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好的。
Okay.
所以，这里有一件事。
So here's something.
我们的节目宗旨。
Our show's motto.
没有太大的问题，也没有太小的问题，但有一些问题，我在这档节目中一直回避。
No question too big, no question too small, but there's some questions that I have on this show avoided.
我举个例子。
I'll give you an example.
GLP-1类药物。
GLP-1s.
搜索引擎几乎没怎么提及它们的存在，这倒也没关系，只是我读了很多关于它们的内容。
Search Engine has barely acknowledged their existence, which is fine, except I read a lot about them.
我经常思考它们。
I think a lot about them.
在我的私人生活中，我经常谈论它们。
And in my private life, I talk a lot about them.
但当GLP-1药物突然涌入美国文化时，我有很多问题，却不想在公众场合问出来。
But when they cannonballed into American culture, I had a lot of questions that I didn't wanna ask in public.
在2022年和2023年，对我而言，GLP-1实在是个太敏感的话题。
In 2022 and 2023, GLP-1s were just, for me, too hot a topic.
上网感觉就像走进了老西部酒馆里的一场疯狂枪战。
Going online felt like walking into a crazy shootout in an old Western saloon.
只不过那里没有枪手，全是火速开火的指责者。
Except instead of gunslingers, it was all fast draw scolders.
有人在网上指责名人使用GLP-1，但这些指责者又遭到其他人的谴责，因为他们在指责名人。
There were scolders out there scolding celebrities for taking GLP-1s, but then they were getting scolded by other scolders for scolding celebrities.
有些人因为服用药物却不够胖而被指责，甚至只是想减掉15磅就被批评。
Some people got scolded because they were taking the drugs despite not being fat enough, scolded for wanting to lose 15 pounds.
当然，富人到处被指责，被控抢走了真正需要这些药物的人的资源。
Rich people, of course, were getting scolded all over the place, accused of ripping GLP-1s out of the hands of the people who actually needed them.
这简直就是指责的混乱场面。
It was scolding mayhem.
与此同时，在现实生活中，我认识的人中有百分之二十减掉了15到40磅。
Meanwhile, offline, in real life, twenty percent of the people I knew just lost 15 to 40 pounds.
他们看起来很开心，而我有很多疑问。
They seemed happy, and I had questions.
我们到底对这些药物了解多少？
What did we really know about these drugs?
它们真的像宣称的那样帮助了人们吗？
Were they helping people the way they claimed to?
有什么副作用？
What were the side effects?
我有很多疑问，但我讨厌被指责。
I had questions, but I hate getting scolded.
所以我闭口不言。
So I kept my mouth shut.
与此同时，到了2026年，那些指责的人已经转向了其他话题，这些话题我会在2029年再讨论。
Meanwhile, in 2026, the scolders have moved on to other topics, topics I'll cover in 2029.
但今天，我们终于可以对这些令人着迷的药物获得一些答案了，原来它们比我们想象的还要古怪得多。
But today, we can finally get some answers on these fascinating drugs, which it turns out are much weirder than we ever knew.
所以这一周，我们将采访一位医生，她会从自己的角度讲述GLP-1药物的故事，这个视角非常独特，因为她服务的患者群体在媒体中几乎从不被提及，也完全缺席了早期关于这些药物的讨论。
So this week, we're going to talk to a doctor who's going to tell us the story of GLP-1s from her perspective, which is a very unique one because she's a doctor to a particular patient population that we don't hear from much in the media, almost never, and who were very absent from the entire early discourse around these drugs.
药物。
Drugs.
你能说一下你的名字和你的工作吗？
Can you say your name and what you do?
当然。
Sure.
我是拉凯尔·贝达德。
I'm Rachael Bedard.
我是一名医生，也是一名作家。
I'm a physician, and I'm a writer.
我是《纽约时报》意见版的特约撰稿人。
I'm a contributing writer to New York Times Opinion.
作为一名医生，我是一名内科医生，专长是老年医学和姑息治疗。
And as a doctor, I am an internist, and my subspecialties are geriatrics and palliative care.
但我有着一段不寻常的职业经历：六年里，我在里克斯岛担任医生，现在每周我会去一家无家可归者诊所工作几天。
But I've had this sort of unusual career where for six years, I was a physician on Rikers Island, and I now work in a homeless clinic a couple days a week.
你能跟我讲讲你在这家无家可归者诊所的工作吗？
Can you tell me about your work at that homeless clinic?
比如，诊所在哪里？
Like, where is the clinic?
那里是什么样子的？
What's it like?
你的工作是怎样的？
What's your work like?
这家诊所是市政府运营的一家安全网诊所。
So the clinic is it's a safety net clinic run by the city.
这座城市有一套嵌入公共医疗系统的安全网诊所网络。
The city has a network of these safety net clinics that are embedded in the public hospital system.
所以我的诊所位于布鲁克林的伍德豪尔医院。
And so my clinic is at Woodhall Hospital in Brooklyn.
诊所虽然设在医院内，但是一家提供初级护理的门诊诊所。
So the clinic's in the hospital, but it's an outpatient clinic with primary care.
我们服务的对象要么无家可归，要么处于不稳定的居住状况。
We serve people who are either unhoused or sort of in precarious housing situations.
他们最近可能刚获得住所，或者暂时借住在朋友的沙发上，类似的情况。
They were recently, you know, housed or they are staying on friends' couches or something like that.
但我们照顾的大多数人要么住在收容所，要么露宿街头。
But the majority of the people that we take care of are living in shelter or people who are sleeping on the streets.
所以我们提供他们所有的初级医疗服务。
So we do sort of all of their primary care.
这一群体患有共病精神健康问题的比例极高，共病成瘾问题的比例也很高，同时整体医疗状况也非常糟糕。
That population has a very high rate of comorbid mental health issues, very high rate of comorbid addiction issues, but also is just very medically sick.
所以我照顾的大多数人至少有一种慢性疾病，比如高血压、糖尿病或其他需要每天服药的疾病？
So the majority of folks that I take care of are have at least one chronic medical comorbidity, like high blood pressure or diabetes or other diseases like that for which they're taking daily medications?
我有很多问题，涉及很多不同的方向。
I have, like, a bunch of questions in a bunch of different directions.
其中一个问题是，你的工作让你接触到很多生活在纽约市的人。纽约的奇特之处——可能比美国其他地方更明显——是它有着极其明显的阶级分化。
One is it your work puts you I think a lot of people who live in New York City, the weird thing about New York, maybe more than other places in America, is that it's both incredibly class stratified.
你有非常精英、非常富有的人，也有工薪阶层和非常贫穷的人。
You have, like, very elite, very wealthy people, and you have working people, and you have very poor people.
但这些不同群体的人通常并不会真正相遇，除了可能在地铁里，或者就在街上。
But the people in those worlds don't always really run into each other besides maybe on the subway or literally on the street.
你过着一种不寻常的生活，一方面接触像《纽约时报》这样的高度精英世界，另一方面又与如此遥远的人群共事。
You have this unusual life where you're moving between, like, highly elite worlds, like The New York Times, and then working with populations that are so far removed from it.
而我认为，很多人为了在城市中生活下去，会选择在心理上屏蔽这些现实，但你却选择了一种无法回避的生活。
And I just wonder the thing that I think so many people block out in their minds in order to just live in a city, you've chosen to give yourself a life where you can't.
我只是想知道，这种生活是什么样的。
I'm just wondering what that's like.
是的。
Yeah.
所以，我要说的是，尽管纽约的不平等现象令人震惊，但我觉得纽约比像洛杉矶这样的城市有更多的社会交融，因为在洛杉矶人们总是开车出行。
So, you know, one thing I'll say about New York is although the rates of inequality here are astounding, there is, I think, actually more mixing in New York City than there is in a city like LA, for example, where people are always in their cars.
对吧？
Right?
比如，你在街道和地铁上都会与人互动。
Like, you are sort of interacting on the streets and on the subways, etcetera.
你知道的。
You know?
由于人口密集，人们彼此之间靠得更近。
And because of the density, people are just on top of each other much more.
