25:43.760 --> 00:25:45.840] Like even if you take the weight loss stuff off the table.
[00:25:45.840 --> 00:25:46.320] Yeah.
[00:25:46.320 --> 00:25:49.040] We should also talk about the side effects.
[00:25:49.040 --> 00:25:52.880] The side effects of the drugs seem to be almost universal.
[00:25:52.880 --> 00:26:01.200] Some studies find, I think the lowest one I found was like 60% of people have like gastrointestinal symptoms, but then some of them are finding like 93% of people.
[00:26:01.200 --> 00:26:14.080] So it's like nausea, constipation, diarrhea, vomiting, the sort of tummy stuff that you would associate with like pretty significantly fucking with your like hunger and satiety hormones.
[00:26:14.080 --> 00:26:27.760] In addition to all of those side effects, there is sort of this whole class of side effects that get covered mostly in like beauty media and like gossip blogs like Ozempic Face.
[00:26:27.760 --> 00:26:29.600] Have you heard about Ozempic Face?
[00:26:29.720 --> 00:26:32.440] From you like 10 minutes ago, right when we started recording.
[00:26:32.600 --> 00:26:37.880] Looks some of us were trying to keep the illusion alive, Michael.
[00:26:38.520 --> 00:26:44.280] So it's basically just the appearance of aging when taking Ozempic.
[00:26:44.280 --> 00:26:46.200] And it's just the result of rapid weight loss.
[00:26:46.200 --> 00:26:48.840] However, you did it, it's not unique to Ozempic.
[00:26:48.840 --> 00:26:53.000] It's just when you lose a lot of weight really quickly, you end up with loose skin.
[00:26:53.000 --> 00:26:53.240] Right.
[00:26:53.240 --> 00:26:55.720] And some of that loose skin will be on your face.
[00:26:55.720 --> 00:26:59.000] And that is also the same kind of thing that happens when people age.
[00:26:59.000 --> 00:26:59.880] So you look older.
[00:26:59.880 --> 00:27:02.280] So Ozempic face is just like you lost weight face.
[00:27:02.280 --> 00:27:02.840] Yeah, totally.
[00:27:03.320 --> 00:27:08.920] These ones just strike me, as we were talking about beforehand, like these ones just strike me as so fucking mean.
[00:27:08.920 --> 00:27:12.360] It's also so fucked up because it's like our culture is telling you to lose weight all the fucking time.
[00:27:12.360 --> 00:27:14.200] And it's like you finally do lose weight.
[00:27:14.200 --> 00:27:15.640] It's like, what's happening to your face?
[00:27:15.640 --> 00:27:16.200] Yeah, totally.
[00:27:16.200 --> 00:27:25.400] Well, and people treat it as like some kind of like comeuppance for like taking a drug or daring to lose weight or being too vain or what, like whatever.
[00:27:25.400 --> 00:27:28.040] Like it's just steeped in so much judgment.
[00:27:28.040 --> 00:27:28.280] Right.
[00:27:28.280 --> 00:27:30.840] That I'm like, could we just set that one down?
[00:27:30.840 --> 00:27:35.400] There's also a bunch of like very rare side effects.
[00:27:35.400 --> 00:27:38.920] So there's been some worry about pancreatitis.
[00:27:38.920 --> 00:27:45.560] Some trials find that it like increases, but then there's a trial of the araglatide that finds that it actually decreases.
[00:27:45.560 --> 00:27:51.800] There's concern about thyroid cancer, but that's based on rodent studies.
[00:27:51.800 --> 00:27:58.520] And there haven't been any signs of that in the data, but we don't know kind of any longer than one and a half to two years.
[00:27:58.840 --> 00:28:05.480] There's slightly elevated rates of gallbladder disease, acute kidney injury.
[00:28:05.480 --> 00:28:14.360] There's two cases in Iceland of suicidal ideation, and the European Medicines Agency is now looking into that.
[00:28:14.480 --> 00:28:29.120] And just this week, the FDA updated the label on samaglatide to include this thing ileus, which is basically when like digested food builds up in your intestine and backs up.
[00:28:29.440 --> 00:28:34.000] And the only way to deal with it is surgery and it's fatal.
[00:28:34.000 --> 00:28:40.160] So we have 33 cases of this that have been reported to the adverse events database and two deaths.
[00:28:40.640 --> 00:28:49.120] But we don't sort of know what to make of those things because the adverse events database is like, as we've discussed on the show before, it's like anyone can submit cases.
[00:28:49.120 --> 00:28:50.720] So it's basically just like a hotline.
[00:28:51.040 --> 00:28:53.840] And so it's something that is like people are looking into more.
[00:28:53.840 --> 00:29:02.880] And there's a study out of China last year that shows that this mechanism exists in mice, where it like basically stops bowel function.
[00:29:02.880 --> 00:29:12.800] And there was some kind of warning in that study of like, oh, this might show up in humans and it might show up around the sort of 18-month mark, meaning like after these studies would have concluded.
[00:29:12.800 --> 00:29:16.160] But that's also like animal studies, super preliminary.
[00:29:16.160 --> 00:29:16.720] We don't know.
[00:29:16.720 --> 00:29:19.680] It's sort of like people don't really know what to make of this yet.
[00:29:19.680 --> 00:29:32.480] Yeah, and you know, two people dying is nothing to context of previous diet drugs having sort of gone this way.
[00:29:32.480 --> 00:29:32.720] Yeah.
[00:29:33.280 --> 00:29:39.040] But then one thing that really stood out to me was, you know, we have these like near universal side effects.
[00:29:39.040 --> 00:29:42.560] We have these like much more rare, much more severe side effects.
[00:29:42.560 --> 00:29:45.600] But the dropout rates in these studies are like really low.
[00:29:45.920 --> 00:29:52.000] What you find in most of the studies is almost everybody is getting some side effect or another.
[00:29:52.000 --> 00:29:56.000] And they typically happen in the first couple weeks of the study when you're like upping your dose.
[00:29:56.000 --> 00:30:04.360] It actually takes four months to get up to the 2.4 milligrams like weight loss dose, but it typically goes away as people kind of get used to the drugs.
[00:30:04.680 --> 00:30:15.000] And so, in the two-year study, there were 150 people who completed the two-year trial, and only 10 of them dropped out due to adverse effects, which is only 6%.
[00:30:15.320 --> 00:30:25.160] So, like, what this indicates is that people are getting side effects, but most, like, the vast majority of people are willing to push through the side effects and complete these trials.
[00:30:25.160 --> 00:30:33.240] Yeah, so what you're saying is folks are more likely to stay in these studies than other studies into sort of like how folks can lose weight.
[00:30:33.240 --> 00:30:33.720] Yes.
[00:30:34.040 --> 00:30:43.640] So, so far, I've kind of been presenting like the case for samaglatide, like the way that you read about it in these clinical trials.
[00:30:43.640 --> 00:30:47.720] I've been reading a lot of things from like, you know, people in like the weight loss world.
[00:30:47.720 --> 00:30:50.760] And like, this is how they talk about the drug, right?
[00:30:50.760 --> 00:30:53.640] Is that it's delivering very significant weight loss.
[00:30:53.640 --> 00:30:56.040] The dropout rates are relatively low.
[00:30:56.040 --> 00:31:04.680] And before we get to like complicating that picture a little bit, I think it's important to first of all just like acknowledge that like that is the data that we have.
[00:31:04.680 --> 00:31:08.840] And like, I think this new generation of weight loss drugs is like genuinely just a big deal.
[00:31:09.000 --> 00:31:21.240] At the same time, to me, like the most bizarre thing about the discourse, especially recently, but you know, since the results of these trials started coming out, is like the weird victory lap that people have been doing.
[00:31:21.240 --> 00:31:24.760] It's like, okay, we know we have something now that works for weight loss, right?
[00:31:24.760 --> 00:31:27.400] We finally have an effective weight loss drug.
[00:31:27.400 --> 00:31:32.600] And then there's this weird sort of second-order thing where they're like, what are the fat activists gonna do now?
[00:31:32.840 --> 00:31:34.840] Like, this ruins body positivity.
[00:31:34.840 --> 00:31:40.360] And there's all this weird shit of like, well, now we have a cure for obesity, right?
[00:31:40.360 --> 00:31:46.000] And I feel like just to sort of take these results as we've been presented with them, right?
[00:31:46.000 --> 00:31:49.920] Like the quote unquote best possible version of these events, right?
[00:31:44.680 --> 00:31:52.080] All of the weight loss, all of the benefits, everything.
[00:31:52.400 --> 00:32:03.040] It's like, we're talking about a drug that 50% of people who take it will lose 15% of their body weight.
[00:32:03.040 --> 00:32:06.000] And like, that is not a world without fat people.
[00:32:06.160 --> 00:32:09.440] This is like the aspect of the drug that drives me absolutely fucking nuts.
[00:32:09.440 --> 00:32:12.800] It's not going to end the quote unquote obesity epidemic.
[00:32:12.800 --> 00:32:13.600] It just isn't.
[00:32:14.000 --> 00:32:20.720] We still, as a society, need to work on like stigma against fat people, improving medical care for fat people.
[00:32:20.720 --> 00:32:28.640] All of the things we say on this show are still fucking true if every single person in America loses 15% of their body weight.
[00:32:28.640 --> 00:32:32.560] And that is a dramatic overestimation of what's even about to happen, right?
[00:32:32.880 --> 00:32:41.760] Even if, as you say, even if they work exactly as they are projected to, even if the data doesn't change one bit with future trials.
[00:32:41.760 --> 00:32:42.240] Yeah.
[00:32:42.240 --> 00:32:48.480] Someone my size goes from being 330 pounds to being 280 pounds.
[00:32:48.480 --> 00:32:58.240] That would take me from being a person with an obese BMI to being a person with an obese BMI.
[00:32:58.240 --> 00:32:58.720] Yeah.
[00:32:58.720 --> 00:33:03.760] This whole thing about like, you know, is this the end of the obesity epidemic?
[00:33:03.760 --> 00:33:07.440] Like, A, no, it's not, as you've pointed out.
[00:33:07.440 --> 00:33:12.080] But B, that is the meanest fucking thing to say.
[00:33:12.080 --> 00:33:19.200] We currently have this fucking nightmare bullshit, which is like the whole fucking show is dedicated to this, where it's like, a fat person goes into the doctor for a migraine, and they're like, I have a migraine.
[00:33:19.200 --> 00:33:20.600] And the doctor's like, you should go on a diet.
[00:33:20.640 --> 00:33:21.000] Yeah.
[00:33:21.120 --> 00:33:22.800] And then it's like, you haven't asked me what I do.
[00:33:22.800 --> 00:33:24.160] You haven't asked me if I eat fast food.
[00:33:24.160 --> 00:33:25.920] You haven't asked me fucking anything.
[00:33:25.920 --> 00:33:29.280] You're giving me this bullshit ass advice when all I want is fucking advice for my migraine, right?
[00:33:29.280 --> 00:33:29.520] Yeah.
[00:33:29.520 --> 00:33:32.840] We're now going into a scenario where you go into the doctor with a migraine.
[00:33:32.840 --> 00:33:34.040] They're like, you should go on Ozempic.
[00:33:34.120 --> 00:33:34.280] Yeah.
[00:33:29.840 --> 00:33:36.200] And you're like, well, I've already been on Ozempic three times.
[00:33:36.440 --> 00:33:41.320] And I was half, I was one of the half of people who lost less than 10% of my body weight.
[00:33:41.320 --> 00:33:43.480] It was costing me more than my fucking rent.
[00:33:43.480 --> 00:33:44.920] I was having weird side effects.
[00:33:44.920 --> 00:33:48.280] People report like not enjoying food anymore, which is like really sad to think about.
[00:33:48.600 --> 00:33:51.160] And then the minute I went off of it, I gained all the fucking weight back.
[00:33:51.160 --> 00:33:52.920] And I've done that four times.
[00:33:52.920 --> 00:33:56.680] And when I'm going in, you're giving me this generic bullshit fucking advice to go on Ozempic.
[00:33:56.680 --> 00:33:58.440] You haven't asked me whether I've been on it before.
[00:33:58.440 --> 00:33:59.560] You haven't asked me about weight cycling.
[00:33:59.560 --> 00:34:03.640] You haven't asked me whether I tolerate the drug or if it intersects with some like antidepressant that I'm taking.
[00:34:03.880 --> 00:34:08.520] We're just redoing the same fucking thing, except instead of go on a diet, it's go on Ozempic.
[00:34:08.520 --> 00:34:08.840] Yeah.
[00:34:08.840 --> 00:34:16.680] And like in the same way that it's not possible for everyone to go on a fucking diet or they've been on a million already, it's not possible for everyone to go on fucking Ozempic and it's not going to work for everybody.
[00:34:16.680 --> 00:34:24.840] I mean, I told, listen, I told you this off mic, but I think this is the darkest episode that I have researched for us.
[00:34:24.840 --> 00:34:25.720] Yeah, it's really bad.
[00:34:25.880 --> 00:34:28.040] It is really upsetting.
[00:34:28.040 --> 00:34:34.920] And I will say, like, not just on an individual level, but also like systemically.
[00:34:34.920 --> 00:34:38.840] Like, I stopped seeing doctors for like eight years.
[00:34:38.840 --> 00:34:41.240] I've written about this a bunch of times.
[00:34:41.240 --> 00:34:46.120] And that was at the height of like the bariatric surgery craze.
[00:34:46.120 --> 00:34:46.760] Yeah.
[00:34:46.760 --> 00:34:52.520] And that really fucking fueled how doctors would talk to me and what treatments they would offer me.
[00:34:52.520 --> 00:35:04.040] And it was like a very frequent conversation of me being like, hey, I'm 24 and I have an entry-level position at a nonprofit where I feel fortunate to have health coverage at all.
[00:35:04.040 --> 00:35:07.720] No, I don't have 25 grand for a weight loss.
[00:35:08.040 --> 00:35:08.440] Right.
[00:35:08.440 --> 00:35:08.760] Yeah.
[00:35:08.760 --> 00:35:22.560] But that still became a thing, right, amongst healthcare providers who we already know are more likely to think of fat patients as non-compliant, as slovenly, as unattractive, as weak-willed, as all of these things, right?
[00:35:22.560 --> 00:35:28.960] Like, this becomes another reason for that group of people also to stop listening to fat people.
[00:35:29.280 --> 00:35:32.400] Like, it's going to get harder for me to get health care.
[00:35:32.400 --> 00:35:33.040] Right, right.
[00:35:33.040 --> 00:35:34.640] That's part of what's about to happen.
[00:35:35.200 --> 00:35:43.360] This is why I wanted to go out of my way to like insufferably present the results of these trials as if they will hold up.
[00:35:43.680 --> 00:35:51.680] Because even in a world in which that happens, that doesn't call anything into question about the need for equal treatment.
[00:35:51.680 --> 00:35:59.120] And at the same time, the results of these trials are extremely unlikely to pan out in the real world.
[00:35:59.120 --> 00:35:59.920] Yeah, totally.
[00:35:59.920 --> 00:36:10.080] So I have three reasons why these drugs are very unlikely to pan out and deliver like the end of obesity or all the stuff that the insufferable discourse has been telling us.
[00:36:10.400 --> 00:36:12.240] We're tucking into the debunk bed.
[00:36:12.240 --> 00:36:14.880] Yeah, this is much more comfortable space for us.
[00:36:14.880 --> 00:36:21.360] The first is that the populations that are being studied in these trials are actually relatively narrow.
[00:36:21.360 --> 00:36:32.400] So step one, which is the trial that's kind of the overall, like just normal weight loss drugs being given to people, I'm going to read you the exclusion criteria.
[00:36:32.400 --> 00:36:39.200] People were not able to participate in step one if they have a history of major depressive disorder.
[00:36:39.200 --> 00:36:39.520] Okay.
[00:36:39.520 --> 00:36:43.280] They have a diagnosis of a severe psychiatric disorder.
[00:36:43.280 --> 00:36:48.960] They fill out the patient health questionnaire with a score of over 15.
[00:36:48.960 --> 00:36:55.760] This is one of those, one of those questionnaires that has, like, you know, I have feelings of hopelessness, like rank from like every day to like never.
[00:36:55.760 --> 00:36:56.160] Yeah, yeah, yeah, yeah.
[00:36:56.320 --> 00:36:58.800] It's basically a measure of like how depressed you are.
[00:36:58.800 --> 00:37:00.760] It's like, are you feeling tired?
[00:36:59.680 --> 00:37:03.880] One of them is, do you have poor appetite or overeating?
[00:37:03.880 --> 00:37:06.840] Which is like a funny exclusion criteria to include in this.
[00:37:07.000 --> 00:37:32.280] They're also excluding people with a lifetime history of a suicide attempt, any history of myocardial infarction, stroke, hospitalization, any kind of existing cardiovascular stuff, known or suspected abuse of alcohol or recreational drugs, and female who is pregnant, breastfeeding, intends to become pregnant, or is of childbearing age and not using a highly effective contraceptive method.
[00:37:32.280 --> 00:37:35.320] Holy shit, that cuts out so many people, Michael.
[00:37:35.320 --> 00:37:50.280] Well, the thing is, I mean, with these studies, like I sort of get why people who design studies do this stuff, because they want to start with a kind of baseline of like quote unquote normal people without a bunch of like pre-existing conditions, which I get for the purpose of a trial.
[00:37:50.280 --> 00:37:53.960] I get why you want to have like a clean, quote-unquote sample.
[00:37:53.960 --> 00:38:00.680] However, once these drugs get out into the real world, they're going to be taken by people with depression.
[00:38:00.680 --> 00:38:05.080] Yeah, like when you're designing a trial like this, I imagine you're walking a real line, right?
[00:38:05.080 --> 00:38:08.520] You want the trial itself to be safe for the people who participate in it.
[00:38:08.520 --> 00:38:18.440] So you want to eliminate things like existing heart conditions, like anything, existing pancreatic conditions, anything sort of related to the mechanisms involved in this drug.
[00:38:18.440 --> 00:38:19.960] I totally get that, right?
[00:38:20.360 --> 00:38:24.920] And you don't want it to make anything worse for anybody, like just on a human level.
[00:38:24.920 --> 00:38:26.760] That totally makes sense to me.
[00:38:26.760 --> 00:38:40.360] The trick is all of that gets translated into an assumption that this is how it will play out for all people who are not being monitored in a study and provided the drug for free.
[00:38:40.360 --> 00:38:40.920] Yeah.
[00:38:40.920 --> 00:38:47.760] And all people who have all of these other conditions that are extremely prevalent in the US, right?
[00:38:44.920 --> 00:38:48.000] Yes.
[00:38:48.320 --> 00:39:04.560] And also, I mean, we, I probably should have started with this, but the second reason why it's unlikely that these are going to deliver on the results that we're seeing in the trials is because there are real-world studies of samaglatide and they don't find the same results.
[00:39:04.800 --> 00:39:11.920] So there's a study in the US that followed like people who went to weight loss clinics and got these drugs for one year.
[00:39:11.920 --> 00:39:17.440] If you remember in the trials of these drugs, the average weight loss was around 15%.
[00:39:17.760 --> 00:39:21.920] In the real world trial, people are losing 7.5% of their body weight.
[00:39:21.920 --> 00:39:31.440] And there are other real-world trials, it's quite remarkable actually, that find almost the same thing that like the weight loss, you know, 80% of people lose 5% of their body weight or more.
[00:39:31.440 --> 00:39:33.840] In the real world, that tends to be around 40%.
[00:39:34.080 --> 00:39:40.480] So almost all of the numbers that we're seeing in these randomized control trials are half once we get to the real world.
[00:39:40.480 --> 00:39:41.600] They're not zero, right?
[00:39:41.600 --> 00:39:49.360] So this still is going to be, again, a big deal, but we're not seeing in the real world those results continue to show up.
[00:39:49.680 --> 00:39:53.440] It's not totally clear why this is happening.
[00:39:53.440 --> 00:40:03.440] One of them appears to be that in the randomized control trials, people aren't just taking the drug, they're also getting like dietary counseling.
[00:40:03.440 --> 00:40:09.360] So one of the trials is like super intensive behavioral therapy where they're like meeting with dietitians once a week.
[00:40:09.360 --> 00:40:17.680] But in all of the other trials, they're doing monthly check-ins with counselors and they're having all of these, you know, bio-markers taken.
[00:40:17.680 --> 00:40:21.200] And I think there's something about like people just being in a study.
[00:40:21.200 --> 00:40:23.920] Like you really want to finish because you're like, oh, I'm part of this like project.
[00:40:23.920 --> 00:40:26.240] And it's like experimental and super cool.
[00:40:26.240 --> 00:40:34.360] And like, the adherence rates for these randomized controlled trials are like significantly higher than we have in the real world.
[00:40:34.520 --> 00:40:45.720] When you look at the real world trials, even among people who have type 2 diabetes and who like really need these drugs, a lot of them are finding like 50% dropout rates after two years.
[00:40:45.720 --> 00:40:48.680] And some of them, one of them, finds 70% dropout rate.
[00:40:48.680 --> 00:41:00.280] You can already see as we're sort of like walking through this research, the gap between the popular claims that are being made about these drugs and what the research actually says.
[00:41:00.280 --> 00:41:02.440] That's where we got to with Fenfen.
[00:41:02.440 --> 00:41:03.960] That's where we got to with Ally.
[00:41:04.120 --> 00:41:16.200] That's where we got to with like, this is sort of a pattern with weight loss drugs: is that we get out over our skis culturally with like this kind of magical thinking excitement stuff.
[00:41:16.760 --> 00:41:22.600] We then make a bunch of policy decisions based on the excitement and not the data.
[00:41:22.920 --> 00:41:34.120] And then we're kind of stuck with these sort of adjusted systems that were, again, changed based on what we thought was possible, not what we were actually seeing.
[00:41:34.120 --> 00:41:34.600] Exactly.
[00:41:34.600 --> 00:41:45.400] And the other thing that, again, we have very good data on is that people tend to regain all of the weight the second they stop taking these drugs.
[00:41:45.720 --> 00:41:52.840] So one of the STEP studies switched people from somaglatide to a placebo at 20 weeks.
[00:41:52.840 --> 00:41:59.000] There's also a trial of another GLP1, Tyrzepatide, these fucking tides, that did the same thing.
[00:41:59.000 --> 00:42:01.960] After 36 weeks, they switched people to a placebo.
[00:42:01.960 --> 00:42:06.120] And basically, it's like people start regaining the weight very quickly.
[00:42:06.120 --> 00:42:09.960] And like within a year, they've regained almost all of the weight.
[00:42:10.120 --> 00:42:17.440] These drugs seem to put people in the same cycle as fad diets, but just with like more dramatic and like longer results.
[00:42:17.760 --> 00:42:24.320] Well, and the people that I have heard talk about taking these drugs are like, I'm just going to take it until I get down to X weight and then I'm going to stop.
[00:42:24.400 --> 00:42:24.880] Yeah, yeah, yeah.
[00:42:25.120 --> 00:42:25.360] Right.
[00:42:25.360 --> 00:42:28.720] And that is people's plan for how this is going to happen.
[00:42:28.720 --> 00:42:31.200] And that's not how these drugs work.
[00:42:31.520 --> 00:42:38.000] I'm seeing this discourse among like weight loss clinicians too, where they're like, well, ultimately it comes down to diet and exercise.
[00:42:38.000 --> 00:42:42.160] And so we need to get people on these drugs and then teach them the diet and exercise stuff.
[00:42:42.160 --> 00:42:45.360] And then once they know that, we can take them off the drugs.
[00:42:45.360 --> 00:42:55.680] But this trial of kerzepatide, the other drug, had people on an intensive behavioral therapy program when they went off the drug.
[00:42:55.840 --> 00:43:04.640] So people took it for a while, then they switched to a placebo while still doing like exercise and like cooking classes and all this stuff that everybody says is so fucking effective.
[00:43:04.640 --> 00:43:06.080] And they gained all the weight back.
[00:43:06.080 --> 00:43:09.520] This is another case of pump the brakes and ask a fat person.
[00:43:09.520 --> 00:43:10.080] Yeah, yeah, yeah.
[00:43:10.320 --> 00:43:11.760] Has anybody tried to teach you how to cook?
[00:43:11.760 --> 00:43:13.520] Has anybody offered you a gym membership?
[00:43:13.520 --> 00:43:16.800] Has anybody told you that your form was wrong while you were working out?
[00:43:16.800 --> 00:43:17.280] Right.
[00:43:17.280 --> 00:43:19.040] This is every day.
[00:43:19.360 --> 00:43:25.200] The reason that people think that in part is that it reinforces our existing beliefs about fat people.
[00:43:25.200 --> 00:43:25.440] Right.
[00:43:25.440 --> 00:43:25.840] Right.
[00:43:26.000 --> 00:43:33.840] Which is just that they're too lazy or they're too unintelligent or they're too uninformed to just do it for themselves.
[00:43:33.840 --> 00:43:36.160] So they need a thin person to teach them how.
[00:43:36.160 --> 00:43:38.160] This is going on my Aubrey Gordon soundboard.
[00:43:38.160 --> 00:43:38.320] Yeah.
[00:43:38.320 --> 00:43:39.120] Step back.
[00:43:39.120 --> 00:43:40.160] Ask a fat person.
[00:43:40.160 --> 00:43:43.680] I mean, genuinely, that's going to be my advice.
[00:43:43.680 --> 00:43:45.200] Like 80% of the time.
[00:43:45.200 --> 00:43:48.080] It's like, have you even talked to a fat person about this?
[00:43:48.080 --> 00:43:56.320] This is another like super fucking familiar pattern where it's like, okay, everyone should go on Atkins because low-fat diets work and then like, or low-carb diets work.
[00:43:56.320 --> 00:44:03.080] And then, of course, after like six months, everyone gains the weight, you know, and then it's like, then it's like, well, if you stayed on it, you would have kept the weight off, which is true.
[00:44:03.080 --> 00:44:03.400] Fine.
[00:44:03.400 --> 00:44:05.320] If you can stay on it, but no one can fucking stay on it.
[00:44:05.320 --> 00:44:05.560] Yeah.
[00:44:05.560 --> 00:44:05.800] Right.
[00:43:59.840 --> 00:44:09.560] We know in the real world, no one can stay on these extreme low-carb diets for very long.
[00:44:09.560 --> 00:44:12.680] So let's move forward on that basis that no one can fucking stay on them, right?
[00:44:12.680 --> 00:44:17.160] And with this, it's going to be the same thing of like, well, Ozempic does work if you can stay on it.
[00:44:17.160 --> 00:44:17.480] Yeah.
[00:44:17.480 --> 00:44:18.920] Okay, but people aren't staying on it.
[00:44:18.920 --> 00:44:22.440] We know from real world data that even when it's fucking free, people are not staying on it.
[00:44:22.440 --> 00:44:26.360] Well, and if you do stay on it, people characterize it as the easy way out.
[00:44:26.360 --> 00:44:27.800] Yeah, and then you have this bullshit.
[00:44:27.800 --> 00:44:27.960] Right?
[00:44:27.960 --> 00:44:31.320] Like Oprah was just saying the other day, like, it's the easy way out.
[00:44:31.320 --> 00:44:32.360] So I'm not going to do it.
[00:44:32.360 --> 00:44:35.800] And I'm like, Oprah, you are in your 60s.
[00:44:35.800 --> 00:44:39.960] How hard do you think you need to have appeared to have tried?
[00:44:39.960 --> 00:44:40.360] Yeah.
[00:44:40.360 --> 00:44:50.760] And then, like, listen, the discourse makes it worse because in the discourse is like a bunch of the reporting is like, we really need to tamp down on the stigma facing people who take Ozempic.
[00:44:50.760 --> 00:44:55.960] And I'm like, is that the stigma that we need to clamp down on?
[00:44:55.960 --> 00:45:01.480] What's so fucking annoying to me about this discourse, you have like successfully radicalized me on this in like the last 72 hours.
[00:45:01.640 --> 00:45:06.120] Oh, hey, as I've been reading this, it's like this shows up everywhere.
[00:45:06.120 --> 00:45:08.360] Like, what about the stigma of taking the drugs?
[00:45:08.360 --> 00:45:12.360] But the stigma of taking Ozempic is fat phobia.
[00:45:12.360 --> 00:45:18.920] It's the same fucking stigma that fat people are facing, but just like, oh, you're taking the easy way out by using a weight loss drug.
[00:45:18.920 --> 00:45:21.800] That's the connection between fatness and virtue.
[00:45:21.800 --> 00:45:24.120] You should lose weight in the virtuous way.
[00:45:24.120 --> 00:45:25.080] Take the stairs.
[00:45:25.080 --> 00:45:26.360] Yeah, take the fucking stairs.
[00:45:26.360 --> 00:45:29.880] It's like, well, you might look thin, but you're really a fat person.
[00:45:30.280 --> 00:45:42.760] You cannot muster any fucking gumption from anybody to like give a shit about stigma against fat people, but they're super chill to invoke fat phobia against people who stop being fat.
[00:45:42.760 --> 00:45:45.040] And they still do the fucking stigma against fat people.
[00:45:44.840 --> 00:45:45.600] And they still do it.
[00:45:45.760 --> 00:45:58.800] It's also been fascinating, I'll say, on the discourse end, that like there have been all of these bizarre hand-wringing pieces from thin people being like, was body positivity for nothing?
[00:45:58.800 --> 00:46:00.400] I know, it was all a lie.
[00:46:00.400 --> 00:46:06.080] The vast majority of fat people were under no illusions about broader social acceptance.
[00:46:06.480 --> 00:46:12.000] At best, people said fewer unwanted things about our bodies.
[00:46:12.000 --> 00:46:13.440] It never stopped.
[00:46:13.440 --> 00:46:15.200] We were never lifted up.
[00:46:15.200 --> 00:46:16.720] We were never centered.
[00:46:16.720 --> 00:46:19.440] We got one lizzo out of it, right?
[00:46:20.080 --> 00:46:21.680] And we don't even have that anymore.
[00:46:21.680 --> 00:46:23.600] And we don't even have that anymore.
[00:46:23.600 --> 00:46:24.720] Like, right?
[00:46:24.720 --> 00:46:33.600] Like, the degree to which this discourse is thin people telling themselves stories that they want to hear.
[00:46:33.600 --> 00:46:40.800] It's funny to me that, like, we like meticulously outline this and planned it out, but neither one of us can resist talking about the discourse.
[00:46:41.280 --> 00:46:42.560] I hate it so much.
[00:46:42.960 --> 00:46:45.600] Like fast-forwarding to hate.
[00:46:46.240 --> 00:46:47.520] Okay, Michael.
[00:46:47.520 --> 00:46:49.200] We've talked about the drug.
[00:46:49.200 --> 00:46:52.960] Let's talk about the manufacturer of the drug.
[00:46:53.120 --> 00:46:53.440] Yeah.
[00:46:53.440 --> 00:46:57.040] Ozempic and Wegovi are both made by Novo Nordisk.
[00:46:57.040 --> 00:46:59.760] It's a big pharmaceutical company from Denmark.
[00:46:59.760 --> 00:47:00.960] From Denmark.
[00:47:00.960 --> 00:47:07.200] And their marketing practices have really set the template for all the discourse we've been seeing since.
[00:47:07.200 --> 00:47:07.520] Okay.
[00:47:07.520 --> 00:47:10.320] Wait, are there ads for Wagovi and Ozempic?
[00:47:10.320 --> 00:47:13.440] You haven't seen the O-O-O-Ozempic?
[00:47:13.440 --> 00:47:15.760] That's like the cover songs that are in all the fucking trailers now.
[00:47:15.760 --> 00:47:20.000] The very slow, brooding cover of like, I whip my hair back and forth.
[00:47:23.200 --> 00:47:27.200] I'm blue, badoo, dee dadu die, but it's like super dark.
[00:47:27.200 --> 00:47:28.160] Yeah.
[00:47:28.800 --> 00:47:34.520] No, as we've discussed many times, we're on very different, like, Instagram experiences and like algorithms.
[00:47:34.600 --> 00:47:38.120] And like, I've never seen an ad for weight loss anything.
[00:47:38.120 --> 00:47:44.440] I'll tell you what, Mike, I might give you homework at one point and be like, go watch a half an hour of TV and tell me what you notice about the ad.
[00:47:44.600 --> 00:47:45.640] Dude, no.
[00:47:47.560 --> 00:47:48.920] Absolutely not.
[00:47:48.920 --> 00:47:53.160] I watch terrestrial TV like once a fucking year when I'm like visiting my grandma.
[00:47:53.160 --> 00:47:56.120] And I'm like, this is like, this is like actively making me stupider.
[00:47:56.120 --> 00:47:58.040] It's like shocking how bad it is.
[00:47:58.040 --> 00:48:02.280] So we're going to talk a little bit about the marketing practices at Novo Nordisk.
[00:48:02.280 --> 00:48:02.600] Okay.
[00:48:02.600 --> 00:48:05.960] There is a lot here that leaves me feeling icky.
[00:48:06.120 --> 00:48:11.400] A very good example of this is a campaign called It's Bigger Than Me.
[00:48:11.400 --> 00:48:12.920] Have you seen this campaign at all?
[00:48:12.920 --> 00:48:14.280] Is it like billboards?
[00:48:14.280 --> 00:48:18.760] There are ads, there are billboards, there are branded segments on TV shows.
[00:48:18.760 --> 00:48:20.360] There are so many things.
[00:48:20.360 --> 00:48:23.720] The slogan is obesity, it's bigger than me.
[00:48:24.520 --> 00:48:35.320] The idea behind the campaign is: it's not your fault you're fat, followed immediately by it's because you have a disease and that disease requires medical treatment.
[00:48:35.560 --> 00:48:38.680] And that medical treatment can only be provided by one company.
[00:48:38.680 --> 00:48:41.400] It's bigger than me, it's $15,000 per year.
[00:48:41.400 --> 00:48:42.040] Yeah, that's right.
[00:48:42.040 --> 00:48:43.000] That's right.
[00:48:43.320 --> 00:48:52.760] As part of this campaign, Novo Nordisk has specifically courted black public figures and particularly black women as spokespeople.
[00:48:52.760 --> 00:48:55.640] Their first spokesperson was Queen Latifah.
[00:48:55.640 --> 00:48:59.880] Their next was Yvette Nicole Brown, who was on Community.
[00:49:00.520 --> 00:49:14.360] Their third was Roland Martin from CNN, who ran an hour-long segment on fatness in black communities that was listed as quote-unquote powered by Novo Nordisk.
[00:49:14.360 --> 00:49:18.480] That's like when influencers say, like, I've partnered with Nike or whatever.
[00:49:14.840 --> 00:49:20.960] It's like, it's just them paying you to say words.
[00:49:21.280 --> 00:49:36.480] Well, and on top of that, the reporting around the quote-unquote, it's bigger than me campaign is just rife with like the most garbage messages about fatness and body positivity and all kinds of stuff.
[00:49:36.480 --> 00:49:41.600] So I read an interview with Yvette Nicole Brown with the Grio.
[00:49:41.600 --> 00:49:47.840] In that interview, she said, quote, being focused on your health does not mean that you're not body positive.
[00:49:47.840 --> 00:49:54.480] I think it's actually the most exemplary way that you can be body positive because you need your body to continue to live.
[00:49:54.480 --> 00:49:57.200] Aubrey, were you just like losing your mind?
[00:49:57.200 --> 00:50:00.160] You hate this body positivity stuff already.
[00:50:00.480 --> 00:50:09.520] This is like, this is reifying everything you've said about the whole body positivity thing that it's all just like they're repackaging the same shit and selling it back to you.
[00:50:09.520 --> 00:50:20.160] The article goes on to say that, quote, Brown said somewhere down the line, society at large developed the idea that if you're body positive, you can't care about physical health.
[00:50:20.800 --> 00:50:25.200] In my notes, I wrote, in all caps, who is saying this?
[00:50:25.200 --> 00:50:26.480] Who fucking said this?
[00:50:27.040 --> 00:50:27.760] Who is saying this?
[00:50:27.760 --> 00:50:29.360] And it's like trolls, right?
[00:50:29.360 --> 00:50:35.840] It's like it's seeding a bad faith argument to be like, we don't think that's true.
[00:50:35.840 --> 00:50:38.320] Look at what all those nutty people are saying.
[00:50:38.320 --> 00:50:39.280] They're wrong.
[00:50:39.280 --> 00:50:44.320] This is like when conservatives are like, feminists don't even want you to get married and have kids.
[00:50:44.320 --> 00:50:48.240] It's the phenomenon that has built Michael Hobbes' Twitter feed.
[00:50:48.240 --> 00:50:49.280] Hey.
[00:50:49.280 --> 00:50:49.680] Hey.
[00:50:50.320 --> 00:50:52.320] You're familiar with my work.
[00:50:52.640 --> 00:51:02.760] So, our third section, Michael, is the part that I have realized is most troubling to me, and that is the discourse.
[00:50:59.920 --> 00:51:06.520] There's been a lot of like garbage media about this in the last like year.
[00:51:06.840 --> 00:51:11.640] Here are three actual fucking headlines from coverage of this.
[00:51:12.200 --> 00:51:17.400] One, will Ozempic change how we think of being fat and thin?
[00:51:17.400 --> 00:51:18.360] Question mark.
[00:51:18.360 --> 00:51:18.920] Okay.
[00:51:18.920 --> 00:51:20.520] Life after food?
[00:51:20.520 --> 00:51:21.400] Question mark?
[00:51:22.040 --> 00:51:25.960] And Ozempic settles the obesity debate.
[00:51:25.960 --> 00:51:26.520] Oh.
[00:51:27.320 --> 00:51:34.760] It is just bad faith proclamations and bullshit question mark headlines, like as far as the eye can see.
[00:51:34.760 --> 00:51:35.000] Yeah.
[00:51:35.400 --> 00:51:47.240] What I am worried about is that when we see a wave of media like we have seen around Ozempic, we also tend to see a wave of increased anti-fat bias, right?
[00:51:47.240 --> 00:51:47.560] Right.
[00:51:47.560 --> 00:51:47.960] Right.
[00:51:47.960 --> 00:51:55.080] And the reporting that I have seen so far, the think pieces that I have seen so far, none of them are grappling with that.
[00:51:55.080 --> 00:51:55.640] Right.
[00:51:55.640 --> 00:52:04.760] Very few people are asking fat people what they need in this moment, and nobody is asking diabetic people what they need in this moment.
[00:52:04.760 --> 00:52:20.040] Like a thing that I experientially know in every bone in my body is that when people I know start to lose weight, the vast majority of them start to see themselves as more virtuous.
[00:52:20.040 --> 00:52:20.520] Yeah.
[00:52:20.520 --> 00:52:26.360] Whether they want to or not, whether they mean to or not, whether or not they would say it out loud.
[00:52:26.360 --> 00:52:26.760] Yeah.
[00:52:26.760 --> 00:52:31.080] It's very common for people to expect social reinforcement for weight loss.
[00:52:31.400 --> 00:52:40.280] And I would say now, as I have said for years now, which is you have got to get people's consent to do that.
[00:52:40.600 --> 00:52:45.000] The best case scenario is that you're sending a message that you're like not a very good friend to a fat person.
[00:52:45.680 --> 00:52:46.160] Right.
[00:52:47.040 --> 00:52:53.840] And the worst case scenario is that you're increasing the stigma that they face and potentially also like triggering people's eating disorders.
[00:52:53.840 --> 00:52:54.240] Yeah.
[00:52:54.240 --> 00:52:57.040] Like this shit is not unthorny.
[00:52:57.040 --> 00:53:00.960] And the fact that you're hearing it everywhere doesn't make it less urgent.
[00:53:00.960 --> 00:53:05.120] I would argue it makes it more urgent to like double up on those boundaries.
[00:53:05.120 --> 00:53:09.440] Like you have got to give fat people an out for this conversation.
[00:53:09.440 --> 00:53:15.760] And we've got to stop presuming that this is like a good and exciting conversation for everybody.
[00:53:15.760 --> 00:53:19.680] I'm like not all that invested in like the drugs themselves.
[00:53:19.680 --> 00:53:20.560] The drugs are the drugs.
[00:53:21.120 --> 00:53:21.520] I don't know.
[00:53:21.520 --> 00:53:22.400] I mean, same, same.
[00:53:22.560 --> 00:53:24.160] Maybe they'll be effective weight loss drugs.
[00:53:24.160 --> 00:53:24.960] Maybe they won't.
[00:53:24.960 --> 00:53:25.760] I don't know.
[00:53:25.760 --> 00:53:35.120] But like, given what we know now, the most likely scenario is that like they're going to be prescribed to millions, potentially tens of millions of people.
[00:53:35.120 --> 00:53:47.680] And like what you said to me the other day is that like you can see the number of people who lost like 15 fucking pounds and then all of a sudden are like really mean to fat people, just like exponentially increasing.
[00:53:47.680 --> 00:54:06.960] The other thing that I will say about the discourse around this is that every like celebratory story about Ozempic that comes out now, that's all going to be mirrored by future panicky think pieces on the rising costs of obesity and how fat people are bankrupting us once again, right?
[00:54:07.040 --> 00:54:16.240] This is an unbelievably expensive medication and all of that is going to come back to scapegoating fat people once again, right?
[00:54:16.240 --> 00:54:20.240] That like right now we're saying it's frivolous housewives and whatever.
[00:54:20.240 --> 00:54:24.320] When we get into the insurance conversations, we're not going to be scapegoating rich people.
[00:54:24.320 --> 00:54:25.920] We generally don't do that.
[00:54:25.920 --> 00:54:29.760] We scapegoat poor people, BIPOC, fat people, queer people.
[00:54:29.960 --> 00:54:30.520] You know what I mean?
[00:54:30.520 --> 00:54:32.520] Like, we've got a list of people we scapegoat.
[00:54:32.520 --> 00:54:40.440] We're also setting ourselves up for another round of excruciating discourse in another couple years when people look around and they're like, wait a minute, there's still fat people.
[00:54:40.440 --> 00:54:40.760] Yeah.
[00:54:40.760 --> 00:54:47.560] All the magazines told me a couple of years ago that this was the end of obesity, and yet people are still fat.
[00:54:47.560 --> 00:54:54.520] We should also say, listen, you will face serious, serious fucking stigma as a person who stays fat.
[00:54:55.080 --> 00:54:59.560] Trust me, a person who has stayed fat through all the interventions, right?
[00:54:59.560 --> 00:55:04.920] Like, I've already sort of started shifting socially.
[00:55:04.920 --> 00:55:20.040] You know, I'm already a very homebody, indoorsy kind of lady, and I'm already restricting who I socialize with pretty dramatically because of this kind of talk and because I'm unwilling to be in spaces where this shit will come up.
[00:55:20.040 --> 00:55:20.440] Yeah.
[00:55:20.440 --> 00:55:20.680] Right.
[00:55:21.000 --> 00:55:27.960] And for me, that means functionally, like a vast majority of people I know who are not fat and some people I know who are.
[00:55:27.960 --> 00:55:28.280] Right.
[00:55:28.280 --> 00:55:28.440] Right.
[00:55:28.440 --> 00:55:35.560] So like, I just want people to understand, like, the stakes of this as a fat person are: I feel like I don't belong in the world.
[00:55:35.560 --> 00:55:35.960] Right.
[00:55:35.960 --> 00:55:41.560] When people talk about how great it's going to be when I'm not around, it's that's not me being too sensitive.
[00:55:41.560 --> 00:55:43.480] That's not fat people taking it too hard.
[00:55:43.480 --> 00:55:45.640] That's you saying plainly, right?
[00:55:45.640 --> 00:55:47.480] Everything will be better when you're gone.
[00:55:47.480 --> 00:55:47.800] Right.
[00:55:48.120 --> 00:55:50.520] And then fat people like taking that message.
[00:55:50.520 --> 00:55:52.280] That's horrible.
[00:55:52.440 --> 00:55:56.520] The fact that you have been through so many rounds of this, it's like, why aren't you on Fenfin?
[00:55:56.600 --> 00:55:58.360] Why aren't you on bariantrosurger?
[00:55:58.360 --> 00:55:59.320] Why aren't you clean eating?
[00:55:59.320 --> 00:56:04.520] Why aren't like all this is just new packaging for like, why aren't you thin?
[00:56:04.520 --> 00:56:04.920] Yeah.
[00:56:04.920 --> 00:56:06.840] And like, that is worth listening to.
[00:56:06.840 --> 00:56:10.280] This isn't like a paranoid fantasy on the part of fat people.
[00:56:10.280 --> 00:56:14.440] This is something that they've been through numerous times over the course of their lifetimes now.
[00:56:15.600 --> 00:56:22.480] We're just doing the same thing again, even when the data does not remotely indicate that we're not going to have fat people anymore.
[00:56:22.480 --> 00:56:23.120] It never has.
[00:56:23.120 --> 00:56:24.480] We're always going to have fat people.
[00:56:24.480 --> 00:56:32.240] And there's always going to be people, whatever the medical intervention is, that can't use it or it doesn't work for them or they've tried it already.
[00:56:32.240 --> 00:56:34.320] That's always going to be the case.
[00:56:34.320 --> 00:56:34.720] Yeah.
[00:56:34.960 --> 00:56:39.920] The fact that people are so obsessed with asking the question, is what's the end of obesity?
[00:56:39.920 --> 00:56:40.720] Like really early.
[00:56:40.720 --> 00:56:41.040] Yeah.
[00:56:41.040 --> 00:56:44.160] Like, oh, is this going to be the reason we don't have fat people around anymore?
[00:56:44.160 --> 00:56:46.080] It's like, it's so fucking telling.
[00:56:46.080 --> 00:56:50.080] So moving forward, we're going to continue to get these drugs.
[00:56:50.080 --> 00:56:53.840] We're going to continue to get this sort of quote-unquote gold rush.
[00:56:53.840 --> 00:57:07.760] And in that time, I think it is worth being extra skeptical and returning to the voices of fat people and diabetic people when media isn't doing that for us, right?
[00:57:08.080 --> 00:57:27.520] To like actually return to the people who are most impacted by this debate and to spend way the fuck less time speculating about Elon Musk and Courtney Kardashian and making celebrities defend themselves and like trying to think through how do we get these drugs to peop