所以，我的生活当然因为很多原因感觉极度分化，但我喜欢住在这里，因为在这里，人性似乎保持着一种连续性，而在国家其他地区或一些其他富裕城市，人们可能会完全与外界隔绝。
So it doesn't feel my life certainly feels extremely stratified for lots of reasons, but I think I like living here because it feels as though humanity is in continuity with itself in a way that in some other parts of the country or other very wealthy cities, you can be completely sort of cloistered off.
话虽如此，是的，我的临床工作不仅让我接触到，而且我认为与那些生活极其艰难的人建立了极其亲密的关系，而我的生活从未经历过这样的境遇，这让我对生活在这些境况中是什么样子有了不同的洞察。
That having been said, yes, my my clinical work puts me in not just contact with, but I think just in extremely intimate relationship with people whose lives are really, really difficult in ways that my life has never been and gives me a different sort of level of insight into what it's like to live in those circumstances.
对。
Right.
你能非常深入地看到与你自己截然不同的生活。
You get this very, very intimate view into lives that are very different from your own.
对。
Right.
比如，病人的天气体验和我的天气体验真的不同，因为他们暴露在自然环境中，而我却有更多保护自己的方式——比如他们来诊所时没有外套、没有手套，外面很冷，或者天气极热，他们却没有地方避暑。
Like, patients, their experience of the weather is really different than my experience of the weather because they are exposed to the elements in ways that I am not with fewer ways to protect themselves ranging from, like, they come to the clinic and they don't have a coat and they don't have gloves and it's really cold outside, or it's really hot outside and they don't necessarily have a place to take cover from that.
对吧？
Right?
所以，这是一种完全不同的方式去体验身体在相同空间中的存在，如果我能表达清楚的话。
And so, like, that's a really different way to be in a body in the same spaces that I'm in my body in, if that makes sense.
完全理解。
It completely makes sense.
你是怎么开始在收容所诊所工作的？
How did you end up working at the homeless clinic?
嗯，我当初选择学医是因为我想通过医学来做一些社会医学和社会正义方面的工作。
Well, I so I had gone into medicine because I wanted to do sort of social medicine, like social justice work through medicine.
但当时并不清楚具体该怎么实现。
And it wasn't totally obvious how to do that.
我很幸运地偶然得到了这份工作，参加了一个在赖克斯岛的进修项目，我的职责是照顾那些被关押在纽约市监狱系统中的老年人。
And I sort of very luckily, by chance, ended up in this job at a fellowship at Rikers where my job was to take care of older people who were incarcerated in the New York City jail system.
我非常喜欢这份工作。
And I loved that job so much.
在赖克斯岛当医生，日常是怎样的？
What does it look like day to day to be a doctor at Rikers?
赖克斯岛是个很特别的地方，因为它是一座岛，你知道的。
Rikers is a wild place because it is it's an it's an island, as you know.
实际上，我去过一次。
Once, actually.
哦，你去过？
Oh, have you?
是的。
Yeah.
但你应该描述一下，因为我认为大多数听众可能从未去过。
But you should describe it because I I'm a guess the median listener probably has not been.
是的。
Yeah.
所以里克ers岛是位于皇后区附近的一个岛屿。
So Rikers Island is an island off of Queens.
它通过一座长长的桥与皇后区相连。
It is connected to Queens via this long bridge.
桥的两端都有安检。
There are there's security at the front of the bridge and on the other side.
你只能开车进入这个岛。
You can only drive on the island.
你不被允许步行上岛。
You aren't allowed to walk on the island.
它是一个由纽约市矫正部门管理的独立堡垒。
It's sort of a fortress unto itself that the Department of Correction for New York City runs.
它是一个由多个监狱组成的综合体，全都位于这个岛上，包含许多不同的建筑。
And it is a complex of multiple jails that are all on this island, a bunch of different buildings.
这些建筑收容着不同特殊群体的人群。
The buildings house people sort of in different set of special populations.
有一座是专门关押女性的。
There's one for women.
有一座是关押身体状况较差的人的。
There's one for people who are sicker.
还有专门用于精神健康护理的单元。
There are ones for specialized mental health units.
根据你所从事的医学领域，你的日常工作可能会非常不同。
And depending on the kind of medicine you practice, your day can look very different.
因此，在我刚在那里工作的前几年，我会打印一份系统中所有65岁以上人员的名单，然后去寻找他们所在的位置，把他们叫到该建筑内的诊所。
So for the first few years that I worked there, I would basically print a list of everybody in the system who is older than 65, and I would go sort of try to find those people where they were and call them down to a clinic in that building.
纽约市监狱系统中没有行动自由，这意味着每个人从一个地方转移到另一个地方时，都必须有狱警陪同。
There's no freedom of movement in the New York City jail system, which means that every time a guy moves from one place to another, he has to be accompanied by an officer.
比如，必须有人来接他，打开门，带他出来，然后送他到你这里。
Like, somebody has to come pick him up and unlock a door and take him out and bring him to you.
所以事情进展得非常缓慢。
So things move very slowly.
就像一直待在机场一样。
Like, it's like being in the airport all the time.
对吧？
Right?
急诊室是一个极其拥挤的系统，需要大量的人际接触。
Or the emergency room is an incredibly sort of congested system that requires a huge amount of excess human contact.
由于安全原因，你永远不可能真正关上门，因此在临床接触中很难拥有真正的隐私。
It's hard to have real privacy during clinical encounters because you're not actually sort of behind a truly closed door ever for safety reasons.
但你可以想象，要在这种环境中为那些对自我暴露感到犹豫的人提供护理，这其中存在着一种张力。
But you can imagine that there's, like, a tension there with being able to provide care to people who are ambivalent about revealing themselves in that kind of environment.
对吧？
Right?
因此，这种临床互动深受系统安全顾虑的制约。
And so it is a clinical dynamic that's very much constrained by the security concerns of the system.
其中一些安全顾虑确实有充分理由，但有些则不然。
And some of those security concerns are really well justified and some aren't.
我接待的第一个病人患有晚期癌症。
One of the first patients I had was with advanced cancer.
我去医院探望他时，他正被监禁在医院里。
I went to visit him while he was in the hospital incarcerated.
一名狱警坐在他房间外。
There was a corrections officer sitting outside his room.
这位病人告诉我，他非常喜欢彩虹糖。
He had told me he really liked Skittles, the patient.
我带了彩虹糖去。
I brought Skittles.
我必须打开包，让警卫查看包里有什么，才能被允许进入房间。
I had to open my bag and show the officer what was in my bag before I was allowed in the room.
我当时太年轻，不懂得该装作淡定，结果我说我给他带了彩虹糖。
And I was too sort of junior to know that I should play it cool, and I said I brought him Skittles.
那人说，他不准吃这个。
And the guy said, he's not allowed to have those.
我就问，为什么？
And I said, why?
他回答说，因为彩虹糖不在监狱小卖部的清单上。
And he said, well, Skittles aren't on commissary.
所以他不能拥有任何不在监狱小卖部清单上的东西。
So he's not allowed to have things that aren't on commissary.
这显然根本不是什么真正的安全顾虑。
That's, like, obviously not a real security concern.
对吧？
Right?
这只是一个规定。
That's just a rule.
是的。
Yeah.
这并不是法律，你知道的，尽管跟我说这话的人穿着制服。
And that's not a law, you know, even though the guy saying it to me is in a uniform.
制服。
Uniform.
我当时就想，我要把那些彩虹糖给他。
And And I I was was like, like, I'm I'm gonna gonna give him the Skittles.
你知道吗？
You know?
你能想象，要做到这一点有多难，你必须真正得到医疗管理方的支持，才能有底气这样运用自己的判断。
And you can imagine that that's hard to do, and you have to have, like, a fair amount you have to really feel empowered by the folks who run the health care side of things to be able to use your judgment like that.
我很幸运，我的上司们都很开明。
And I was super lucky in who my bosses were.
我当时在疫情期间在那里工作。
I was there for COVID.
那真的太疯狂了。
That was really wild.
这让我和我的许多同事以及上司之间产生了深厚的情感联系。
It made me feel incredibly bonded to a bunch of my colleagues and the my supervisors.