Prompt 2: Key Takeaways

Now please extract the key takeaways from the transcript content I provided.

Extract the most important key takeaways from this part of the conversation. Use a single sentence statement (the key takeaway) rather than milquetoast descriptions like "the hosts discuss...". 

Limit the key takeaways to a maximum of 3. The key takeaways should be insightful and knowledge-additive. 

IMPORTANT: Return ONLY valid JSON, no explanations or markdown. Ensure:
- All strings are properly quoted and escaped
- No trailing commas
- All braces and brackets are balanced
Format: {"key_takeaways": ["takeaway 1", "takeaway 2"]}

Prompt 3: Segments

Now identify 2-4 distinct topical segments from this part of the conversation.

For each segment, identify:
- Descriptive title (3-6 words)  
- START timestamp when this topic begins (HH:MM:SS format)
- Double check that the timestamp is accurate - a timestamp will NEVER be greater than the total length of the audio
- Most important Key takeaway from that segment. Key takeaway must be specific and knowledge-additive.
- Brief summary of the discussion

IMPORTANT: The timestamp should mark when the topic/segment STARTS, not a range. Look for topic transitions and conversation shifts.

Return ONLY valid JSON. Ensure all strings are properly quoted, no trailing commas:
{
  "segments": [
    {
      "segment_title": "Topic Discussion", 
      "timestamp": "01:15:30",
      "key_takeaway": "main point from this segment",
      "segment_summary": "brief description of what was discussed"
    }
  ]
}

Timestamp format: HH:MM:SS (e.g., 00:05:30, 01:22:45) marking the START of each segment.

Prompt 4: Media Mentions

Now scan the transcript content I provided for ACTUAL mentions of specific media titles:

Find explicit mentions of:
- Books (with specific titles)
- Movies (with specific titles)  
- TV Shows (with specific titles)
- Music/Songs (with specific titles)

DO NOT include:
- Websites, URLs, or web services
- Other podcasts or podcast names

IMPORTANT: 
- Only include items explicitly mentioned by name. Do not invent titles.
- Valid categories are: "Book", "Movie", "TV Show", "Music"
- Include the exact phrase where each item was mentioned
- Find the nearest proximate timestamp where it appears in the conversation
- THE TIMESTAMP OF THE MEDIA MENTION IS IMPORTANT - DO NOT INVENT TIMESTAMPS AND DO NOT MISATTRIBUTE TIMESTAMPS
- Double check that the timestamp is accurate - a timestamp will NEVER be greater than the total length of the audio
- Timestamps are given as ranges, e.g. 01:13:42.520 --> 01:13:46.720. Use the EARLIER of the 2 timestamps in the range.

Return ONLY valid JSON. Ensure all strings are properly quoted and escaped, no trailing commas:
{
  "media_mentions": [
    {
      "title": "Exact Title as Mentioned",
      "category": "Book",
      "author_artist": "N/A",
      "context": "Brief context of why it was mentioned",
      "context_phrase": "The exact sentence or phrase where it was mentioned",
      "timestamp": "estimated time like 01:15:30"
    }
  ]
}

If no media is mentioned, return: {"media_mentions": []}

Prompt 5: Context Setup

You are an expert data extractor tasked with analyzing a podcast transcript. 
I will provide you with part 2 of 2 from a podcast transcript. 
I will then ask you to extract different types of information from this content in subsequent messages. Please confirm you have received and understood the transcript content.

Transcript section:
n?
[00:56:04.520 --> 00:56:04.920] Yeah.
[00:56:04.920 --> 00:56:06.840] And like, that is worth listening to.
[00:56:06.840 --> 00:56:10.280] This isn't like a paranoid fantasy on the part of fat people.
[00:56:10.280 --> 00:56:14.440] This is something that they've been through numerous times over the course of their lifetimes now.
[00:56:15.600 --> 00:56:22.480] We're just doing the same thing again, even when the data does not remotely indicate that we're not going to have fat people anymore.
[00:56:22.480 --> 00:56:23.120] It never has.
[00:56:23.120 --> 00:56:24.480] We're always going to have fat people.
[00:56:24.480 --> 00:56:32.240] And there's always going to be people, whatever the medical intervention is, that can't use it or it doesn't work for them or they've tried it already.
[00:56:32.240 --> 00:56:34.320] That's always going to be the case.
[00:56:34.320 --> 00:56:34.720] Yeah.
[00:56:34.960 --> 00:56:39.920] The fact that people are so obsessed with asking the question, is what's the end of obesity?
[00:56:39.920 --> 00:56:40.720] Like really early.
[00:56:40.720 --> 00:56:41.040] Yeah.
[00:56:41.040 --> 00:56:44.160] Like, oh, is this going to be the reason we don't have fat people around anymore?
[00:56:44.160 --> 00:56:46.080] It's like, it's so fucking telling.
[00:56:46.080 --> 00:56:50.080] So moving forward, we're going to continue to get these drugs.
[00:56:50.080 --> 00:56:53.840] We're going to continue to get this sort of quote-unquote gold rush.
[00:56:53.840 --> 00:57:07.760] And in that time, I think it is worth being extra skeptical and returning to the voices of fat people and diabetic people when media isn't doing that for us, right?
[00:57:08.080 --> 00:57:27.520] To like actually return to the people who are most impacted by this debate and to spend way the fuck less time speculating about Elon Musk and Courtney Kardashian and making celebrities defend themselves and like trying to think through how do we get these drugs to people who need them?
[00:57:27.520 --> 00:57:36.240] How do we design a better discourse that isn't so wildly dehumanizing to fat people and again to diabetic people, right?
[00:57:36.560 --> 00:57:48.640] And like, how do we just show up for people a little bit more around this stuff and interrupt some of this like dancing in the street kind of energy that is like really upsetting to see as a fat person?
[00:57:48.960 --> 00:57:50.640] Okay, we've done enough table setting.
[00:57:50.800 --> 00:57:52.080] Let's start the rest.
[00:57:53.560 --> 00:57:55.080] It's been two hours and 45 minutes.
[00:57:56.360 --> 00:57:57.240] We're ready.
[00:57:55.120 --> 00:57:58.520] We can dive in.