然后我在2022年离开时已经精疲力尽了。
And then I left at the 2022 quite burnt out.
和我在里克斯岛一起工作的一群人后来去了伍德霍尔工作。
And a bunch of people who I worked with at Rikers moved on to work at Woodhall.
就像《广告狂人》里他们重新设计毛皮那一幕一样。
And it was like, you know, like in Mad Men when they, like, remake the fur.
你明白我的意思吗？
You know what I mean?
他们说，第三季我们要
They're they're they're like, season three, we're doing
一个新的。
a new one.
就像是，
That's, like,
是同样的人。
the same guys.
那就是当时的情况。
That was that is what it was like.
我们在伍德霍尔搞起了《广告狂人》那一套，那是一群我在里克斯时特别喜欢共事、充满使命感的人。
We'd, like, mad men'd up at Woodhall, which is a bunch of people who I loved working with at Rikers who are super mission driven.
所以我就这样去了那里。
And so that's how I ended up there.
那你现在在那里，听起来我和你共事的那些人有很多共同点。
And so you're there now, and it sounds like the thing that I mean, there are many things in common, the people you're working with in common.
但另一个共同点是，我觉得普通人一想到医生，就会觉得是那种你去看病，他们帮你找出问题所在，然后给你开药的人。
But the other thing that sounds shared is that I think when a layman thinks about a doctor, it's a person you go to, and they figure out what's wrong with you, they give you medicine.
你对医疗护理的体验是，很多时候，工作不仅关乎治疗身体，更关乎人们周围的社交结构。
And your experience of medical care is that oftentimes the job is as much about the social structures around people as just, like, treating their bodies.
因为发生在他们身体上的事情和他们所处的社交结构是密不可分的。
Because the things that are happening to their bodies and the social structures they're enmeshed in are so inseparable.
是的。
Yes.
不过我会说，这对任何医疗环境、任何患者群体都真正适用。
Although I would say that's truly true for any any practice environment, any patient population.
真的吗？
Really?
就是这么回事。
It's just yeah.
只是挑战确实不同，而且在我看来，我的患者群体中这种情况更明显。
It's just the challenges are really different, and it's more visible, I think, with my patient population.
但如果你自费去看私人医生，在纽约，这种初级医疗的层级分化和获取机会简直惊人。
But if you are paying out of pocket to see a concierge doctor, which in New York, there's, like, this incredible stratification and access to primary care.
在高端层面，人们自费聘请私人医生，这意味着他们支付巨额费用，让医生随时待命为他们服务。
And one, at the high end, people are paying out of pocket to see concierge doctors, which means that they're paying some huge amount of money to have this person basically be on call to see them.
这种关系的动态完全由支付模式、个人的社会经济地位、能否获得其他专科医生的护理，以及他们是否能负担医生建议的治疗（比如医生说你这背痛需要按摩，而这个人能付得起按摩费）决定。
And the dynamics of that relationship are totally determined by that payment model, by that person's socioeconomic status, by their access to be able to get care from other kinds of specialists, by their ability to like, you know, that doctor says maybe you need a massage for this back pain, and the person can pay for that massage.
对吧？
Right?
没错。
Right.
几乎不可能把身体和社会因素分开。
It's sort of impossible to separate the body from the social.
是的。
Yeah.
是的。
Yeah.
是的。
Yeah.
而这尤其明显。
And that's just particularly visible.
我的病人的社会环境如此艰难，制造了重重障碍，让他们无法像我们希望的那样照顾好自己的身体，因此医生所做的很多工作，其实是代表我的病人与这个世界进行协商，为他们争取我认为他们需要的东西。
And the social sort of circumstances for my patients are just so particularly crushing and throwing up obstacles so they're being able to take care of their bodies the way that we would want them to, that a lot of what the doctor ends up doing is sort of negotiating with the world on behalf of my patients to get them things I think they need.
我还想说的是，因为我的患者群体，健康在很大程度上是由社会因素决定的。
The other thing I would say is that because my patient population, you know, health is socially determined up to a large degree.
所以，当你描述去看医生，你说自己哪里不舒服，医生就给你开药，你想到的可能是像链球菌性咽喉炎之类的情况。
So, like, when you describe, like, you go to the doctor, you say something's wrong with you and they give you a medicine, you're picturing going for, like, strep throat or something.
对吧？
Right?
是的。
Yeah.
或者我得了流感，想要达菲，因为那是健康人群的体验。
Or I have the flu and I want Tamiflu because that's the experience of people who aren't sick.
但我的患者群体一直生病，他们始终与疾病共存。
But my patient population is sick, so they are living with illness all the time.
当他们来找我时，他们带来的往往不是新的症状，而是我们一直在努力调整他们对慢性疾病的体验。
And when they are coming to me, they're not coming necessarily with a new complaint so much as we are in this constant process of trying to modify their experience of illnesses that they live with chronically.
你所描述的这一切，完全不符合我之前对你们所治疗人群的片面刻板印象，比如我脑海中关于司美格鲁肽使用者的流行文化刻板画面。
There's nothing about anything you've described where my under informed stereotypical view of the world you're treating would say, like, this is the pop culture sketch I have been given of Ozempic users.
你能告诉我，你第一次听说GLP-1类药物是什么时候吗？
Can you just tell me the first time you heard about GLP-1s?
它们是什么时候进入你的视野的？
Like, when did they show up on your radar?
是的。
Yes.
没错。
So right.
正是如此。
Exactly.
而这在很大程度上正是我对这些药物产生兴趣的全部原因。
And this is sort of my whole interest in these medicines to a large degree.
GLP-1类药物已经存在很长时间了。
So GLP-1s have been around for a really long time.
实际上，某种形式的GLP-1药物已经出现了将近二十年。
Like, some version of GLP-1s have been around for almost twenty years.
曾经有过第一代GLP-1药物，仅用于糖尿病患者。
There were sort of, like, first generation GLP-one medications that were only used for diabetics.
所以我早就知道这些药物了。
So I've known about those medicines for a really long time.
但像奥兹姆皮克这一代以及之后出现的GLP-1类药物，真正进入大众视野是在2021年、2022年左右。
But the sort of GLP-1s class that is, like, the Ozempic generation and then everything that's followed really came on the radar, like, 2021, 2022.
我觉得我第一次开始关注它们，是因为我在主流媒体上读到相关报道，而不是在医学文献里。
And I think the first time I sort of started paying attention to them was when I read about them in mainstream media, not in medical literature.
嗯。
Mhmm.
尤其是最初那几个月，这些药物根本无法获得
Because especially, like, those very early months, like, they weren't accessible
极其容易获得。
Extremely accessible.
因此，诺和诺德公司进行了一些研究，显示这些药物对糖尿病患者有惊人的效果。
And so there were sort of these studies that had been done, you know, by Novo Nordisk suggesting, like, incredible results for diabetic patients.
但总有大量新药不断被研发出来，虽然前景很好，却太过昂贵，根本不会被列入我患者的用药目录，所以我对它们其实了解不多。
But there are lots of medicines that are being invented all the time that are really promising but that are too expensive and are just, like, not gonna be on formulary for my patients that I don't actually know that much about.
我个人对GLP-1药物产生浓厚兴趣，其实是认识的一个在《Vogue》工作的人给我打电话，问我：这到底怎么回事？
I think the the way that I personally got really interested in the GLP-1s was I actually think that somebody I know who worked at Vogue called called me called me and was like, what's the deal?
你知道的吗？
You know?
我认识的每个人都在想要这种药。
Like, everyone I know wants this medicine.
这药到底有什么特别的？
Like, what's the deal with this medicine?
我当时就说：这不就是治疗糖尿病的药吗？
And I was like, the diabetes drug?
说实话，当时我根本没注意到它。
Like, know, it was sort of not on my radar.
后来，随着减重效果变得清晰和广为人知，这种药物开始被非糖尿病患者追捧，他们想用它来减肥。
And then I started to be interested in it as the weight loss effects became clear, well known, and then the drug started to be sought by a patient population that didn't have diabetes but that wanted to use it for weight loss.