Prompt 6: Key Takeaways

Now please extract the key takeaways from the transcript content I provided.

Extract the most important key takeaways from this part of the conversation. Use a single sentence statement (the key takeaway) rather than milquetoast descriptions like "the hosts discuss...". 

Limit the key takeaways to a maximum of 3. The key takeaways should be insightful and knowledge-additive. 

IMPORTANT: Return ONLY valid JSON, no explanations or markdown. Ensure:
- All strings are properly quoted and escaped
- No trailing commas
- All braces and brackets are balanced
Format: {"key_takeaways": ["takeaway 1", "takeaway 2"]}

Prompt 7: Segments

Now identify 2-4 distinct topical segments from this part of the conversation.

For each segment, identify:
- Descriptive title (3-6 words)  
- START timestamp when this topic begins (HH:MM:SS format)
- Double check that the timestamp is accurate - a timestamp will NEVER be greater than the total length of the audio
- Most important Key takeaway from that segment. Key takeaway must be specific and knowledge-additive.
- Brief summary of the discussion

IMPORTANT: The timestamp should mark when the topic/segment STARTS, not a range. Look for topic transitions and conversation shifts.

Return ONLY valid JSON. Ensure all strings are properly quoted, no trailing commas:
{
  "segments": [
    {
      "segment_title": "Topic Discussion", 
      "timestamp": "01:15:30",
      "key_takeaway": "main point from this segment",
      "segment_summary": "brief description of what was discussed"
    }
  ]
}

Timestamp format: HH:MM:SS (e.g., 00:05:30, 01:22:45) marking the START of each segment.

Prompt 8: Media Mentions

Now scan the transcript content I provided for ACTUAL mentions of specific media titles:

Find explicit mentions of:
- Books (with specific titles)
- Movies (with specific titles)  
- TV Shows (with specific titles)
- Music/Songs (with specific titles)

DO NOT include:
- Websites, URLs, or web services
- Other podcasts or podcast names

IMPORTANT: 
- Only include items explicitly mentioned by name. Do not invent titles.
- Valid categories are: "Book", "Movie", "TV Show", "Music"
- Include the exact phrase where each item was mentioned
- Find the nearest proximate timestamp where it appears in the conversation
- THE TIMESTAMP OF THE MEDIA MENTION IS IMPORTANT - DO NOT INVENT TIMESTAMPS AND DO NOT MISATTRIBUTE TIMESTAMPS
- Double check that the timestamp is accurate - a timestamp will NEVER be greater than the total length of the audio
- Timestamps are given as ranges, e.g. 01:13:42.520 --> 01:13:46.720. Use the EARLIER of the 2 timestamps in the range.

Return ONLY valid JSON. Ensure all strings are properly quoted and escaped, no trailing commas:
{
  "media_mentions": [
    {
      "title": "Exact Title as Mentioned",
      "category": "Book",
      "author_artist": "N/A",
      "context": "Brief context of why it was mentioned",
      "context_phrase": "The exact sentence or phrase where it was mentioned",
      "timestamp": "estimated time like 01:15:30"
    }
  ]
}