它逐渐变成了一种文化现象。
And it became sort of this, like, cultural phenomenon.
我觉得2022年到2023年才是真正发生这一切的时候。
Like, I think 2022, 2023 is really when that happened.
对我来说，2023年是‘Ozempic第一人称故事’横空出世的一年。
Like, 2023 is the year to me of the Ozempic first person essay.
是的。
Yes.
2022年对我来说，是人们私下悄悄谈论它的一年。
2022 was the year for me of people whispering about it.
没错。
Right.
是的。
Yeah.
然后2023年，人们就开始说：好吧。
And then 2023 was people being like, alright.
我试过了。
I did it.
我尝试了。
I tried it.
或者，这对身体积极性运动意味着什么？或者其他什么？
Or, like or what does it mean for the body positivity movement that this is happening or whatever?
对吧？
Like, right?
这真是件很有趣的事，一种糖尿病药物变成了别的东西。
It was this really interesting thing where this diabetes medicine became this other thing.
到了那个时候，真的很有争议。
And at that point, like, really controversial.
对吧？
Right?
最初是一种药物，同时也成为了一个讨论对象。
Initially was a medicine that was also a discourse object.
对。
Right.
没错。
Exactly.
没错。
Exactly.
它打乱了所有那些关于身体积极运动的相对固定的立场和观念，正如你所说。
And it, like, scrambled all these there were so many relatively set battle lines and ideas about, as you said, like, body positivity.
然后出现了这么一个东西，直接把这张桌子狠狠地、狠狠地、狠狠地摇晃了一番。
And then you had this thing which just it took this table and just, like, shook it really, really, really hard.
完全没错。
Totally.
而且这真的出人意料，老实说。
And it was so unexpected, frankly.
对吧？
Right?
因为在这一类药物出现之前，一个普遍的认知是我们没有能让人减肥的神奇药丸。
Because one of the sort of truisms up until this class of medicines was we didn't have a magic pill for weight loss.
对吧？
Right?
在九十年代，像芬芬这样的药物曾引发过热潮，那时总有一些被热议的药物，号称能让人神奇地减掉体重。
That there had been sort of all of these prior cultural moments like fen fen in the nineties, where there had been, like, a hot discourse object medicine to help people magically shed pounds.
在GLP-1类药物之前，没有任何药物被证明足够安全，可以作为长期干预手段。
Nothing prior to GLP-1s had been proven safe in a way that it could be sort of a sustained intervention for people.
之前几乎没有真正有效的药物。
Nothing really worked that well.
但突然之间，很多人都开始使用司美格鲁肽。
Whereas, like, all of a sudden, people were taking Ozempic.
它们看起来是安全的。
They it seemed safe.
人们能够很好地耐受，而且在五周内减掉了十五磅。
They were tolerating it okay, and they were losing 15 pounds in five weeks.
它的疗效如此前所未有。
And that it was just so unprecedented in its efficacy.
我们以前从未有过这样的东西。
Like, we hadn't had anything like that before.
我的意思是，到2023年，我们知道这些药物能降低全因死亡率。
I mean, like, these drugs, by the 2023, we knew that they had an all cause mortality benefit.
作为治疗效果来说，这简直难以置信。
Like, that's unbelievable as an outcome.
在医学领域，很少有药物能在短短用药期内证明能预防人死亡。
There are very few things in medicine where you can show that it prevents people from dying over a very short period of time of taking the drug.
而这种药物做到了。
And this did that.
因此，从医学角度来看，这真的非常了不起，令人无比兴奋。
And so, like, it was really an incredible from a medical perspective, it was super exciting.
但与此同时，还存在着一种关于减肥、身材形象之类的讨论，完全脱离了这些药物实际的医疗影响。
And at the same time, there was this, like, weight loss, body image, yada yada discourse that was totally divorced from the actual medical impacts of the drugs.
贝达德医生所指的这种‘等等之类的’讨论，正是我在本集开头提到的——那段时间涌现了大量作家的文章，他们公开质疑这些新药是否在道德上是错误的。
This yada yada discourse doctor Bedard's referring to, that's what I was referencing in the beginning of this episode, a season which yielded many essays from writers wondering out loud if these new drugs were just morally wrong.
对贝达德医生而言，这些问题文章的症结在于，它们几乎从未认真探讨过作家自身、社交圈以及Instagram上的名人之外的世界。
To doctor Bedard, the problem with these pieces is that they rarely seriously engaged with a world beyond the writer, their social circle, and celebrities on Instagram.
我在多个层面上都感到不满。
I was annoyed on a bunch of different levels.
其中一个问题是，这种关于身体、甚至疾病和医学的文化讨论，几乎从不反映真正患病者的真实体验。
One thing is that it just highlighted how much cultural discourse about bodies, even illness, medicine, people's experience of their bodies, really almost never reflects the experience of people who are actually ill.
你知道，2型糖尿病是美国人最普遍的慢性病之一。
So, you know, type two diabetes is, like, one of the most common chronic conditions that Americans live with.
它真的可能非常糟糕。
It's really can be really terrible.
对吧？
Right?
像这样，这个国家有数百万人因为糖尿病严重到出现血管并发症，导致肢体血流中断，不得不截肢。
Like, millions of people in this country have had a limb amputated because their diabetes was sufficiently bad that they had vascular complications where they stopped getting blood flow to a limb, and they had to lose a leg.
你知道吗？
You know?
这真的很糟糕。
That's really terrible.
在美国，有五十万人正在接受透析，这意味着他们每周三次，每次数小时，坐在一间满是坐着轮椅、连接着大型静脉导管的人的房间里，通过这种像血液清洗机一样的透析机进行血液净化。
There are half a million people in The US who are on dialysis, which means that three times a week, they go for several hours and sit in a recliner in a room full of people in recliners hooked up to huge IV catheters that are exchanging their blood through this, like, blood washing machine, dialysis machine.
这种生活方式真是难以想象。
That's a wild way to live.
对吧？
Right?
想象一下，如果你必须这样生活。
Imagine if you had to do that.
这些经历在主流媒体关于疾病的第一人称叙述中从未得到反映。
And those experiences are never reflected in first person writing about illness in the mainstream media.
我认为，像我平时阅读的新闻和休闲类出版物中，几乎从不真正描述这些情况。
They're almost never actually described, I think, in, you know, the publications that, like, I read both for news and pleasure.
而我今年43岁了。
Whereas, I'm 43.
据我记忆所及，我一直每周读到一篇关于一位白人女性对自己体重感到不安的散文。
I think for as long as I can remember, I have been reading an essay a week about what it's like to be a white lady who doesn't feel great about her weight.
这种状况在我的生活中始终如一，尽管世界发生了许多变化。
That that is a constant in my life through many changes in the world.
而最让我感到恼火的是，这种有望彻底改变美国疾病人群健康状况、甚至可能改变美国人预期死亡率的突破性药物，却全都被导向了同样的讨论框架，并且用我一生都在阅读的那些焦虑和神经质主题来解读。
And the idea that this breakthrough class of medications that had the potential to revolutionize, like, disease population health in The US potentially change the expected mortality for Americans, like, that it was all sort of being funneled into this same discourse and also processed using the same types of anxieties and neuroses that were sort of the themes that I've been reading about my whole life, like, was really annoying to me.
对贝达德医生来说，2023年令人恼火的是，关于这些药物的讨论几乎把所有关注都放在了它们的美容属性上。
To doctor Bedard, what was annoying in 2023 was how the conversation about these drugs gave almost all of its oxygen to their cosmetic attributes.
当瘦身现在比以往更容易用钱买到时，这对每个人的身材形象意味着什么？
What did it mean for everybody's body image that thinness was now much easier to buy than it had been before?
即使现在说出这句话，我都能感受到它引发的所有争论所带来的热度与激动。
I can feel, even now saying that sentence, the heat and excitement of all the arguments it provokes.
但对于贝达尔医生来说。
But for Doctor.
贝达尔医生觉得这些争论让她想对着屏幕大喊。
Bedard, those arguments made her want to yell at the screen.
哪怕只是一瞬间，也别再考虑那些美容方面的含义。
Forget, even for a second, the cosmetic implications.