If no media is mentioned, return: {"media_mentions": []}

Full Transcript

[00:00:00.160 --> 00:00:02.960] Wait, have I ever told you about steakhouse or gay bar?
[00:00:03.280 --> 00:00:04.240] Hang on.
[00:00:04.240 --> 00:00:06.160] I want to look it up just because it's yep.
[00:00:06.160 --> 00:00:06.480] Is it?
[00:00:06.480 --> 00:00:07.040] There we go.
[00:00:07.040 --> 00:00:07.760] What does it have?
[00:00:07.760 --> 00:00:09.360] Uh, magic castle.
[00:00:09.360 --> 00:00:10.720] Oh, it's gotta be steakhouse.
[00:00:10.720 --> 00:00:11.680] Yeah, correct.
[00:00:12.000 --> 00:00:13.600] Stockyards.
[00:00:13.600 --> 00:00:14.800] Oh, that's a gay bar.
[00:00:14.800 --> 00:00:16.480] Incorrect steakhouse.
[00:00:16.480 --> 00:00:16.960] What?
[00:00:17.280 --> 00:00:19.120] Excelsior.
[00:00:19.120 --> 00:00:21.440] That's either a bad steakhouse or a bad gay bar.
[00:00:21.440 --> 00:00:22.320] Oh, gay bar.
[00:00:22.320 --> 00:00:22.960] Fuck yes.
[00:00:22.960 --> 00:00:24.160] Oh, juicy Lucy's.
[00:00:24.160 --> 00:00:24.960] That's a steakhouse.
[00:00:24.960 --> 00:00:26.400] Sick cock in my asshole.
[00:00:26.400 --> 00:00:27.600] Oh, steakhouse.
[00:00:27.920 --> 00:00:28.320] Wow.
[00:00:28.320 --> 00:00:29.840] Charlie Brown's.
[00:00:30.160 --> 00:00:31.360] I'm not touching that.
[00:00:31.360 --> 00:00:32.320] I'm not touching that.
[00:00:32.320 --> 00:00:33.680] Let's move on.
[00:00:34.000 --> 00:00:35.040] It was a steakhouse.
[00:00:35.040 --> 00:00:36.720] Aubrey, why can't we do a fun episode?
[00:00:36.720 --> 00:00:39.760] Why can't we just do this for an hour instead of talking about Ozempic?
[00:00:50.800 --> 00:00:57.200] Welcome to Maintenance Phase, the podcast that works in the short term, but has never been tested for more than two years.
[00:00:58.800 --> 00:01:00.480] That's kind of true, actually.
[00:01:00.480 --> 00:01:01.120] Accidentally.
[00:01:01.360 --> 00:01:04.880] That is a pretty accurate thing to say about our podcast.
[00:01:04.880 --> 00:01:06.960] It hasn't been tested in long term.
[00:01:06.960 --> 00:01:08.560] People go back to where they were.
[00:01:09.120 --> 00:01:10.240] I'm Michael Hobbs.
[00:01:10.240 --> 00:01:11.520] I'm Aubrey Gordon.
[00:01:11.520 --> 00:01:18.080] If you would like to support the show, you can do that at patreon.com/slash maintenance phase, or you can subscribe on Apple Podcasts.
[00:01:18.080 --> 00:01:20.160] It's the same audio content.
[00:01:20.160 --> 00:01:21.040] Michael.
[00:01:21.040 --> 00:01:23.760] Aubrey, let's start with your nervousness.
[00:01:24.240 --> 00:01:25.440] My nervousness.
[00:01:25.440 --> 00:01:26.560] We're going to talk about it.
[00:01:26.560 --> 00:01:28.400] Your complicated feelings.
[00:01:28.400 --> 00:01:36.560] So today, we are talking about Ozempic Wegovi and their active ingredient, semaglotide.
[00:01:36.560 --> 00:01:38.160] Wait, I thought it was semaglutide.
[00:01:38.160 --> 00:01:42.480] I thought it was two, and then I heard a million doctors say semaglotide.
[00:01:42.480 --> 00:01:43.920] Semaglatide?
[00:01:43.920 --> 00:01:45.600] Doesn't that seem wrong?
[00:01:45.600 --> 00:01:46.320] Yeah, but sure.
[00:01:46.320 --> 00:01:49.760] I mean, they're made up words anyway, and then on some level, every word is made up, so whatever.
[00:01:49.760 --> 00:01:51.360] Well, listen, from Mr.
[00:01:51.360 --> 00:01:52.720] Denaumant.
[00:01:54.960 --> 00:01:58.880] It's a safe space for creative pronunciation.
[00:01:58.880 --> 00:02:04.360] The thing is, so much of the fucking feedback to this show is about my pronunciations of words.
[00:02:04.600 --> 00:02:08.280] No one ever wants to give me feedback on the content of the show.
[00:02:10.200 --> 00:02:11.320] Michael.
[00:02:12.200 --> 00:02:15.160] This episode is actually a little different than how we usually do things.
[00:02:15.160 --> 00:02:15.640] Yes.
[00:02:15.800 --> 00:02:19.640] I'm going to walk us through the drug and its origins.
[00:02:19.640 --> 00:02:26.600] You're going to walk us through the clinical trials into this sort of class of drugs.
[00:02:26.920 --> 00:02:34.040] And then we're going to talk about what I think is the thorniest part of all of this, the discourse around those drugs.
[00:02:34.040 --> 00:02:35.480] The discourse.
[00:02:35.480 --> 00:02:37.160] This is a big one.
[00:02:37.480 --> 00:02:40.360] It feels like a really high-stakes conversation.
[00:02:40.360 --> 00:02:47.240] So I'm curious about, for you, what are some of the things that you're sort of like bringing to that?
[00:02:47.240 --> 00:03:03.720] I think my weirdness with this episode is the culmination of my weirdness with every episode of the show, where both of us are interested in public health, in the kinds of things that are prescribed, how drugs get approved, what they mean societally.
[00:03:03.720 --> 00:03:21.160] Whereas because Americans have been trained by health media for our entire lives to see everything through an individualistic lens, we are going to be spending basically this entire episode talking about the narratives around Ozempic and Wagovi.
[00:03:21.160 --> 00:03:30.360] We have this new generation of weight loss drugs that as of now appear to deliver much more weight loss than any previous generation of weight loss drugs.
[00:03:30.360 --> 00:03:37.240] And we've had this immediate, huge wave of media being like, is this the end of obesity?
[00:03:37.240 --> 00:03:40.040] Does this invalidate body positivity?
[00:03:40.040 --> 00:03:50.160] And like being a dietitian in the age of Ozempic and all this just insufferable kind of endpoint prediction stuff based on very little information.
[00:03:50.480 --> 00:04:02.320] And what we are interested in and like what we have been talking about behind the scenes nonstop for the last like couple months is like how poisonous these narratives are.
[00:04:02.320 --> 00:04:06.080] But what people tend to hear is like individual health advice.
[00:04:06.080 --> 00:04:10.320] Mike and Aubrey think you shouldn't take Ozempic or Mike and Aubrey think you should take Ozempic.
[00:04:10.720 --> 00:04:13.920] And like that is just not something that we are interested in.
[00:04:13.920 --> 00:04:20.400] We've said on the show before that if you want to lose weight and you want to do keto or a cleanse, you can do that.
[00:04:20.800 --> 00:04:22.240] We don't have opinions on that.
[00:04:22.240 --> 00:04:22.800] Yeah, totally.
[00:04:22.800 --> 00:04:28.160] And if people don't want to do that, they also shouldn't be pressured to do so.
[00:04:28.160 --> 00:04:32.800] And I just know that this is like a big topic for a lot of people, right?
[00:04:32.800 --> 00:04:42.400] For me included, both because I'm engaging with all of this media and fat people writ large are engaging with all this media that is like, could we finally be rid of fat people?
[00:04:42.400 --> 00:04:46.640] Is like the framing of a lot of this conversation.
[00:04:46.640 --> 00:04:57.440] But like on top of that, I mean, we've talked about this before on the show that one of my very best friends was diabetic and passed away because she couldn't access treatment.
[00:04:57.440 --> 00:04:58.080] Yeah.
[00:04:58.080 --> 00:04:58.560] Right.
[00:04:58.560 --> 00:05:00.880] That was like facilitated by a lot of things.
[00:05:00.880 --> 00:05:06.080] It was facilitated by capitalism and anti-blackness and transphobia and lots of things.
[00:05:06.080 --> 00:05:17.040] But it was also facilitated by our sort of cultural disregard and disdain for people who have diabetes or any health conditions that we deem as quote unquote doing it to yourself.
[00:05:17.040 --> 00:05:21.680] For many folks, this is like a matter of body image, which is really tender and personal.
[00:05:21.680 --> 00:05:28.400] For other folks, for people who are on this medication for their diabetes, this can very literally be a matter of life and death.
[00:05:28.400 --> 00:05:28.800] Right.
[00:05:28.800 --> 00:05:29.280] Right.
[00:05:29.280 --> 00:07:02.640] We're talking about like a wide range of big feelings and it's like understandable right this is one of the most intense and sort of widespread moments of body related discourse we've had in quite some time right people who are taking this for weight loss are told that they're sort of taking the easy way out which they absolutely are not and which also presumes that people are fat because they don't try hard enough right right and when those people are fat they're often being forced into this kind of weight loss in order to access healthcare treatments surgeries other like super basic needs right right this just feels like huge that way i think a fun bit for the show would be to just do a bunch of table setting and like caveats and then just never get to the topic another thing we want to say right off the bat we have gotten dangerously close to an entire episode of caveats we're working toward it so for part one we're just going to talk about the drug itself we're going to talk about semaglotide which is the active ingredient in ozempic and we govi ozempic and wegovi are injections that are produced by novo nordisc which is a big pharmaceutical company they're part of a group of medications that are called glp1 agonists glp1 helps regulate our hunger and satiety signals and production of other hormones like insulin there are other glp1 agonists sort of on the market most of them approved for diabetes treatment.
[00:07:02.640 --> 00:07:08.960] Those are Rebellsis, Majaro, and there are about another dozen that are sort of coming down the pipeline.
[00:07:09.280 --> 00:07:13.040] Semaglotide has been on the market as a treatment for type 2 diabetes in the u.S.
[00:07:13.000 --> 00:07:15.760] since 2018 under the name ozempic.
[00:07:15.760 --> 00:07:21.200] When it's prescribed for weight loss, it's prescribed under the name Wegovi.
[00:07:21.520 --> 00:07:24.000] It's the same thing, they're just different doses.
[00:07:24.000 --> 00:07:28.960] Interestingly, the weight loss one requires a slightly higher dosage of samaglatide.
[00:07:29.520 --> 00:07:33.520] So this drug started to be sort of studied.
[00:07:34.000 --> 00:07:42.000] Its glimmers begin in 1984 with an endocrinologist at the University of Toronto.
[00:07:42.000 --> 00:07:42.960] His name is Dr.
[00:07:42.960 --> 00:07:49.920] Daniel Drucker, and he discovers a new hormone in humans, which is GLP-1.
[00:07:49.920 --> 00:07:53.760] It's called glucagon-like peptide 1.
[00:07:53.760 --> 00:07:54.880] Girl glucagon.
[00:07:55.040 --> 00:08:07.200] As he and other researchers tried to figure out how GLP-1 functioned in the human body, it starts to show real promise as a treatment for type 2 diabetes, but they have this problem.
[00:08:07.520 --> 00:08:12.720] GLP-1 sort of disappears from your system very quickly.
[00:08:13.200 --> 00:08:17.120] So it makes it really hard to study, much less sort of reproduce it.
[00:08:17.120 --> 00:08:23.920] So they start looking for alternate sources of GLP-1 that might last a little longer than the human version, right?
[00:08:24.400 --> 00:08:28.960] And that's when the Gila monster comes in.
[00:08:28.960 --> 00:08:29.360] Oh.
[00:08:29.520 --> 00:08:33.280] Mike, have you ever heard of the Gila monster?
[00:08:33.280 --> 00:08:35.120] Yeah, they're like a cute little lizard.
[00:08:35.120 --> 00:08:39.840] They're like a kind of like a thick, like robust lizard.
[00:08:39.840 --> 00:08:42.240] I did not know about them before this episode.
[00:08:42.240 --> 00:08:43.600] I didn't know a thing about them.
[00:08:43.600 --> 00:08:46.000] They're the largest lizard in North America.
[00:08:46.000 --> 00:08:47.360] They're almost two feet.
[00:08:47.360 --> 00:08:50.240] I've never seen one in real life, but I've seen them in zoo books and they're really cute.
[00:08:50.240 --> 00:08:51.360] Well, listen, Dr.
[00:08:51.360 --> 00:08:55.120] Drucker had one shipped to him in Toronto.
[00:08:55.120 --> 00:08:55.600] Okay.
[00:08:56.240 --> 00:09:05.080] Because it goes through long periods without food, and it has the ability to slow down its appetite and metabolism.
[00:09:05.080 --> 00:09:05.720] Okay.
[00:09:05.720 --> 00:09:09.320] And Drucker wanted to know how they were able to do that.
[00:09:09.320 --> 00:09:21.480] And he discovers that those Gila monsters have genes for something called Extendin 4, which, when sort of synthesized in a lab, eventually became ozempic.
[00:09:21.480 --> 00:09:24.760] How ironic that a thick lizard gave us thin women.
[00:09:24.760 --> 00:09:25.800] Interesting.
[00:09:26.120 --> 00:09:27.000] Interesting.
[00:09:27.000 --> 00:09:46.280] So researchers don't totally know the mechanism for what makes GLP-1 agonists work the way that they do, but we do know that semaglotide sort of mimics that GLP-1 hormone that is, again, released after you eat.
[00:09:46.280 --> 00:09:52.440] It's part of what makes you feel full, and it's part of what signals your brain that it's time to stop eating.
[00:09:52.440 --> 00:09:58.280] And so it works by you end up eating less because you just basically feel full after each meal.
[00:09:58.280 --> 00:09:58.600] Yeah.
[00:09:58.600 --> 00:10:00.360] So like it triggers your satiety hormones.
[00:10:00.360 --> 00:10:05.480] So like ordinarily you'd be hungry again two hours after breakfast, but now it's like three or four hours after breakfast.
[00:10:05.480 --> 00:10:10.200] And so over the course of a day, you just end up eating like, I don't know, 20, 30% less.
[00:10:10.200 --> 00:10:10.680] Yes.
[00:10:10.680 --> 00:10:14.440] And on top of that, it's holding that food longer in your stomach.
[00:10:14.440 --> 00:10:18.440] So you are physically full for a longer period of time, right?
[00:10:19.080 --> 00:10:23.000] And it's triggering a release of insulin.
[00:10:23.000 --> 00:10:29.880] And also, it may help grow pancreatic beta cells, which are the cells that produce and release insulin.
[00:10:29.880 --> 00:10:34.840] So it's not just that it helps you release insulin in the short term.
[00:10:34.840 --> 00:10:38.440] It's also sort of like building up your ability to release insulin in the middle.
[00:10:38.520 --> 00:10:38.920] Oh, interesting.
[00:10:38.920 --> 00:10:39.880] So it's like flexing a muscle.
[00:10:39.880 --> 00:10:41.960] It's actually like building the muscle that secretes insulin.
[00:10:42.120 --> 00:10:42.840] It seems like it.
[00:10:42.840 --> 00:10:43.960] It seems like it might be.
[00:10:44.120 --> 00:10:51.520] The results for people with diabetes in clinical trials are really incredible.
[00:10:52.080 --> 00:10:58.800] So for diabetic people, the most important measure of your blood glucose is your A1C.
[00:10:58.800 --> 00:11:08.160] That's a measure of the amount of hemoglobin in your blood that reflects your blood glucose levels over the last like few months.
[00:11:08.400 --> 00:11:17.200] Most guidance for people with type 2 diabetes suggests that they should keep their A1C below 7 to minimize complications.
[00:11:17.200 --> 00:11:25.840] But people whose blood sugar isn't well managed can have A1Cs that are like 10, 11, 12, 13, like really high.
[00:11:25.840 --> 00:11:35.600] It can lead to damage to that person's eyes, including possible blindness, their kidneys, including kidney failure, to their nerves and to their heart.
[00:11:35.760 --> 00:11:42.880] With the introduction of these GLP-1 agonists, the results are kind of miraculous.
[00:11:43.360 --> 00:11:55.360] There are stories that are told about the initial presenting of the research on these at the American Diabetes Association conference, and people were weeping and gave it a standing ovation.
[00:11:55.360 --> 00:11:55.840] No, I.
[00:11:56.400 --> 00:12:02.720] Because what they're talking about is people whose A1Cs went from like 11 to 7, right?
[00:12:02.720 --> 00:12:12.160] From like really heightened, urgent risk down to like a pretty safe range just with this one drug, right?
[00:12:12.480 --> 00:12:21.760] I do think one of the fundamental like difficult things to process about any of these kinds of health conditions is that, like, we all kind of hate pharmaceutical companies.
[00:12:21.760 --> 00:12:26.960] Like, under a system of capitalism, it's like these are big global profit-maximizing entities.
[00:12:26.960 --> 00:12:31.080] But then, on the other hand, they deliver a product that is genuinely life-saving.
[00:12:31.080 --> 00:12:31.400] Yeah.
[00:12:31.400 --> 00:12:35.640] I know we just get kind of weird whenever people like praise pharmaceutical companies.
[00:12:29.920 --> 00:12:36.520] I'm like, I don't know about that.
[00:12:36.840 --> 00:12:41.720] But then, whenever people overly criticize pharmaceutical companies, I'm also like, I don't know either.
[00:12:41.720 --> 00:12:48.120] So, in the trials for Ozempic, they start noticing pretty significant weight loss.
[00:12:48.120 --> 00:12:52.680] And researchers start going, well, what if we could just use this as a weight loss drug?
[00:12:52.680 --> 00:12:54.520] So, they created Wegovi.
[00:12:54.520 --> 00:12:56.760] It's the same drug at a higher dose.
[00:12:56.760 --> 00:13:00.280] It uses more of the active ingredients, semaglatide.
[00:13:00.280 --> 00:13:03.720] And because of that, it costs more.
[00:13:03.720 --> 00:13:08.120] Diabetic version hovers at around $900 a month.
[00:13:08.120 --> 00:13:09.560] And it costs more for weight loss.
[00:13:09.560 --> 00:13:14.680] It costs like $1,300 a month out of pocket, and most insurers do not cover it.
[00:13:14.680 --> 00:13:30.200] Not that, like, my main purpose with this show is to widen the availability of weight loss drugs, but like there is something fascinating about how we've gotten all this stuff about like the obesity epidemic is so bad, it's like killing our kids, and then it's like we get a drug that ostensibly treats it, and they're like, that's too expensive.
[00:13:30.200 --> 00:13:38.440] Yeah, it is really wild that this is an issue where we like talk out of both sides of our mouths constantly as a culture.
[00:13:38.760 --> 00:13:48.040] In a lot of ways, the experiences of people who are taking Wegovi for weight loss or Manjaro or Rebelsis or whatever the other ones are that are getting prescribed off-label, right?
[00:13:48.360 --> 00:13:52.920] That like a lot of folks are being told that they're like taking the easy way out.
[00:13:52.920 --> 00:13:54.280] Yeah, that's really bizarre.
[00:13:54.280 --> 00:14:01.600] That's the kind of rhetoric that reveals itself to be not about concern, not about your health.
[00:14:02.320 --> 00:14:06.520] Just about, I want you to suffer for looking the way that you look.
[00:14:06.520 --> 00:14:07.720] We're doing discourse, Aubrey.
[00:14:07.720 --> 00:14:08.040] We're doing this.
[00:14:08.200 --> 00:14:11.080] We're doing discourse, and we're not even into the discourse.
[00:14:11.240 --> 00:14:11.920] I know, we haven't weighiovovovov.
[00:14:12.120 --> 00:14:14.360] Michael, I know, I know.
[00:14:14.360 --> 00:14:17.680] I'm keeping my discourse powder dry, but here we are.
[00:14:14.680 --> 00:14:18.400] We're discoursing.
[00:14:18.960 --> 00:14:25.040] So Wegovi was approved for weight loss by the FDA in June 2021.
[00:14:25.360 --> 00:14:33.920] Almost as soon as Wegovi was approved for weight loss, both Wegovi and Ozempic went into shortage.
[00:14:34.320 --> 00:14:47.040] That impacts both people seeking the drug for weight loss and the people using it to manage their blood glucose for diabetes, because what happens is that Wegovi goes into shortage first, right?
[00:14:47.040 --> 00:14:48.640] That's the weight loss one.
[00:14:48.880 --> 00:14:56.720] And then doctors start prescribing Ozempic, the diabetes medication, off-label to people who want to start to lose weight.
[00:14:57.440 --> 00:15:00.480] Then that goes into shortage too.
[00:15:01.360 --> 00:15:10.240] So as we record this, Wegovi and Ozempic are both in shortage, according to the FDA's sort of drug shortage database.
[00:15:10.720 --> 00:15:26.560] When a drug goes on the FDA's shortage list, the FDA then allows what are called compounding pharmacies to mix up what is basically their own version of that drug without prior FDA approval or screening.
[00:15:27.120 --> 00:15:38.560] When Ozempic and Wegovi went into shortage, compounding pharmacies across the country started compounding their own versions of samaglatide.
[00:15:39.200 --> 00:15:46.720] Here's the problem: Novo Nordisk has patented the samaglatide molecule.
[00:15:46.720 --> 00:15:47.280] Oh.
[00:15:47.280 --> 00:15:51.840] And only they can produce it until 2032.
[00:15:51.840 --> 00:15:57.880] So the active ingredient simply isn't available to those compounding pharmacies.
[00:15:57.600 --> 00:15:58.120] Wow.
[00:15:58.320 --> 00:16:01.400] These compounding pharmacies are prescribing something.
[00:16:01.400 --> 00:16:03.800] They're calling it samaglatide.
[00:15:59.920 --> 00:16:04.040] Okay.
[00:16:04.680 --> 00:16:08.680] It's not ozempic and it's not we govie.
[00:16:08.680 --> 00:16:12.280] It might be a watered-down dose of those things.
[00:16:12.600 --> 00:16:16.120] It could be something called samaglatide sodium.
[00:16:16.120 --> 00:16:16.520] Okay.
[00:16:16.520 --> 00:16:24.280] It's called samaglatide, but it's used in lab animal experiments and is not cleared for use in humans.
[00:16:24.280 --> 00:16:33.960] Oh, that's like when people were taking like horse antibiotics that you could buy on Amazon because they couldn't get like human antibiotics because they're like roughly the same thing.
[00:16:33.960 --> 00:16:38.440] Well, except this is not roughly the same thing and is hazardous to humans' health.
[00:16:38.440 --> 00:16:43.480] Samaglatide sodium is not cleared for use in humans because it is bad for humans.
[00:16:43.480 --> 00:16:44.440] Oh, fuck.
[00:16:44.440 --> 00:16:52.600] And the third option is that it's something else entirely because this is in shortage and because there is less FDA oversight.
[00:16:52.920 --> 00:16:59.800] These compounding pharmacies are not required to tell anyone what's in the drugs that they are giving people.
[00:17:00.200 --> 00:17:01.720] This may sound niche.
[00:17:01.720 --> 00:17:04.280] These compounding pharmacies may sound niche.
[00:17:04.280 --> 00:17:13.960] This is every web advertisement you see that says Ozempic for $99 a month or $499 a month or whatever.
[00:17:14.280 --> 00:17:20.520] All of these, all of the little startups that are like, just call and talk to a doctor and you'll have it the next day.
[00:17:20.840 --> 00:17:25.800] All of that stuff is powered by compounding pharmacies.
[00:17:25.800 --> 00:17:26.920] No way.
[00:17:27.240 --> 00:17:39.320] So this got so bad, the compounding pharmacy stuff has gotten so bad that the FDA has issued a number of official warnings about this and specifically has warned against buying from these startups.
[00:17:39.320 --> 00:17:41.400] This is such a bizarre system.
[00:17:41.400 --> 00:17:42.840] It's so weird.
[00:17:42.840 --> 00:17:53.840] It's like there's a shortage of this drug, so we're just gonna like let people buy it from like weird fly-by-night carnival barker ass companies selling whatever the fuck on the internet.
[00:17:53.920 --> 00:17:55.360] We're not gonna regulate it at all.
[00:17:55.360 --> 00:18:00.080] There's not an enforcement mechanism beyond these letters so far, right?
[00:18:00.080 --> 00:18:05.040] Like they're not they're not doing more than that yet, at least not in reporting.
[00:18:05.040 --> 00:18:07.760] Do you have any sense of like when this could resolve itself?
[00:18:07.760 --> 00:18:11.680] Like as Novo Nortis said that they're massively ramping up production?
[00:18:11.680 --> 00:18:15.680] Basically the goalposts just keep getting moved for when the shortage will end.
[00:18:15.680 --> 00:18:17.680] You know, I checked a couple months ago.
[00:18:18.000 --> 00:18:20.000] It said it would be over by the fall.
[00:18:20.000 --> 00:18:22.400] I checked again, it said it would be over by the end of the year.
[00:18:22.400 --> 00:18:23.920] Oh, it's like self-driving cars.
[00:18:23.920 --> 00:18:25.280] It's always five years away.
[00:18:25.600 --> 00:18:27.040] Right on the horizon.
[00:18:27.360 --> 00:18:34.560] As we're talking about these compounding pharmacies, big weight loss companies are buying up these startups.
[00:18:35.360 --> 00:18:40.640] Weight Watchers bought one of these and their stock price jumped almost 60% in a day.
[00:18:40.640 --> 00:18:43.120] Oh, from like 12 cents to like 16 cents or something.
[00:18:43.360 --> 00:18:49.280] I mean, listen, Weight Watchers stock was not doing great, but a 60% increase is a 60% increase, you know?
[00:18:49.280 --> 00:18:51.280] They've gone from a limp to a gate.
[00:18:51.280 --> 00:19:16.080] And I would say, because the discourse around this is all focused on like the real housewives are taking it and frivolous rich people and celebrities are taking it, it makes the issue seem like it isn't incredibly pressing and important, particularly for people with type 2 diabetes, particularly for people who can't access healthcare and other basic needs at their current weight.
[00:19:16.320 --> 00:19:28.320] This is the other thing about this discourse that drives me utterly fucking bananas is that there's not meaningful acknowledgement of the straight-up income barriers to getting this medication.
[00:19:28.720 --> 00:19:41.480] That this is a shortage that is largely presumably created by people with the disposable income to pay out of pocket for a weight loss medication that almost no insurers are covering.
[00:19:41.480 --> 00:19:41.960] Right.
[00:19:41.960 --> 00:19:44.120] You and I have discussed this until we're blue in the face.
[00:19:44.120 --> 00:19:51.960] Like neither one of us wants to litigate individual behaviors, but like that is one that really doesn't sit right with me.
[00:19:51.960 --> 00:19:53.640] My views on this are also very contingent.
[00:19:53.640 --> 00:20:00.920] Honestly, like once we get to a point where these are super duper available, if you want to take one to lose 10 pounds, genuinely, I don't give a shit.
[00:20:00.920 --> 00:20:03.240] In the same way, I don't give a shit if you want to get a nose job.
[00:20:03.240 --> 00:20:05.480] Yeah, but like in time of a shortage.
[00:20:05.480 --> 00:20:05.960] The same thing.
[00:20:05.960 --> 00:20:07.400] There's an Adderall shortage.
[00:20:07.400 --> 00:20:10.680] If you're not prescribed Adderall, don't take Adderall right now.
[00:20:10.680 --> 00:20:16.920] If you don't need Sriracha, I've been doing my part in buying slightly less sriracha than usual.
[00:20:16.920 --> 00:20:21.720] Dude, the Sriracha shortage has been a big topic of conversation in our household.
[00:20:21.720 --> 00:20:22.360] Are you still doing it?
[00:20:22.360 --> 00:20:24.600] Can I cancel you for eating sriracha in a time of need?
[00:20:24.600 --> 00:20:25.480] We had a bottle.
[00:20:25.480 --> 00:20:27.000] It was about halfway done.
[00:20:27.160 --> 00:20:28.360] I got another one.
[00:20:28.360 --> 00:20:29.480] Hypocrite.
[00:20:29.480 --> 00:20:30.200] Totally.
[00:20:30.200 --> 00:20:32.040] You're hoarding sriracha.
[00:20:32.040 --> 00:20:33.640] One and a half bottles.
[00:20:33.640 --> 00:20:35.640] Come take them from my cold dead end.
[00:20:35.800 --> 00:20:37.000] No, I'm just kidding.
[00:20:37.320 --> 00:20:48.760] So, Michael, this is unusual for us, but this topic was so big and expansive that you and I both actually researched this one.
[00:20:48.760 --> 00:20:52.840] And I dug in on sort of the discourse side and the reporting side.
[00:20:52.840 --> 00:20:55.000] And you really dug in on the research side.
[00:20:55.000 --> 00:20:59.480] So can you walk us through just like, what do we know from the research?
[00:20:59.480 --> 00:21:10.040] This is a weird format break for us because ordinarily, like one of us researches and one of us listens, but like it would be odd to pretend that we haven't both been following this like obsessively for the last couple months.
[00:21:10.040 --> 00:21:10.440] Yes.
[00:21:10.440 --> 00:21:20.560] I have deliberately avoided the discourse because I find the discourse annoying, but I have been following the research and like I have a literal spreadsheet of like the various studies that have been done.
[00:21:20.880 --> 00:21:25.840] And for these drugs, there's actually a quite finite amount of information.
[00:21:25.840 --> 00:21:33.840] And I just for the love of God, just want to like walk through what we know and what we can expect from these drugs.
[00:21:33.840 --> 00:21:34.800] Yeah, sounds great.
[00:21:34.800 --> 00:21:50.320] So basically, the trials of samaglatide for weight loss are all grouped under this heading of the STEP trials, which is the samaglatide treatment effect in people with obesity, which should be step-o, but is actually step.
[00:21:50.320 --> 00:21:53.280] Stepo, what, the fifth Marks Brother?
[00:21:55.920 --> 00:22:01.280] And these are sort of classic pharmaceutical company randomized control trials.
[00:22:01.280 --> 00:22:02.720] They are global.
[00:22:02.720 --> 00:22:05.040] They comprise 5,000 people.
[00:22:05.040 --> 00:22:06.960] All of them are 68 weeks long.
[00:22:06.960 --> 00:22:08.240] One of them is a little bit longer.
[00:22:08.240 --> 00:22:09.280] We'll get to it.
[00:22:09.280 --> 00:22:12.240] They are funded by Novo Nordisk, of course.
[00:22:12.240 --> 00:22:16.000] And the way that they structure these, they sort of do it like moon missions.
[00:22:16.000 --> 00:22:18.960] You know, there's like Apollo 1 and Apollo 2.
[00:22:18.960 --> 00:22:27.120] These large pharmaceutical trials are like there's step one, step two, step three, and they break them down into like specific things that they want to know.
[00:22:27.120 --> 00:22:33.280] And step one, step two, step three are not different phases in the same study, right?
[00:22:33.280 --> 00:22:35.040] They are separate studies.
[00:22:35.040 --> 00:22:41.680] So step one is like the overall, just like we're going to give fat people samaglatide for weight loss.
[00:22:41.680 --> 00:22:45.040] Step two is the same thing, but on people with type 2 diabetes.
[00:22:45.040 --> 00:22:49.920] Step three is samaglatide with intensive behavioral therapy.
[00:22:49.920 --> 00:22:50.720] BLTs!
[00:22:50.960 --> 00:22:53.840] And then the rest are kind of like smaller shading.
[00:22:53.840 --> 00:23:01.080] So step four is they put people on samaglatide for a while and then they switch half of them to a placebo.
[00:23:01.240 --> 00:23:03.560] Step five is a two-year trial.
[00:23:03.560 --> 00:23:08.360] Step six and seven are the same thing, but they're done on Japanese, South Korean, and Chinese people.
[00:23:08.360 --> 00:23:13.720] And step eight is testing samaglatide versus one of the other GLP1s.
[00:23:13.720 --> 00:23:16.440] So it's samaglatide versus laraglotide.
[00:23:16.440 --> 00:23:33.000] So when you say step six and step seven are focusing on East Asian folks, it's worth mentioning that most of these trials for Wegovi in particular are just overwhelmingly white, as many diet studies are.
[00:23:33.640 --> 00:23:47.000] One of the sort of leading meta-analyses of studies involving over 11,000 participants was 80% white, 10% black, and 5% AAPI.
[00:23:47.000 --> 00:23:53.080] Although for diet studies, I mean, we both see diet studies that are like 97% white fairly frequently.
[00:23:53.080 --> 00:23:56.600] So like, it's funny, like 80% white, I'm like, ooh, not bad.
[00:23:57.560 --> 00:23:59.320] The bar is in hell.
[00:23:59.320 --> 00:24:03.960] Yeah, like by the standards of fucking diet research, it's like, oh, very diverse sample.
[00:24:04.440 --> 00:24:10.360] The results of these samaglatide trials are like quite consistent, like remarkably consistent.
[00:24:10.360 --> 00:24:17.720] So roughly 80% of people who take samaglatide lose some amount of weight, roughly 5% of their body weight.
[00:24:17.720 --> 00:24:23.400] And roughly half of people who take samaglatide lose 10 to 15% of their body weight.
[00:24:23.400 --> 00:24:27.240] So like a one in two chance of losing like a moderate amount of weight.
[00:24:27.240 --> 00:24:44.120] And then the biggest number and the thing that has like sent the entire like weight loss industry into overdrive on this is that roughly one-third of people who take samaglatide lose more than 20% of their body weight, which is roughly on par with like bariatric surgery.
[00:24:44.360 --> 00:24:50.000] And then another thing that is like a pretty big deal about these drugs is that like the results seem to hold up.
[00:24:50.320 --> 00:24:59.600] So there's one trial where people took samaglatide for two years, and like by the end of it, 36% of people had lost more than 20% of their body weight.
[00:24:59.600 --> 00:25:06.880] So for about a third of patients, they're losing maybe three times as much weight as previous interventions.
[00:25:06.880 --> 00:25:11.440] We should also note that there are pretty significant health effects of these drugs.
[00:25:11.440 --> 00:25:20.080] So even in the shorter-term trials, people have better blood pressure, they have better cholesterol, they have improved A1C levels.
[00:25:20.080 --> 00:25:29.200] We also, with the longer-term trials, we've seen modest, but also kind of big deal reduction in heart attacks and strokes.
[00:25:29.200 --> 00:25:31.440] So that's really exciting.
[00:25:31.440 --> 00:25:31.760] Yeah.
[00:25:31.760 --> 00:25:37.840] If there is a drug that people can take and they are less likely to die, I am pro that drug.
[00:25:37.840 --> 00:25:41.600] I actually looked this up that it's roughly in line with the effect of statins.
[00:25:41.760 --> 00:25:43.760] So this is genuinely like a big deal.
[00:25:43.760 --> 00:25:45.840] Like even if you take the weight loss stuff off the table.
[00:25:45.840 --> 00:25:46.320] Yeah.
[00:25:46.320 --> 00:25:49.040] We should also talk about the side effects.
[00:25:49.040 --> 00:25:52.880] The side effects of the drugs seem to be almost universal.
[00:25:52.880 --> 00:26:01.200] Some studies find, I think the lowest one I found was like 60% of people have like gastrointestinal symptoms, but then some of them are finding like 93% of people.
[00:26:01.200 --> 00:26:14.080] So it's like nausea, constipation, diarrhea, vomiting, the sort of tummy stuff that you would associate with like pretty significantly fucking with your like hunger and satiety hormones.
[00:26:14.080 --> 00:26:27.760] In addition to all of those side effects, there is sort of this whole class of side effects that get covered mostly in like beauty media and like gossip blogs like Ozempic Face.
[00:26:27.760 --> 00:26:29.600] Have you heard about Ozempic Face?
[00:26:29.720 --> 00:26:32.440] From you like 10 minutes ago, right when we started recording.
[00:26:32.600 --> 00:26:37.880] Looks some of us were trying to keep the illusion alive, Michael.
[00:26:38.520 --> 00:26:44.280] So it's basically just the appearance of aging when taking Ozempic.
[00:26:44.280 --> 00:26:46.200] And it's just the result of rapid weight loss.
[00:26:46.200 --> 00:26:48.840] However, you did it, it's not unique to Ozempic.
[00:26:48.840 --> 00:26:53.000] It's just when you lose a lot of weight really quickly, you end up with loose skin.
[00:26:53.000 --> 00:26:53.240] Right.
[00:26:53.240 --> 00:26:55.720] And some of that loose skin will be on your face.
[00:26:55.720 --> 00:26:59.000] And that is also the same kind of thing that happens when people age.
[00:26:59.000 --> 00:26:59.880] So you look older.
[00:26:59.880 --> 00:27:02.280] So Ozempic face is just like you lost weight face.
[00:27:02.280 --> 00:27:02.840] Yeah, totally.
[00:27:03.320 --> 00:27:08.920] These ones just strike me, as we were talking about beforehand, like these ones just strike me as so fucking mean.
[00:27:08.920 --> 00:27:12.360] It's also so fucked up because it's like our culture is telling you to lose weight all the fucking time.
[00:27:12.360 --> 00:27:14.200] And it's like you finally do lose weight.
[00:27:14.200 --> 00:27:15.640] It's like, what's happening to your face?
[00:27:15.640 --> 00:27:16.200] Yeah, totally.
[00:27:16.200 --> 00:27:25.400] Well, and people treat it as like some kind of like comeuppance for like taking a drug or daring to lose weight or being too vain or what, like whatever.
[00:27:25.400 --> 00:27:28.040] Like it's just steeped in so much judgment.
[00:27:28.040 --> 00:27:28.280] Right.
[00:27:28.280 --> 00:27:30.840] That I'm like, could we just set that one down?
[00:27:30.840 --> 00:27:35.400] There's also a bunch of like very rare side effects.
[00:27:35.400 --> 00:27:38.920] So there's been some worry about pancreatitis.
[00:27:38.920 --> 00:27:45.560] Some trials find that it like increases, but then there's a trial of the araglatide that finds that it actually decreases.
[00:27:45.560 --> 00:27:51.800] There's concern about thyroid cancer, but that's based on rodent studies.
[00:27:51.800 --> 00:27:58.520] And there haven't been any signs of that in the data, but we don't know kind of any longer than one and a half to two years.
[00:27:58.840 --> 00:28:05.480] There's slightly elevated rates of gallbladder disease, acute kidney injury.
[00:28:05.480 --> 00:28:14.360] There's two cases in Iceland of suicidal ideation, and the European Medicines Agency is now looking into that.
[00:28:14.480 --> 00:28:29.120] And just this week, the FDA updated the label on samaglatide to include this thing ileus, which is basically when like digested food builds up in your intestine and backs up.
[00:28:29.440 --> 00:28:34.000] And the only way to deal with it is surgery and it's fatal.
[00:28:34.000 --> 00:28:40.160] So we have 33 cases of this that have been reported to the adverse events database and two deaths.
[00:28:40.640 --> 00:28:49.120] But we don't sort of know what to make of those things because the adverse events database is like, as we've discussed on the show before, it's like anyone can submit cases.
[00:28:49.120 --> 00:28:50.720] So it's basically just like a hotline.
[00:28:51.040 --> 00:28:53.840] And so it's something that is like people are looking into more.
[00:28:53.840 --> 00:29:02.880] And there's a study out of China last year that shows that this mechanism exists in mice, where it like basically stops bowel function.
[00:29:02.880 --> 00:29:12.800] And there was some kind of warning in that study of like, oh, this might show up in humans and it might show up around the sort of 18-month mark, meaning like after these studies would have concluded.
[00:29:12.800 --> 00:29:16.160] But that's also like animal studies, super preliminary.
[00:29:16.160 --> 00:29:16.720] We don't know.
[00:29:16.720 --> 00:29:19.680] It's sort of like people don't really know what to make of this yet.
[00:29:19.680 --> 00:29:32.480] Yeah, and you know, two people dying is nothing to context of previous diet drugs having sort of gone this way.
[00:29:32.480 --> 00:29:32.720] Yeah.
[00:29:33.280 --> 00:29:39.040] But then one thing that really stood out to me was, you know, we have these like near universal side effects.
[00:29:39.040 --> 00:29:42.560] We have these like much more rare, much more severe side effects.
[00:29:42.560 --> 00:29:45.600] But the dropout rates in these studies are like really low.
[00:29:45.920 --> 00:29:52.000] What you find in most of the studies is almost everybody is getting some side effect or another.
[00:29:52.000 --> 00:29:56.000] And they typically happen in the first couple weeks of the study when you're like upping your dose.
[00:29:56.000 --> 00:30:04.360] It actually takes four months to get up to the 2.4 milligrams like weight loss dose, but it typically goes away as people kind of get used to the drugs.
[00:30:04.680 --> 00:30:15.000] And so, in the two-year study, there were 150 people who completed the two-year trial, and only 10 of them dropped out due to adverse effects, which is only 6%.