GLP-1类药物正在改变她一些最脆弱病人的生活。
GLP-1s were transforming the lives of some of her most vulnerable patients.
她认为，讨论中应该有更多关注点放在这些方面，而对话绝不能如此聚焦于媒体精英们极其特定的生活。
She thought more of the oxygen in the conversation should have gone there, and that the discourse certainly should not have been so focused on the very particular lives of media elites.
我们稍作短暂休息。
We're gonna take a short break.
回来后，我们将脱离当前的讨论，远离昨天互联网上的对话，转向今天。
When we come back, we are going to move away from discourse, away from the conversations of yesterday's Internet to today.
GLP-1药物背后的真正科学，以及医生们在过去三年广泛使用过程中发现的种种奇特现象。
The actual science behind GLP-1s and all the weird things doctors have been learning about them in their last three years of widespread deployment.
我是凯瑟琳·尼古拉伊，我帮助全球数百万人改善睡眠，安抚神经系统，让他们在思绪停不下来时能够安静下来。
I'm Catherine Nikolai, and I help millions of people around the world sleep better, rest their nervous systems, and shut their brains off when they won't stop spinning.
在我的播客里，什么大事都不会发生。
On my podcast, nothing much happens.
我讲述的是温馨、平静的故事，从不会有任何戏剧性的情节。
I tell cozy, calming stories where nothing dramatic ever happens.
只有柔和的旁白、细腻的感官细节，以及温和的重复，专为让你入眠而设计。
Just soft narration, sensory detail, and gentle repetition designed to lull you to sleep.
没有需要跟随的情节，没有需要解开的谜题，只有宁静。
There's no plot to follow, nothing to figure out, just peace.
在您收听播客的任何平台都可以收听《什么都没发生》。
Listen to Nothing Much Happens wherever you get your podcasts.
你好，搜索引擎的听众们。
Hello, search engine listeners.
我今天来跟你们聊聊一档我超爱的播客。
I am here to tell you about a podcast I love.
它叫《This American Life》。
It's called This American Life.
由伊拉·格拉斯和他的团队制作，他们是音频领域最顶尖的制作人之一。
It's hosted by Ira Glass and his team of some of the best producers in audio.
每周，他们会选定一个主题，为你带来一系列关于该主题的故事，这些故事或幽默、或感人、或宏大、或微小，但最重要的是，它们都是真实的。
Each week, they choose a theme and bring you a variety of stories on that theme, stories that are funny, moving, big, small, but above all, true.
我曾经真的会把《This American Life》的CDR刻录下来，然后在从费城到蒙特利尔再往返的十四小时车程中，连续不断地听上十四小时的节目。
I literally used to burn the CDRs of This American Life, and then on my fourteen hour drives from Philadelphia to Montreal and back, I would just listen to fourteen hours of the show back to back to back to back.
我觉得我听过的《This American Life》比其他任何媒体内容都多。
I think I've listened to more of This American Life than I've listened to almost any other piece of media.
正是在这里，我爱上了音频。
It's where I learned to love audio.
正是在这里，我学会了我如今所从事的这份工作。
It's where I learned to do the thing that I do.
这个节目如此受欢迎，以至于推荐别人去听它，感觉就像建议人们去享受暑假一样，但我还是这么做，因为这个节目完全可以和暑假一较高下。
It's also such a beloved show that it feels a little bit like recommending people try summer vacation, but I'm doing it anyway because this show competes with summer vacation.
请去听听看。
Please check it out.
如果你是那种通过搜索引擎找内容的听众，却还没听过《This American Life》，那我很高兴能带来这个好消息。
If you're a search engine listener who somehow has not heard This American Life, I'm very happy to be the bearer of good news.
请去收听，并告诉他们是我们推荐你的。
Please go listen and tell them we sent you.
欢迎回到节目。
Welcome back to the show.
所以你能告诉我，GLP-1在你体内到底在做什么吗？
So can you tell me literally just, like, what are GLP-1s doing inside of your body?
这些药物发挥作用的机制究竟是怎样的？
Like, what are the mechanics of how these drugs work?
好的。
Okay.
当我们谈论GLP-1这一类药物时，我们指的是这一类药物。
So when we're talking about GLP-1s as a class, we're talking about this class of medications.
第一个这类药物实际上是在2005年推出的。
The first one actually came out in 2005.
但目前流行的讨论主要指的是过去几年里推出的那些药物。
But, like, this popular conversation is referring to the ones that have come out in the last couple of years.
其中第一个是司美格鲁肽，也就是 Ozempic 或 Wegovy。
And the sort of first one is semaglutide, which is Ozempic or Wegovy.
第二个已经获批并上市几年的药物是替尔泊肽，也就是 Zepbound 或 Mounjaro。
Then the second one that's already approved and been on the market for a couple years is tirzepatide, which is Zepbound or Mounjaro.
还有一种正在研发中的药物，我简直没法念出来，就是那个以
And then there's this one in the pipeline that I literally cannot pronounce, the one with the
r.
r.
Redistrutide。
Redistrutide.
Redistrutide 这名字简直糟透了。
Redistrutide is, like, the worst possible name.
是的。
Yes.
我根本拼不出来。
Like, I can't spell it.
我也念不出来。
I can't say it.
所以 semaglutide 是一种 GLP-1 受体激动剂的肽类物质。
So semaglutide is this peptide that is a GLP-one agonist.
激动剂。
Agonist.
激动剂的意思是，它是一种能与体内 GLP-1 受体结合的肽。
An agonist means that it's a peptide that binds to the GLP-one receptor in the body.
而体内的 GLP-1 会发挥几种不同的作用。
And GLP-one in the body does a couple of different things.
它减缓胃排空，让你的胃保持饱腹感更长时间。
It slows gastric emptying, so it makes your stomach stay full longer.
不只是那种饱腹的感觉，而是真的，比如我吃了一沙拉，它就会一直留在那里。
Like, not the feeling not just the feeling of being full, but literally, like, if I eat a salad, it stays there.
没错。
Exactly.
这确实会增加你的饱腹感，并让你更快感到饱足。
That does absolutely increase your fullness and gets you to fullness faster.
是的。
Yeah.
它还通过作用于大脑中的激素受体来增强饱腹感，减少饥饿感并增加饱足感。
It also does increase your sense of fullness by working on, like, hormone receptors in the brain, and it decreases hunger and increases satiety.
而且这正是它在糖尿病治疗中如此重要且有效的原因。
And then it and this is why it's really important and works in diabetes.
它调节血糖平衡，促使胰腺在血糖水平升高时释放胰岛素。
It works on glucose balance, and so it provokes the pancreas to release insulin in response to high glucose levels.
所以它并不会让胰腺随意地持续释放胰岛素，而是会增强身体在血糖升高时对胰岛素的反应。
So it doesn't cause your pancreas to just, like, willy nilly release insulin all the time, but it augments the insulin response to high glucose levels in your body.
当我去吃糖、面包之类的东西时，葡萄糖进入我的身体，这两者之间是什么关系？
And what's the relationship between like, glucose enters my body when I eat, like, sugar or bread or something like that.
葡萄糖和胰岛素之间有什么关系？
What's the relationship between glucose and insulin?
当你摄入任何含有碳水化合物的食物时，它们会被分解，释放出葡萄糖——也就是糖分——进入血液。
So when you eat anything that has carbohydrates in it, it gets broken down to release glucose, which is like sugar, in your blood.
当血液中出现葡萄糖时，位于腹部后方的胰腺就会释放胰岛素，这是一种激素。
In response to glucose in the blood, the pancreas, which is like an organ in the back of your belly, releases insulin, which is a hormone.
胰岛素帮助你的肌肉将血液中的葡萄糖吸收进去，并转化为能量。
Insulin helps your muscles take the glucose out of your blood into the muscle and use it for energy.
二型糖尿病或糖尿病前期患者会发展出胰岛素抵抗，这意味着他们对胰岛素的反应减弱，因此更难将血液中的葡萄糖清除掉。
What happens in people of type two diabetes or people of prediabetes is they develop insulin resistance, which means that they have decreased response to insulin, which means they are less effective at taking the glucose out of your blood.
这意味着，为了把葡萄糖从血液中清除，身体需要释放更多的胰岛素。
And that means that your body needs to release more insulin in order to take that glucose out of your blood.
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是的
Yeah.
因此，对于经常血液中葡萄糖水平非常高（称为高血糖）的糖尿病患者来说，这会引发一系列下游影响。
So for diabetics who often have very high levels of glucose just like circulating in the blood, high levels of glucose called hyperglycemia, it has all sorts of downstream effects.
它会损害你的眼睛。
It hurts your eyes.
它会损害你的肾脏。
It hurts your kidneys.
最终，它会导致动脉中斑块堆积，从而引发心脏病发作和中风。
Eventually, it contributes to plaque buildup in your arteries, which can cause heart attacks and strokes.
因此，对于糖尿病患者，你需要降低他们的葡萄糖水平，即降低血液中平均循环的葡萄糖水平。
So what you want to do in diabetics is get their glucose levels, their average circulating glucose levels down.
GLP-1受体激动剂通过在你出现葡萄糖激增时向胰腺发出信号，促使胰岛素释放，从而防止葡萄糖水平飙升过高。
And GLP-one agonists help do that by signaling to your pancreas when you have a glucose spike to release insulin so that the glucose spike doesn't spike too high.
基本上，它有助于将你的血糖水平维持在身体能够应对的范围内。
Basically, it helps sort of maintain your glucose levels within a range that your body can handle.
GLP-1受体激动剂通过这些综合效应，比如司美格鲁肽（Wegovy和Ozempic），能导致10%到15%的体重下降，是的。
And GLP-one agonists, through that sort of combination of effects, the semaglutide, like, Wegovy Ozempic lead to, like, 10 to 15% body weight loss Yeah.
在研究中，这一效果持续了一年。
Over the course of a year in the studies.
但我觉得这些药物真正有趣的地方，也是它们引发如此多关注的原因，是它们在初期试验中展现出的预期效果——改善血糖控制和减重。
But the thing that I think is really interesting about these drugs, and one of the reasons that they've inspired so much excitement, is because they've had effects that we sort of anticipated that were, like, targeted effects in the initial trials, improved blood sugar control and weight loss.
此外，它们还带来了一系列意想不到的下游效应，这些效应很可能与体重减轻和血糖控制改善有关。
And then they've had a bunch of unexpected downstream effects probably related to weight loss and better blood sugar control.
比如，它们能预防心脏病发作。
Like, they prevent heart attacks.
它们能预防中风。
They prevent strokes.
它们能阻止患者发展为糖尿病肾病。
They prevent people from progressing to diabetic kidney disease.
它们似乎还能改善人们的膝关节炎，这一点真的出乎意料。
They seem to improve people's knee arthritis, which, like, was really unexpected.
它们似乎能改善心力衰竭。
They seem to improve heart failure.
而且它们还可能对成瘾产生影响。
And then they also have this potential effect around addiction.
这很有趣，因为你无法将这种影响归因于减重。
And that's interesting because you really can't attribute that impact to weight loss.
所以，就像是
So, like, it's
我没有理由认为，如果我体重225磅或180磅，就应该多喝或少喝酒。
There's no reason to think that if I'm two hundred twenty five pounds or a hundred eighty pounds, I should want to drink more or less.
对。
Right.
没错。
Exactly.
除非可能有一些心理影响之类的。
Other than maybe there's some psychological impact, etcetera, etcetera.
但我们真正感兴趣的是，研究发现GLP-1受体存在于一些我们之前并未充分认识到其存在、也未完全理解其在我们未曾考虑的领域中可能发挥的作用的地方。
But what we're sort of interested in is it's revealed that there are GLP-one receptors in places where I think we didn't totally recognize they were there, didn't fully recognize their potential role in things that we weren't thinking about.
因此，你的大脑中多巴胺奖赏回路里也存在GLP-1受体。
So there are GLP-one receptors in, like, the dopamine reward circuitry in your brain.
关于成瘾机制的一个主要假说是：GLP-1激动剂在这些区域结合后，会干扰奖赏回路的信号通路，尤其对那些已形成强烈奖赏通路、与成瘾行为紧密关联的人而言，这种干扰尤为明显。
And one sort of hypothesis around the addiction stuff or the sort of strongest hypothesis is that GLP-one agonist binding there is interrupting reward circuitry pathway stuff in a way that for people who have strong reward pathways built around addictive behaviors, like, interrupts that.
这些出人意料的正面效果——即超出单纯减重预期收益的额外效应——是否暗示着，某种程度的超重可能比我们之前理解的对健康更具危害？还是说，这些药物只是在我们尚未理解的部位发挥了作用？
And is it like these sort of unexpected positive effects, the ones that are sort of surplus effects that go beyond what you would have modeled as likely benefits of just, like, losing weight, does it suggest that maybe being, like, a certain amount of overweight can be more dangerous to our health than we understood, or is it more like these things are just doing things in places that we don't understand?
我认为是前者。
I think it's the first.
我认为，GLP-1药物展现出的多样化作用非常有趣，这表明肥胖——长期以来，肥胖研究者一直认为——是一种病理状态，其影响远不止体重增加和身体变大这么简单。
I think that one of the things that's really interesting about the diverse array of effects that the GLP-one drug seem to have is that it suggests about the fact that obesity, in which people who study obesity have long asserted, is a pathological condition that has consequences way beyond just being overweight and moving around the world in a bigger body.
体内过多的脂肪组织会改变身体内多种激素信号传导和稳态机制。
Having a lot of excess fat tissue on your body changes all sorts of hormone signaling and homeostasis mechanisms in your body.
因此，减少这些脂肪组织，会显著改变身体的自我调节能力。
So losing that adipose tissue, that fat tissue, makes a huge difference in changing how your body self regulates.
这似乎改善了我们可能完全没有预料到的许多方面。
And that seems to improve a whole bunch of things that we maybe didn't totally anticipate.
有一种模糊的说法是，GLP-1会减少炎症，这确实是事实。
There's this sort of hand wavy thing that the GLP-1s decrease inflammation, which is true.
我们确实知道，它们能降低体内的炎症标志物。
We sort of do know that, that they decrease inflammatory markers in the body.
看到减少炎症对人们有这么多不同的益处，真的非常有趣。
And just seeing all the different ways in which decreasing inflammation seems to help people is really fascinating.
是的。
Yeah.
你已经描述了已知的好处。
You've described the known benefits.
你提到还有一些，嗯，我不想说是未知的潜在益处，但确实有一些看起来不错的问号式现象。
You described that there's some, like, sort of I don't wanna say unknown possible benefits, but, like, question mark y things that look good.
有成千上万种看起来不错但还带着问号的现象。
A million things that are, like, question mark y things that look good.
我应该列一些出来，因为太令人兴奋了。
Like, I should just list some of them because it's so exciting.
癌症预防。
Cancer prevention.
我们知道，另一方面，肥胖是多种癌症的风险因素。
So we know this is another one where, like, on the one hand, we know that there are a bunch of cancers for which obesity is a risk factor.
乳腺癌就是其中之一。
Breast cancer is like that.
结肠癌也是如此。
Colon cancer is like that.
GLP-1似乎对这些癌症有帮助。
GLP-one seem to help with those.
还有一些癌症，我们并不认为肥胖是其风险因素，但GLP-1由于其抗炎作用，可能也发挥作用，这一点我们还不完全确定。
There are a bunch of cancers where we don't think of obesity as being a risk factor, where GLP-1s, because of this anti inflammatory sort of impact, we're not totally sure, may also play a role.
因此，目前有一些试验正在研究癌症预防。
So there are trials to look at cancer prevention.
目前正在进行针对阿尔茨海默病预防的临床试验。
There are trials to look at Alzheimer's prevention.
首个阿尔茨海默病预防试验结果为阴性，也就是说，这种药物没有产生明显效果。
The first Alzheimer's prevention trial was negative, which means, like, the drug didn't make a difference.