[00:30:15.320 --> 00:30:25.160] So, like, what this indicates is that people are getting side effects, but most, like, the vast majority of people are willing to push through the side effects and complete these trials.
[00:30:25.160 --> 00:30:33.240] Yeah, so what you're saying is folks are more likely to stay in these studies than other studies into sort of like how folks can lose weight.
[00:30:33.240 --> 00:30:33.720] Yes.
[00:30:34.040 --> 00:30:43.640] So, so far, I've kind of been presenting like the case for samaglatide, like the way that you read about it in these clinical trials.
[00:30:43.640 --> 00:30:47.720] I've been reading a lot of things from like, you know, people in like the weight loss world.
[00:30:47.720 --> 00:30:50.760] And like, this is how they talk about the drug, right?
[00:30:50.760 --> 00:30:53.640] Is that it's delivering very significant weight loss.
[00:30:53.640 --> 00:30:56.040] The dropout rates are relatively low.
[00:30:56.040 --> 00:31:04.680] And before we get to like complicating that picture a little bit, I think it's important to first of all just like acknowledge that like that is the data that we have.
[00:31:04.680 --> 00:31:08.840] And like, I think this new generation of weight loss drugs is like genuinely just a big deal.
[00:31:09.000 --> 00:31:21.240] At the same time, to me, like the most bizarre thing about the discourse, especially recently, but you know, since the results of these trials started coming out, is like the weird victory lap that people have been doing.
[00:31:21.240 --> 00:31:24.760] It's like, okay, we know we have something now that works for weight loss, right?
[00:31:24.760 --> 00:31:27.400] We finally have an effective weight loss drug.
[00:31:27.400 --> 00:31:32.600] And then there's this weird sort of second-order thing where they're like, what are the fat activists gonna do now?
[00:31:32.840 --> 00:31:34.840] Like, this ruins body positivity.
[00:31:34.840 --> 00:31:40.360] And there's all this weird shit of like, well, now we have a cure for obesity, right?
[00:31:40.360 --> 00:31:46.000] And I feel like just to sort of take these results as we've been presented with them, right?
[00:31:46.000 --> 00:31:49.920] Like the quote unquote best possible version of these events, right?
[00:31:44.680 --> 00:31:52.080] All of the weight loss, all of the benefits, everything.
[00:31:52.400 --> 00:32:03.040] It's like, we're talking about a drug that 50% of people who take it will lose 15% of their body weight.
[00:32:03.040 --> 00:32:06.000] And like, that is not a world without fat people.
[00:32:06.160 --> 00:32:09.440] This is like the aspect of the drug that drives me absolutely fucking nuts.
[00:32:09.440 --> 00:32:12.800] It's not going to end the quote unquote obesity epidemic.
[00:32:12.800 --> 00:32:13.600] It just isn't.
[00:32:14.000 --> 00:32:20.720] We still, as a society, need to work on like stigma against fat people, improving medical care for fat people.
[00:32:20.720 --> 00:32:28.640] All of the things we say on this show are still fucking true if every single person in America loses 15% of their body weight.
[00:32:28.640 --> 00:32:32.560] And that is a dramatic overestimation of what's even about to happen, right?
[00:32:32.880 --> 00:32:41.760] Even if, as you say, even if they work exactly as they are projected to, even if the data doesn't change one bit with future trials.
[00:32:41.760 --> 00:32:42.240] Yeah.
[00:32:42.240 --> 00:32:48.480] Someone my size goes from being 330 pounds to being 280 pounds.
[00:32:48.480 --> 00:32:58.240] That would take me from being a person with an obese BMI to being a person with an obese BMI.
[00:32:58.240 --> 00:32:58.720] Yeah.
[00:32:58.720 --> 00:33:03.760] This whole thing about like, you know, is this the end of the obesity epidemic?
[00:33:03.760 --> 00:33:07.440] Like, A, no, it's not, as you've pointed out.
[00:33:07.440 --> 00:33:12.080] But B, that is the meanest fucking thing to say.
[00:33:12.080 --> 00:33:19.200] We currently have this fucking nightmare bullshit, which is like the whole fucking show is dedicated to this, where it's like, a fat person goes into the doctor for a migraine, and they're like, I have a migraine.
[00:33:19.200 --> 00:33:20.600] And the doctor's like, you should go on a diet.
[00:33:20.640 --> 00:33:21.000] Yeah.
[00:33:21.120 --> 00:33:22.800] And then it's like, you haven't asked me what I do.
[00:33:22.800 --> 00:33:24.160] You haven't asked me if I eat fast food.
[00:33:24.160 --> 00:33:25.920] You haven't asked me fucking anything.
[00:33:25.920 --> 00:33:29.280] You're giving me this bullshit ass advice when all I want is fucking advice for my migraine, right?
[00:33:29.280 --> 00:33:29.520] Yeah.
[00:33:29.520 --> 00:33:32.840] We're now going into a scenario where you go into the doctor with a migraine.
[00:33:32.840 --> 00:33:34.040] They're like, you should go on Ozempic.
[00:33:34.120 --> 00:33:34.280] Yeah.
[00:33:29.840 --> 00:33:36.200] And you're like, well, I've already been on Ozempic three times.
[00:33:36.440 --> 00:33:41.320] And I was half, I was one of the half of people who lost less than 10% of my body weight.
[00:33:41.320 --> 00:33:43.480] It was costing me more than my fucking rent.
[00:33:43.480 --> 00:33:44.920] I was having weird side effects.
[00:33:44.920 --> 00:33:48.280] People report like not enjoying food anymore, which is like really sad to think about.
[00:33:48.600 --> 00:33:51.160] And then the minute I went off of it, I gained all the fucking weight back.
[00:33:51.160 --> 00:33:52.920] And I've done that four times.
[00:33:52.920 --> 00:33:56.680] And when I'm going in, you're giving me this generic bullshit fucking advice to go on Ozempic.
[00:33:56.680 --> 00:33:58.440] You haven't asked me whether I've been on it before.
[00:33:58.440 --> 00:33:59.560] You haven't asked me about weight cycling.
[00:33:59.560 --> 00:34:03.640] You haven't asked me whether I tolerate the drug or if it intersects with some like antidepressant that I'm taking.
[00:34:03.880 --> 00:34:08.520] We're just redoing the same fucking thing, except instead of go on a diet, it's go on Ozempic.
[00:34:08.520 --> 00:34:08.840] Yeah.
[00:34:08.840 --> 00:34:16.680] And like in the same way that it's not possible for everyone to go on a fucking diet or they've been on a million already, it's not possible for everyone to go on fucking Ozempic and it's not going to work for everybody.
[00:34:16.680 --> 00:34:24.840] I mean, I told, listen, I told you this off mic, but I think this is the darkest episode that I have researched for us.
[00:34:24.840 --> 00:34:25.720] Yeah, it's really bad.
[00:34:25.880 --> 00:34:28.040] It is really upsetting.
[00:34:28.040 --> 00:34:34.920] And I will say, like, not just on an individual level, but also like systemically.
[00:34:34.920 --> 00:34:38.840] Like, I stopped seeing doctors for like eight years.
[00:34:38.840 --> 00:34:41.240] I've written about this a bunch of times.
[00:34:41.240 --> 00:34:46.120] And that was at the height of like the bariatric surgery craze.
[00:34:46.120 --> 00:34:46.760] Yeah.
[00:34:46.760 --> 00:34:52.520] And that really fucking fueled how doctors would talk to me and what treatments they would offer me.
[00:34:52.520 --> 00:35:04.040] And it was like a very frequent conversation of me being like, hey, I'm 24 and I have an entry-level position at a nonprofit where I feel fortunate to have health coverage at all.
[00:35:04.040 --> 00:35:07.720] No, I don't have 25 grand for a weight loss.
[00:35:08.040 --> 00:35:08.440] Right.
[00:35:08.440 --> 00:35:08.760] Yeah.
[00:35:08.760 --> 00:35:22.560] But that still became a thing, right, amongst healthcare providers who we already know are more likely to think of fat patients as non-compliant, as slovenly, as unattractive, as weak-willed, as all of these things, right?
[00:35:22.560 --> 00:35:28.960] Like, this becomes another reason for that group of people also to stop listening to fat people.
[00:35:29.280 --> 00:35:32.400] Like, it's going to get harder for me to get health care.
[00:35:32.400 --> 00:35:33.040] Right, right.
[00:35:33.040 --> 00:35:34.640] That's part of what's about to happen.
[00:35:35.200 --> 00:35:43.360] This is why I wanted to go out of my way to like insufferably present the results of these trials as if they will hold up.
[00:35:43.680 --> 00:35:51.680] Because even in a world in which that happens, that doesn't call anything into question about the need for equal treatment.
[00:35:51.680 --> 00:35:59.120] And at the same time, the results of these trials are extremely unlikely to pan out in the real world.
[00:35:59.120 --> 00:35:59.920] Yeah, totally.
[00:35:59.920 --> 00:36:10.080] So I have three reasons why these drugs are very unlikely to pan out and deliver like the end of obesity or all the stuff that the insufferable discourse has been telling us.
[00:36:10.400 --> 00:36:12.240] We're tucking into the debunk bed.
[00:36:12.240 --> 00:36:14.880] Yeah, this is much more comfortable space for us.
[00:36:14.880 --> 00:36:21.360] The first is that the populations that are being studied in these trials are actually relatively narrow.
[00:36:21.360 --> 00:36:32.400] So step one, which is the trial that's kind of the overall, like just normal weight loss drugs being given to people, I'm going to read you the exclusion criteria.
[00:36:32.400 --> 00:36:39.200] People were not able to participate in step one if they have a history of major depressive disorder.
[00:36:39.200 --> 00:36:39.520] Okay.
[00:36:39.520 --> 00:36:43.280] They have a diagnosis of a severe psychiatric disorder.
[00:36:43.280 --> 00:36:48.960] They fill out the patient health questionnaire with a score of over 15.
[00:36:48.960 --> 00:36:55.760] This is one of those, one of those questionnaires that has, like, you know, I have feelings of hopelessness, like rank from like every day to like never.
[00:36:55.760 --> 00:36:56.160] Yeah, yeah, yeah, yeah.
[00:36:56.320 --> 00:36:58.800] It's basically a measure of like how depressed you are.
[00:36:58.800 --> 00:37:00.760] It's like, are you feeling tired?
[00:36:59.680 --> 00:37:03.880] One of them is, do you have poor appetite or overeating?
[00:37:03.880 --> 00:37:06.840] Which is like a funny exclusion criteria to include in this.
[00:37:07.000 --> 00:37:32.280] They're also excluding people with a lifetime history of a suicide attempt, any history of myocardial infarction, stroke, hospitalization, any kind of existing cardiovascular stuff, known or suspected abuse of alcohol or recreational drugs, and female who is pregnant, breastfeeding, intends to become pregnant, or is of childbearing age and not using a highly effective contraceptive method.
[00:37:32.280 --> 00:37:35.320] Holy shit, that cuts out so many people, Michael.
[00:37:35.320 --> 00:37:50.280] Well, the thing is, I mean, with these studies, like I sort of get why people who design studies do this stuff, because they want to start with a kind of baseline of like quote unquote normal people without a bunch of like pre-existing conditions, which I get for the purpose of a trial.
[00:37:50.280 --> 00:37:53.960] I get why you want to have like a clean, quote-unquote sample.
[00:37:53.960 --> 00:38:00.680] However, once these drugs get out into the real world, they're going to be taken by people with depression.
[00:38:00.680 --> 00:38:05.080] Yeah, like when you're designing a trial like this, I imagine you're walking a real line, right?
[00:38:05.080 --> 00:38:08.520] You want the trial itself to be safe for the people who participate in it.
[00:38:08.520 --> 00:38:18.440] So you want to eliminate things like existing heart conditions, like anything, existing pancreatic conditions, anything sort of related to the mechanisms involved in this drug.
[00:38:18.440 --> 00:38:19.960] I totally get that, right?
[00:38:20.360 --> 00:38:24.920] And you don't want it to make anything worse for anybody, like just on a human level.
[00:38:24.920 --> 00:38:26.760] That totally makes sense to me.
[00:38:26.760 --> 00:38:40.360] The trick is all of that gets translated into an assumption that this is how it will play out for all people who are not being monitored in a study and provided the drug for free.
[00:38:40.360 --> 00:38:40.920] Yeah.
[00:38:40.920 --> 00:38:47.760] And all people who have all of these other conditions that are extremely prevalent in the US, right?
[00:38:44.920 --> 00:38:48.000] Yes.
[00:38:48.320 --> 00:39:04.560] And also, I mean, we, I probably should have started with this, but the second reason why it's unlikely that these are going to deliver on the results that we're seeing in the trials is because there are real-world studies of samaglatide and they don't find the same results.
[00:39:04.800 --> 00:39:11.920] So there's a study in the US that followed like people who went to weight loss clinics and got these drugs for one year.
[00:39:11.920 --> 00:39:17.440] If you remember in the trials of these drugs, the average weight loss was around 15%.
[00:39:17.760 --> 00:39:21.920] In the real world trial, people are losing 7.5% of their body weight.
[00:39:21.920 --> 00:39:31.440] And there are other real-world trials, it's quite remarkable actually, that find almost the same thing that like the weight loss, you know, 80% of people lose 5% of their body weight or more.
[00:39:31.440 --> 00:39:33.840] In the real world, that tends to be around 40%.
[00:39:34.080 --> 00:39:40.480] So almost all of the numbers that we're seeing in these randomized control trials are half once we get to the real world.
[00:39:40.480 --> 00:39:41.600] They're not zero, right?
[00:39:41.600 --> 00:39:49.360] So this still is going to be, again, a big deal, but we're not seeing in the real world those results continue to show up.
[00:39:49.680 --> 00:39:53.440] It's not totally clear why this is happening.
[00:39:53.440 --> 00:40:03.440] One of them appears to be that in the randomized control trials, people aren't just taking the drug, they're also getting like dietary counseling.
[00:40:03.440 --> 00:40:09.360] So one of the trials is like super intensive behavioral therapy where they're like meeting with dietitians once a week.
[00:40:09.360 --> 00:40:17.680] But in all of the other trials, they're doing monthly check-ins with counselors and they're having all of these, you know, bio-markers taken.
[00:40:17.680 --> 00:40:21.200] And I think there's something about like people just being in a study.
[00:40:21.200 --> 00:40:23.920] Like you really want to finish because you're like, oh, I'm part of this like project.
[00:40:23.920 --> 00:40:26.240] And it's like experimental and super cool.
[00:40:26.240 --> 00:40:34.360] And like, the adherence rates for these randomized controlled trials are like significantly higher than we have in the real world.
[00:40:34.520 --> 00:40:45.720] When you look at the real world trials, even among people who have type 2 diabetes and who like really need these drugs, a lot of them are finding like 50% dropout rates after two years.
[00:40:45.720 --> 00:40:48.680] And some of them, one of them, finds 70% dropout rate.
[00:40:48.680 --> 00:41:00.280] You can already see as we're sort of like walking through this research, the gap between the popular claims that are being made about these drugs and what the research actually says.
[00:41:00.280 --> 00:41:02.440] That's where we got to with Fenfen.
[00:41:02.440 --> 00:41:03.960] That's where we got to with Ally.
[00:41:04.120 --> 00:41:16.200] That's where we got to with like, this is sort of a pattern with weight loss drugs: is that we get out over our skis culturally with like this kind of magical thinking excitement stuff.
[00:41:16.760 --> 00:41:22.600] We then make a bunch of policy decisions based on the excitement and not the data.
[00:41:22.920 --> 00:41:34.120] And then we're kind of stuck with these sort of adjusted systems that were, again, changed based on what we thought was possible, not what we were actually seeing.
[00:41:34.120 --> 00:41:34.600] Exactly.
[00:41:34.600 --> 00:41:45.400] And the other thing that, again, we have very good data on is that people tend to regain all of the weight the second they stop taking these drugs.
[00:41:45.720 --> 00:41:52.840] So one of the STEP studies switched people from somaglatide to a placebo at 20 weeks.
[00:41:52.840 --> 00:41:59.000] There's also a trial of another GLP1, Tyrzepatide, these fucking tides, that did the same thing.
[00:41:59.000 --> 00:42:01.960] After 36 weeks, they switched people to a placebo.
[00:42:01.960 --> 00:42:06.120] And basically, it's like people start regaining the weight very quickly.
[00:42:06.120 --> 00:42:09.960] And like within a year, they've regained almost all of the weight.
[00:42:10.120 --> 00:42:17.440] These drugs seem to put people in the same cycle as fad diets, but just with like more dramatic and like longer results.
[00:42:17.760 --> 00:42:24.320] Well, and the people that I have heard talk about taking these drugs are like, I'm just going to take it until I get down to X weight and then I'm going to stop.
[00:42:24.400 --> 00:42:24.880] Yeah, yeah, yeah.
[00:42:25.120 --> 00:42:25.360] Right.
[00:42:25.360 --> 00:42:28.720] And that is people's plan for how this is going to happen.
[00:42:28.720 --> 00:42:31.200] And that's not how these drugs work.
[00:42:31.520 --> 00:42:38.000] I'm seeing this discourse among like weight loss clinicians too, where they're like, well, ultimately it comes down to diet and exercise.
[00:42:38.000 --> 00:42:42.160] And so we need to get people on these drugs and then teach them the diet and exercise stuff.
[00:42:42.160 --> 00:42:45.360] And then once they know that, we can take them off the drugs.
[00:42:45.360 --> 00:42:55.680] But this trial of kerzepatide, the other drug, had people on an intensive behavioral therapy program when they went off the drug.
[00:42:55.840 --> 00:43:04.640] So people took it for a while, then they switched to a placebo while still doing like exercise and like cooking classes and all this stuff that everybody says is so fucking effective.
[00:43:04.640 --> 00:43:06.080] And they gained all the weight back.
[00:43:06.080 --> 00:43:09.520] This is another case of pump the brakes and ask a fat person.
[00:43:09.520 --> 00:43:10.080] Yeah, yeah, yeah.
[00:43:10.320 --> 00:43:11.760] Has anybody tried to teach you how to cook?
[00:43:11.760 --> 00:43:13.520] Has anybody offered you a gym membership?
[00:43:13.520 --> 00:43:16.800] Has anybody told you that your form was wrong while you were working out?
[00:43:16.800 --> 00:43:17.280] Right.
[00:43:17.280 --> 00:43:19.040] This is every day.
[00:43:19.360 --> 00:43:25.200] The reason that people think that in part is that it reinforces our existing beliefs about fat people.
[00:43:25.200 --> 00:43:25.440] Right.
[00:43:25.440 --> 00:43:25.840] Right.
[00:43:26.000 --> 00:43:33.840] Which is just that they're too lazy or they're too unintelligent or they're too uninformed to just do it for themselves.
[00:43:33.840 --> 00:43:36.160] So they need a thin person to teach them how.
[00:43:36.160 --> 00:43:38.160] This is going on my Aubrey Gordon soundboard.
[00:43:38.160 --> 00:43:38.320] Yeah.
[00:43:38.320 --> 00:43:39.120] Step back.
[00:43:39.120 --> 00:43:40.160] Ask a fat person.
[00:43:40.160 --> 00:43:43.680] I mean, genuinely, that's going to be my advice.
[00:43:43.680 --> 00:43:45.200] Like 80% of the time.
[00:43:45.200 --> 00:43:48.080] It's like, have you even talked to a fat person about this?
[00:43:48.080 --> 00:43:56.320] This is another like super fucking familiar pattern where it's like, okay, everyone should go on Atkins because low-fat diets work and then like, or low-carb diets work.
[00:43:56.320 --> 00:44:03.080] And then, of course, after like six months, everyone gains the weight, you know, and then it's like, then it's like, well, if you stayed on it, you would have kept the weight off, which is true.
[00:44:03.080 --> 00:44:03.400] Fine.