但我并不认为这能最终证明它对阿尔茨海默病的预防或治疗完全没有帮助。
But I don't think it's conclusively negative that it doesn't help with Alzheimer's prevention or treatment necessarily.
这方面还需要开展更多试验。
There's sort of more trials to be done there.
目前在帕金森病领域也有相关临床试验正在进行。
There are trials happening in Parkinson's disease.
这些是重大且极为常见的疾病，要么导致死亡，要么彻底摧毁人们的生活。
Like, these are big, extremely common conditions that that either lead to death or that totally derail people's lives.
是的。
Yeah.
因此，那些尚未充分研究或尚未被证实的潜在益处依然令人无比振奋。
And so the potential benefits that are still undercharacterized or unproven are super exciting.
那么，你们目前正在追踪哪些目前未知或存疑的潜在危害呢？
And are what are the current unknown or questionable possible harms that you're tracking?
我的意思是，有一个方面已经有一些研究，但我觉得还不够彻底明确，就是对某些人来说，它似乎会引发抑郁。
I mean, one that's sort of been studied some, but I think not in a way that's super, super conclusive, is for some people, it does seem to provoke a depression.
一直有人担心会出现自杀倾向增加的情况，但到目前为止的研究并未证实这一点，不过这仍然是人们关注的一个问题。
There's been this concern about increased suicidality that has not borne out in studies thus far, but, like, is on the radar as a thing that people are concerned about.
但这些精神神经方面的并发症，我非常关注并一直在留意。
But these psychiatric neurologic complications, I'm interested in and paying attention to.
这些药物最常见的副作用是胃肠道反应。
The most common side effects with these drugs are the GI side effects.
比如严重的恶心、呕吐和便秘。
So, like, bad nausea and vomiting and constipation.
因此，我非常关注如何更清晰地确定开具这些药物的标准治疗方案，以尽量减少这些副作用，以及未来如GLP-1 2.0、3.0、4.0这类药物是否会改善副作用谱，因为这将产生非常大的影响。
And so I'm really interested in both increased clarity around what standard of care looks like for prescribing them to minimize those side effects and whether these future, like, GLP-one two point o, three point o, four point o's are going to improve that side effect profile because that would actually make a very big difference.
对。
Right.
因为有些人无法耐受这些副作用。
Because there's people that can't tolerate their side effects.
是的。
Yeah.
我的意思是，有些人刚开始会严重恶心呕吐，因为他们还不知道该怎么在服药期间饮食，比如他们吃得还是太多。
I mean, some people are really nauseous and vomit at the beginning because they just haven't figured out how to eat on the drugs, like, they're still eating too much.
但有些人则有严重的便秘，根本无法忍受。
But some people have, like, constipation that they just can't tolerate.
有些人会持续感到恶心，而且情况不会好转。
Some people are persistently nauseous in a way that doesn't get better.
对大多数人来说，情况会好转。
For most people, it gets better.
但这确实是一个真正的限制因素。
But that's a real, like, rate limiting step.
因此，存在一个由我所属的领域和媒体构成的舆论世界，至少一年来都把这个故事搞砸了。
So there's a world of discourse and media, which I belong to, which bungled this story for at least a year.
在你所治疗的患者群体中，远离这些讨论的实际情况到底是什么？
In the world of the patient populations who you treat, like, what was actually happening far away from the discourse?
你能给我讲讲早期的故事吗？比如，在你的诊所里，哪些类型的患者在服用这些药物？它们对患者产生了什么影响？
Can you just tell me stories, like, from early on, like, what type of patient was taking these medicines at your clinic, and how is it affecting them?
当然可以。
Sure.
我在纽约市工作。
So I work in New York City.
纽约州的医疗补助政策非常优厚。
New York State has generous Medicaid.
纽约市的公立医院系统有自己的药房，他们做了一件我并不完全理解的了不起的事——即使在普通社区药房很难获得GLP-1药物的时期，他们依然成功地为患者提供了这些药物的获取渠道。
New York City's public hospital system has its own pharmacies, and they did some amazing job I don't totally understand, in which they were able to provide access to the GLP-1s even during the period when it was very, very hard to get them at sort of regular community pharmacies.
因此，得益于这种优厚的保险政策和我们医院药房的可及性，我有幸从2023年或2024年起，就能为那些贫困的糖尿病患者开具司美格鲁肽，而这些患者 otherwise 根本无法获得这种药。
And so between both that sort of generous insurance and that access in our hospital pharmacy, I have had this incredible good fortune of being able to prescribe Ozempic for diabetic patients since, like, 2023 or 2024 who are poor and otherwise would not have access to it.
对吧？
Right?
这是一个巨大的问题，因为对于大多数像我这样的患者来说，他们还没有用上这种药，因为他们的保险不覆盖。
And this is, like, a huge issue is that, like, for most patients like my patient population, they aren't on it yet because their insurance doesn't cover it.
是的。
Yeah.
或者即使保险覆盖了，也只限于非常狭窄的适应症，患者还是很难获得，或者遇到各种障碍。
Or if their insurance covers it, it covers it only for a very narrow set of indications, and they have trouble getting it or whatever it is.
我的患者从始至终都能获得这种药。
My patients have been able to get it the whole time.
我认为，对于像我这样面对高疾病负担的弱势群体来说，这在初级医疗领域简直是一次奇迹般的突破。
And I do think it's sort of like a miracle breakthrough in primary care for underserved populations that have the morbidity burden that my patients have.
我的大多数患者都有糖尿病、高血压、高胆固醇，以及某种程度的肾病，还可能伴有糖尿病的其他并发症，比如眼部视网膜病变和脂肪肝。
So most of my patients have diabetes and high blood pressure and high cholesterol and some degree of kidney disease and maybe some degree of other complications of diabetes, like retinal disease in their eyes and fatty liver disease.
在我的收容所诊所，我的大多数患者还有某种成瘾史，比如酒精或其他物质滥用。
Most of my patients also have some addiction history in my homeless clinic, so alcohol or other substances.
根据我的经验，对于那些我能够成功开具奥司他韦处方的患者——也就是我能获得报销的那些——它确实对所有这些问题都有显著帮助。
And it's been my experience that for the patients for whom I've been able to prescribe Ozempic, which is the one that I've been able to get paid for, it really does help with all of those things.
他们的糖尿病得到了改善。
Like, their diabetes improves.
他们减了体重。
They lose weight.
他们的慢性疼痛也缓解了。
Their chronic pain improves.
他们的血压得到了改善。
Their blood pressure improves.
他们的胆固醇指标也好转了。
Their cholesterol markers improve.
患者们真的很喜欢它。
And patients really like it.
我的意思是
I mean
他们怎么说的？
What did they say?
比如，我有个患有严重偏执型精神分裂症的女士，她一直在用这个药。
Like, I had I had this great paranoid schizophrenic lady who was on it.
她是我在初级护理中第一个开这个药的病人。
She was the first patient I ever prescribed it to in primary care.
她来我办公室时，平时就有点精神异常，但她按时吃药。
And she was in my office, and she's sort of, like, a little bit psychotic at baseline, but she takes her medicines.
她给我讲了个故事，我有点听不懂，说是有人在窃听她的电话。
So she's telling me some story, like, I kinda can't follow, but, like, some people who have been, like, tapping her phone.
然后我说：哇，真的吗？
And then I said, oh, wow.
我看着她的病历，发现她瘦了大约12磅左右。
You lost, like, 12 pounds or something because I'm looking at her chart.
她停顿了一下，突然专注起来，说：我自从1996年以来就没这么轻过。
And she paused and she, like, locks in, and she goes, haven't weighed this much since 1996.
我当时都惊呆了。
And and I died.
我当时就想，加油，姑娘。
Like, I was like, you go, girl.
太棒了。
Like, amazing.
真为你高兴。
So happy for you.
对于我很多病人来说，情况确实如此，他们在心理和身体上都感觉更好了。
And that's, like, that's been true for a bunch of my patients, that they feel better in their bodies both psychologically and physically.
但并不是对所有人都有效。
And they don't work for everybody.
当然，有大约百分之五到十的人因为副作用太强而无法耐受。
There are certainly, you know, five to ten percent of people who don't tolerate them because the side effects are too much.