[00:44:03.400 --> 00:44:05.320] If you can stay on it, but no one can fucking stay on it.
[00:44:05.320 --> 00:44:05.560] Yeah.
[00:44:05.560 --> 00:44:05.800] Right.
[00:43:59.840 --> 00:44:09.560] We know in the real world, no one can stay on these extreme low-carb diets for very long.
[00:44:09.560 --> 00:44:12.680] So let's move forward on that basis that no one can fucking stay on them, right?
[00:44:12.680 --> 00:44:17.160] And with this, it's going to be the same thing of like, well, Ozempic does work if you can stay on it.
[00:44:17.160 --> 00:44:17.480] Yeah.
[00:44:17.480 --> 00:44:18.920] Okay, but people aren't staying on it.
[00:44:18.920 --> 00:44:22.440] We know from real world data that even when it's fucking free, people are not staying on it.
[00:44:22.440 --> 00:44:26.360] Well, and if you do stay on it, people characterize it as the easy way out.
[00:44:26.360 --> 00:44:27.800] Yeah, and then you have this bullshit.
[00:44:27.800 --> 00:44:27.960] Right?
[00:44:27.960 --> 00:44:31.320] Like Oprah was just saying the other day, like, it's the easy way out.
[00:44:31.320 --> 00:44:32.360] So I'm not going to do it.
[00:44:32.360 --> 00:44:35.800] And I'm like, Oprah, you are in your 60s.
[00:44:35.800 --> 00:44:39.960] How hard do you think you need to have appeared to have tried?
[00:44:39.960 --> 00:44:40.360] Yeah.
[00:44:40.360 --> 00:44:50.760] And then, like, listen, the discourse makes it worse because in the discourse is like a bunch of the reporting is like, we really need to tamp down on the stigma facing people who take Ozempic.
[00:44:50.760 --> 00:44:55.960] And I'm like, is that the stigma that we need to clamp down on?
[00:44:55.960 --> 00:45:01.480] What's so fucking annoying to me about this discourse, you have like successfully radicalized me on this in like the last 72 hours.
[00:45:01.640 --> 00:45:06.120] Oh, hey, as I've been reading this, it's like this shows up everywhere.
[00:45:06.120 --> 00:45:08.360] Like, what about the stigma of taking the drugs?
[00:45:08.360 --> 00:45:12.360] But the stigma of taking Ozempic is fat phobia.
[00:45:12.360 --> 00:45:18.920] It's the same fucking stigma that fat people are facing, but just like, oh, you're taking the easy way out by using a weight loss drug.
[00:45:18.920 --> 00:45:21.800] That's the connection between fatness and virtue.
[00:45:21.800 --> 00:45:24.120] You should lose weight in the virtuous way.
[00:45:24.120 --> 00:45:25.080] Take the stairs.
[00:45:25.080 --> 00:45:26.360] Yeah, take the fucking stairs.
[00:45:26.360 --> 00:45:29.880] It's like, well, you might look thin, but you're really a fat person.
[00:45:30.280 --> 00:45:42.760] You cannot muster any fucking gumption from anybody to like give a shit about stigma against fat people, but they're super chill to invoke fat phobia against people who stop being fat.
[00:45:42.760 --> 00:45:45.040] And they still do the fucking stigma against fat people.
[00:45:44.840 --> 00:45:45.600] And they still do it.
[00:45:45.760 --> 00:45:58.800] It's also been fascinating, I'll say, on the discourse end, that like there have been all of these bizarre hand-wringing pieces from thin people being like, was body positivity for nothing?
[00:45:58.800 --> 00:46:00.400] I know, it was all a lie.
[00:46:00.400 --> 00:46:06.080] The vast majority of fat people were under no illusions about broader social acceptance.
[00:46:06.480 --> 00:46:12.000] At best, people said fewer unwanted things about our bodies.
[00:46:12.000 --> 00:46:13.440] It never stopped.
[00:46:13.440 --> 00:46:15.200] We were never lifted up.
[00:46:15.200 --> 00:46:16.720] We were never centered.
[00:46:16.720 --> 00:46:19.440] We got one lizzo out of it, right?
[00:46:20.080 --> 00:46:21.680] And we don't even have that anymore.
[00:46:21.680 --> 00:46:23.600] And we don't even have that anymore.
[00:46:23.600 --> 00:46:24.720] Like, right?
[00:46:24.720 --> 00:46:33.600] Like, the degree to which this discourse is thin people telling themselves stories that they want to hear.
[00:46:33.600 --> 00:46:40.800] It's funny to me that, like, we like meticulously outline this and planned it out, but neither one of us can resist talking about the discourse.
[00:46:41.280 --> 00:46:42.560] I hate it so much.
[00:46:42.960 --> 00:46:45.600] Like fast-forwarding to hate.
[00:46:46.240 --> 00:46:47.520] Okay, Michael.
[00:46:47.520 --> 00:46:49.200] We've talked about the drug.
[00:46:49.200 --> 00:46:52.960] Let's talk about the manufacturer of the drug.
[00:46:53.120 --> 00:46:53.440] Yeah.
[00:46:53.440 --> 00:46:57.040] Ozempic and Wegovi are both made by Novo Nordisk.
[00:46:57.040 --> 00:46:59.760] It's a big pharmaceutical company from Denmark.
[00:46:59.760 --> 00:47:00.960] From Denmark.
[00:47:00.960 --> 00:47:07.200] And their marketing practices have really set the template for all the discourse we've been seeing since.
[00:47:07.200 --> 00:47:07.520] Okay.
[00:47:07.520 --> 00:47:10.320] Wait, are there ads for Wagovi and Ozempic?
[00:47:10.320 --> 00:47:13.440] You haven't seen the O-O-O-Ozempic?
[00:47:13.440 --> 00:47:15.760] That's like the cover songs that are in all the fucking trailers now.
[00:47:15.760 --> 00:47:20.000] The very slow, brooding cover of like, I whip my hair back and forth.
[00:47:23.200 --> 00:47:27.200] I'm blue, badoo, dee dadu die, but it's like super dark.
[00:47:27.200 --> 00:47:28.160] Yeah.
[00:47:28.800 --> 00:47:34.520] No, as we've discussed many times, we're on very different, like, Instagram experiences and like algorithms.
[00:47:34.600 --> 00:47:38.120] And like, I've never seen an ad for weight loss anything.
[00:47:38.120 --> 00:47:44.440] I'll tell you what, Mike, I might give you homework at one point and be like, go watch a half an hour of TV and tell me what you notice about the ad.
[00:47:44.600 --> 00:47:45.640] Dude, no.
[00:47:47.560 --> 00:47:48.920] Absolutely not.
[00:47:48.920 --> 00:47:53.160] I watch terrestrial TV like once a fucking year when I'm like visiting my grandma.
[00:47:53.160 --> 00:47:56.120] And I'm like, this is like, this is like actively making me stupider.
[00:47:56.120 --> 00:47:58.040] It's like shocking how bad it is.
[00:47:58.040 --> 00:48:02.280] So we're going to talk a little bit about the marketing practices at Novo Nordisk.
[00:48:02.280 --> 00:48:02.600] Okay.
[00:48:02.600 --> 00:48:05.960] There is a lot here that leaves me feeling icky.
[00:48:06.120 --> 00:48:11.400] A very good example of this is a campaign called It's Bigger Than Me.
[00:48:11.400 --> 00:48:12.920] Have you seen this campaign at all?
[00:48:12.920 --> 00:48:14.280] Is it like billboards?
[00:48:14.280 --> 00:48:18.760] There are ads, there are billboards, there are branded segments on TV shows.
[00:48:18.760 --> 00:48:20.360] There are so many things.
[00:48:20.360 --> 00:48:23.720] The slogan is obesity, it's bigger than me.
[00:48:24.520 --> 00:48:35.320] The idea behind the campaign is: it's not your fault you're fat, followed immediately by it's because you have a disease and that disease requires medical treatment.
[00:48:35.560 --> 00:48:38.680] And that medical treatment can only be provided by one company.
[00:48:38.680 --> 00:48:41.400] It's bigger than me, it's $15,000 per year.
[00:48:41.400 --> 00:48:42.040] Yeah, that's right.
[00:48:42.040 --> 00:48:43.000] That's right.
[00:48:43.320 --> 00:48:52.760] As part of this campaign, Novo Nordisk has specifically courted black public figures and particularly black women as spokespeople.
[00:48:52.760 --> 00:48:55.640] Their first spokesperson was Queen Latifah.
[00:48:55.640 --> 00:48:59.880] Their next was Yvette Nicole Brown, who was on Community.
[00:49:00.520 --> 00:49:14.360] Their third was Roland Martin from CNN, who ran an hour-long segment on fatness in black communities that was listed as quote-unquote powered by Novo Nordisk.
[00:49:14.360 --> 00:49:18.480] That's like when influencers say, like, I've partnered with Nike or whatever.
[00:49:14.840 --> 00:49:20.960] It's like, it's just them paying you to say words.
[00:49:21.280 --> 00:49:36.480] Well, and on top of that, the reporting around the quote-unquote, it's bigger than me campaign is just rife with like the most garbage messages about fatness and body positivity and all kinds of stuff.
[00:49:36.480 --> 00:49:41.600] So I read an interview with Yvette Nicole Brown with the Grio.
[00:49:41.600 --> 00:49:47.840] In that interview, she said, quote, being focused on your health does not mean that you're not body positive.
[00:49:47.840 --> 00:49:54.480] I think it's actually the most exemplary way that you can be body positive because you need your body to continue to live.
[00:49:54.480 --> 00:49:57.200] Aubrey, were you just like losing your mind?
[00:49:57.200 --> 00:50:00.160] You hate this body positivity stuff already.
[00:50:00.480 --> 00:50:09.520] This is like, this is reifying everything you've said about the whole body positivity thing that it's all just like they're repackaging the same shit and selling it back to you.
[00:50:09.520 --> 00:50:20.160] The article goes on to say that, quote, Brown said somewhere down the line, society at large developed the idea that if you're body positive, you can't care about physical health.
[00:50:20.800 --> 00:50:25.200] In my notes, I wrote, in all caps, who is saying this?
[00:50:25.200 --> 00:50:26.480] Who fucking said this?
[00:50:27.040 --> 00:50:27.760] Who is saying this?
[00:50:27.760 --> 00:50:29.360] And it's like trolls, right?
[00:50:29.360 --> 00:50:35.840] It's like it's seeding a bad faith argument to be like, we don't think that's true.
[00:50:35.840 --> 00:50:38.320] Look at what all those nutty people are saying.
[00:50:38.320 --> 00:50:39.280] They're wrong.
[00:50:39.280 --> 00:50:44.320] This is like when conservatives are like, feminists don't even want you to get married and have kids.
[00:50:44.320 --> 00:50:48.240] It's the phenomenon that has built Michael Hobbes' Twitter feed.
[00:50:48.240 --> 00:50:49.280] Hey.
[00:50:49.280 --> 00:50:49.680] Hey.
[00:50:50.320 --> 00:50:52.320] You're familiar with my work.
[00:50:52.640 --> 00:51:02.760] So, our third section, Michael, is the part that I have realized is most troubling to me, and that is the discourse.
[00:50:59.920 --> 00:51:06.520] There's been a lot of like garbage media about this in the last like year.
[00:51:06.840 --> 00:51:11.640] Here are three actual fucking headlines from coverage of this.
[00:51:12.200 --> 00:51:17.400] One, will Ozempic change how we think of being fat and thin?
[00:51:17.400 --> 00:51:18.360] Question mark.
[00:51:18.360 --> 00:51:18.920] Okay.
[00:51:18.920 --> 00:51:20.520] Life after food?
[00:51:20.520 --> 00:51:21.400] Question mark?
[00:51:22.040 --> 00:51:25.960] And Ozempic settles the obesity debate.
[00:51:25.960 --> 00:51:26.520] Oh.
[00:51:27.320 --> 00:51:34.760] It is just bad faith proclamations and bullshit question mark headlines, like as far as the eye can see.
[00:51:34.760 --> 00:51:35.000] Yeah.
[00:51:35.400 --> 00:51:47.240] What I am worried about is that when we see a wave of media like we have seen around Ozempic, we also tend to see a wave of increased anti-fat bias, right?
[00:51:47.240 --> 00:51:47.560] Right.
[00:51:47.560 --> 00:51:47.960] Right.
[00:51:47.960 --> 00:51:55.080] And the reporting that I have seen so far, the think pieces that I have seen so far, none of them are grappling with that.
[00:51:55.080 --> 00:51:55.640] Right.
[00:51:55.640 --> 00:52:04.760] Very few people are asking fat people what they need in this moment, and nobody is asking diabetic people what they need in this moment.
[00:52:04.760 --> 00:52:20.040] Like a thing that I experientially know in every bone in my body is that when people I know start to lose weight, the vast majority of them start to see themselves as more virtuous.
[00:52:20.040 --> 00:52:20.520] Yeah.
[00:52:20.520 --> 00:52:26.360] Whether they want to or not, whether they mean to or not, whether or not they would say it out loud.
[00:52:26.360 --> 00:52:26.760] Yeah.
[00:52:26.760 --> 00:52:31.080] It's very common for people to expect social reinforcement for weight loss.
[00:52:31.400 --> 00:52:40.280] And I would say now, as I have said for years now, which is you have got to get people's consent to do that.
[00:52:40.600 --> 00:52:45.000] The best case scenario is that you're sending a message that you're like not a very good friend to a fat person.
[00:52:45.680 --> 00:52:46.160] Right.
[00:52:47.040 --> 00:52:53.840] And the worst case scenario is that you're increasing the stigma that they face and potentially also like triggering people's eating disorders.
[00:52:53.840 --> 00:52:54.240] Yeah.
[00:52:54.240 --> 00:52:57.040] Like this shit is not unthorny.
[00:52:57.040 --> 00:53:00.960] And the fact that you're hearing it everywhere doesn't make it less urgent.
[00:53:00.960 --> 00:53:05.120] I would argue it makes it more urgent to like double up on those boundaries.
[00:53:05.120 --> 00:53:09.440] Like you have got to give fat people an out for this conversation.
[00:53:09.440 --> 00:53:15.760] And we've got to stop presuming that this is like a good and exciting conversation for everybody.
[00:53:15.760 --> 00:53:19.680] I'm like not all that invested in like the drugs themselves.
[00:53:19.680 --> 00:53:20.560] The drugs are the drugs.
[00:53:21.120 --> 00:53:21.520] I don't know.
[00:53:21.520 --> 00:53:22.400] I mean, same, same.
[00:53:22.560 --> 00:53:24.160] Maybe they'll be effective weight loss drugs.
[00:53:24.160 --> 00:53:24.960] Maybe they won't.
[00:53:24.960 --> 00:53:25.760] I don't know.
[00:53:25.760 --> 00:53:35.120] But like, given what we know now, the most likely scenario is that like they're going to be prescribed to millions, potentially tens of millions of people.
[00:53:35.120 --> 00:53:47.680] And like what you said to me the other day is that like you can see the number of people who lost like 15 fucking pounds and then all of a sudden are like really mean to fat people, just like exponentially increasing.
[00:53:47.680 --> 00:54:06.960] The other thing that I will say about the discourse around this is that every like celebratory story about Ozempic that comes out now, that's all going to be mirrored by future panicky think pieces on the rising costs of obesity and how fat people are bankrupting us once again, right?
[00:54:07.040 --> 00:54:16.240] This is an unbelievably expensive medication and all of that is going to come back to scapegoating fat people once again, right?
[00:54:16.240 --> 00:54:20.240] That like right now we're saying it's frivolous housewives and whatever.
[00:54:20.240 --> 00:54:24.320] When we get into the insurance conversations, we're not going to be scapegoating rich people.
[00:54:24.320 --> 00:54:25.920] We generally don't do that.
[00:54:25.920 --> 00:54:29.760] We scapegoat poor people, BIPOC, fat people, queer people.
[00:54:29.960 --> 00:54:30.520] You know what I mean?
[00:54:30.520 --> 00:54:32.520] Like, we've got a list of people we scapegoat.
[00:54:32.520 --> 00:54:40.440] We're also setting ourselves up for another round of excruciating discourse in another couple years when people look around and they're like, wait a minute, there's still fat people.
[00:54:40.440 --> 00:54:40.760] Yeah.
[00:54:40.760 --> 00:54:47.560] All the magazines told me a couple of years ago that this was the end of obesity, and yet people are still fat.
[00:54:47.560 --> 00:54:54.520] We should also say, listen, you will face serious, serious fucking stigma as a person who stays fat.
[00:54:55.080 --> 00:54:59.560] Trust me, a person who has stayed fat through all the interventions, right?
[00:54:59.560 --> 00:55:04.920] Like, I've already sort of started shifting socially.
[00:55:04.920 --> 00:55:20.040] You know, I'm already a very homebody, indoorsy kind of lady, and I'm already restricting who I socialize with pretty dramatically because of this kind of talk and because I'm unwilling to be in spaces where this shit will come up.
[00:55:20.040 --> 00:55:20.440] Yeah.
[00:55:20.440 --> 00:55:20.680] Right.
[00:55:21.000 --> 00:55:27.960] And for me, that means functionally, like a vast majority of people I know who are not fat and some people I know who are.
[00:55:27.960 --> 00:55:28.280] Right.
[00:55:28.280 --> 00:55:28.440] Right.
[00:55:28.440 --> 00:55:35.560] So like, I just want people to understand, like, the stakes of this as a fat person are: I feel like I don't belong in the world.
[00:55:35.560 --> 00:55:35.960] Right.
[00:55:35.960 --> 00:55:41.560] When people talk about how great it's going to be when I'm not around, it's that's not me being too sensitive.
[00:55:41.560 --> 00:55:43.480] That's not fat people taking it too hard.
[00:55:43.480 --> 00:55:45.640] That's you saying plainly, right?
[00:55:45.640 --> 00:55:47.480] Everything will be better when you're gone.
[00:55:47.480 --> 00:55:47.800] Right.
[00:55:48.120 --> 00:55:50.520] And then fat people like taking that message.
[00:55:50.520 --> 00:55:52.280] That's horrible.
[00:55:52.440 --> 00:55:56.520] The fact that you have been through so many rounds of this, it's like, why aren't you on Fenfin?
[00:55:56.600 --> 00:55:58.360] Why aren't you on bariantrosurger?
[00:55:58.360 --> 00:55:59.320] Why aren't you clean eating?
[00:55:59.320 --> 00:56:04.520] Why aren't like all this is just new packaging for like, why aren't you thin?
[00:56:04.520 --> 00:56:04.920] Yeah.
[00:56:04.920 --> 00:56:06.840] And like, that is worth listening to.
[00:56:06.840 --> 00:56:10.280] This isn't like a paranoid fantasy on the part of fat people.
[00:56:10.280 --> 00:56:14.440] This is something that they've been through numerous times over the course of their lifetimes now.
[00:56:15.600 --> 00:56:22.480] We're just doing the same thing again, even when the data does not remotely indicate that we're not going to have fat people anymore.
[00:56:22.480 --> 00:56:23.120] It never has.
[00:56:23.120 --> 00:56:24.480] We're always going to have fat people.
[00:56:24.480 --> 00:56:32.240] And there's always going to be people, whatever the medical intervention is, that can't use it or it doesn't work for them or they've tried it already.
[00:56:32.240 --> 00:56:34.320] That's always going to be the case.
[00:56:34.320 --> 00:56:34.720] Yeah.
[00:56:34.960 --> 00:56:39.920] The fact that people are so obsessed with asking the question, is what's the end of obesity?
[00:56:39.920 --> 00:56:40.720] Like really early.
[00:56:40.720 --> 00:56:41.040] Yeah.
[00:56:41.040 --> 00:56:44.160] Like, oh, is this going to be the reason we don't have fat people around anymore?
[00:56:44.160 --> 00:56:46.080] It's like, it's so fucking telling.
[00:56:46.080 --> 00:56:50.080] So moving forward, we're going to continue to get these drugs.
[00:56:50.080 --> 00:56:53.840] We're going to continue to get this sort of quote-unquote gold rush.
[00:56:53.840 --> 00:57:07.760] And in that time, I think it is worth being extra skeptical and returning to the voices of fat people and diabetic people when media isn't doing that for us, right?
[00:57:08.080 --> 00:57:27.520] To like actually return to the people who are most impacted by this debate and to spend way the fuck less time speculating about Elon Musk and Courtney Kardashian and making celebrities defend themselves and like trying to think through how do we get these drugs to people who need them?
[00:57:27.520 --> 00:57:36.240] How do we design a better discourse that isn't so wildly dehumanizing to fat people and again to diabetic people, right?
[00:57:36.560 --> 00:57:48.640] And like, how do we just show up for people a little bit more around this stuff and interrupt some of this like dancing in the street kind of energy that is like really upsetting to see as a fat person?
[00:57:48.960 --> 00:57:50.640] Okay, we've done enough table setting.
[00:57:50.800 --> 00:57:52.080] Let's start the rest.
[00:57:53.560 --> 00:57:55.080] It's been two hours and 45 minutes.
[00:57:56.360 --> 00:57:57.240] We're ready.
[00:57:55.120 --> 00:57:58.520] We can dive in.