有些人就是比普通人更容易恶心，然后他们就会说，我实在受不了了。
Like, some people just get much more nauseous than the average person, and then they're just like, I can't do this.
我不喜欢它。
I don't like it.
有几个人在我的个人生活中提到，而不是在我的诊疗中，说他们觉得自己的情绪低落，可能跟这些药物有关。
A few people have said more in my personal life than in my practice that they thought that they felt low on them, that that made them feel a little bit depressed.
嗯哼。
Mhmm.
在我的诊疗中还没遇到过这种情况。
I haven't had that happen in my practice.
但你知道，这说明了为什么有些人无法耐受这些药物，原因有很多。
But, you know, that's just to say that there are bunch of reasons why some people don't tolerate them.
但对于那些能耐受并且有效的患者来说，这是一种非常了不起的干预方式。
But for people who tolerate them and for whom they work, they're an incredible intervention.
我的大多数患者每天要服用八到十种药物。
Most of my patients are on, like, eight to ten medicines a day.
而对他们来说，每周打一针就能减重、改善糖尿病、降低高血压、改善高胆固醇，减轻体重的同时还能减少体内炎症，从而缓解疼痛、改善抑郁情绪。
And for them to be able to take one shot a week, lose weight, improve their diabetes, improve their high blood pressure, improve their high cholesterol, you know, carrying less weight and also have less inflammation in their body, so their pain is better, their depression is better.
这真的是一种非常了不起的治疗选择。
Like, that's an extraordinary thing to be able to offer them.
这不是每个人的体验，但对于那些有效的人而言，它的效果比我曾经给过患者的任何其他单一干预措施都要好，除了那些能根治的疗法。
It's not everybody's experience, but for people for whom it works, like, it it works better than any other single intervention I've ever given someone other than curative ones.
因此，我对此无比感激，也对此感到极度兴奋。
And so, like, I'm unbelievably grateful for them, and I'm incredibly excited about them.
你知道的。
You know?
随着这场开发更优、更有效、更精准的GLP-1药物的竞赛持续进行。
Like, I think as there's this arms race in developing better, more effective, more targeted GLP-1s.
随着我们对如何根据不同病症正确使用这些药物的研究越来越多，等等，等等，我的意思是，它已经产生了影响，但必将彻底改变初级医疗实践。
And as we get more and more studies about how to dose them correctly for different conditions, etcetera, etcetera, like, you know, I mean, it already has, but it will absolutely revolutionize primary care practice.
医生。
Doctor.
贝达德表示，这场变革的部分原因在于，或许令人惊讶，或许也不意外——2023年和2024年这些药物需求激增的一个副作用是价格被拉低了。
Bedard says that part of this revolution has come because, maybe surprisingly, maybe not, one side effect of the huge demand surge for these drugs in 2023 and 2024 is that the price has been driven down.
当像司美格鲁肽这样的药物制造商无法满足需求时，配药药房便进入市场，以低得多的价格销售配制版本。
When the manufacturers of drugs like Ozempic couldn't meet demand, compounding pharmacies entered the marketplace, selling compounded versions at a much lower price.
这进一步压低了品牌GLP-1药物的价格。
That ended up pushing prices further down, even on the name brand GLP-1s.
因此，司美格鲁肽——不久前无保险时每月售价1200美元——现在网上最低只需150美元每月。
So now semaglutide, which not so long ago cost $1,200 a month without insurance, can be found online for as low as $150 a month.
一个终于似乎有点儿奏效的医疗市场。
A health care market that, for once, seems to have kind of sort of worked eventually.
我们再休息一次，回来后，医生。
We're gonna take one more break, and when we come back, Doctor.
贝达德分享了她对那些非适应症使用这些药物的人的看法。
Bedard gives us her take on people who are taking these drugs for decidedly off label use.
欢迎回到节目。
Welcome back to the show.
在你的社交生活中，有没有非患者的人，比如家人，还在问这些药的事？
Do you just in your social life, do you have, like, non patient people, like, family members still asking about the drugs?
哦，一直都在问。
Oh, constantly.
一直如此。
Constantly.
确实一直如此。
So Constantly.
比如，我每天都会接到非正式的司美格鲁肽咨询。
Like, I take, like, an unofficial Ozempic consult a day.
你
What do
你现在会怎么告诉别人呢？
you tell people right now?
我的意思是，我非常支持GLP-1类药物。
I'm I mean, I am very GLP-1s supportive.
所以，这得具体情况具体分析。
So, you know, it's case to case.
并不是每个人都适合。
Like, it's not for everybody.
但我可以给你一些例子，比如这类情况。
But I will give you sort of examples of, like, the kinds of things.
比如，我生活中有很多女性正在经历产后体重增加或孕期体重增加，产后仍觉得自己超重；有些人一想到再次怀孕就非常焦虑，因为她们之前体重增加太多，感觉再也回不到原来的自己，也不想再增重了。
Like, you know, I have lots of women in my life who are struggling with postpartum weight gain or, like, pregnancy weight gain and not being postpartum feeling overweight or people who one of their real anxieties about getting pregnant again is that they gained a huge amount of weight, and they don't feel like they're back in their own bodies, and they don't wanna gain more.
我非常支持人们在一段时间内使用GLP-1药物，帮助他们减掉那些突然增加且难以减掉的体重。
I'm really supportive of people using a GLP-one for a period of time to help them lose, you know, weight that they gained really suddenly and are having a hard time losing.
当然，有些人一生中长期有饮食失调的历史。
There are obviously some people who have long histories of eating disorders in their lives.
对吧？
Right?
在这种情况下，我认为如果你这么做，实际上并不会好。
And where you think, I think if you do this, this is not gonna be great for you, actually.
我觉得这会重新点燃一系列你已经花了大量精力去克服的强迫性思维。
Like, I think that this is reigniting a series of obsessions that, like, you've done a lot of work to try to get past.
对于这些人，我认为他们不应该考虑使用GLP-1药物。
For those folks, I don't think that they should, you know, entertain the idea of a GLP-one.
但对于很多人来说，我认为这样做是可以的。
But for lots of people, I think it's a fine thing to do.
你有没有和那些谈论用它来管理成瘾的人交流过？
Do you talk to people who are talking about using it, I guess, off label to manage addictions?
我认识一个人，他服用它是为了减少在推特上发帖。
I have so I don't want I I know one guy who was taking it so that he would post on Twitter less.
真的吗？
Really?
是的。
Yeah.
有效果吗？
Did it work?
他说有效。
He said so.
但他最近又开始频繁发帖了，所以也许吧，我不确定。
And then he's posting a lot recently, so maybe he's I don't know.
你知道吧？
You know?
因为我真的以为它是治疗推特使用成瘾的良药。
Because I really thought it was a cure for Twitter use.
那些人我不会。
Those people I would no.
我会拿着一把吹枪站在别人家门外，就像
I would stand outside other people's houses with, like, a blow I gun and just like
我的意思是，我觉得是的。
mean, you know, I think yes.
我确实认识一些人，我有一个亲密的朋友，他尝试的主要动机是想少喝酒。
I'd absolutely have people who I I have a close friend who's primary motivation in trying it was that he wanted to drink less.
他可能也想减掉十到十五磅，但光为这个目的他大概不会去吃。
He also probably wanted to lose 10 or 15 pounds, but, like, probably wouldn't have taken it just for that alone.
是的。
Yeah.
问了。
Asked.
我说，好的。
And I said, yeah.
试试看。
Try it.
看看你能不能耐受。
See how you tolerate.
你知道，另一点是，它们相当安全。
You know, the other thing is that they just are quite safe.
这并不意味着每个人连续六十年每周服用都是安全的。
That doesn't mean that they're safe for everybody to take for sixty years week after week.
你知道吗？
You know?
我们并没有完全掌握确切的数据，但我们已经有了这种药物二十年的数据，我们相当清楚，只有一小部分人群绝对不适合使用。
Like, we don't totally have exactly that data, but we have twenty years of data about this class of medicines, and we have a pretty good sense of there is a very narrow slice of the population who they're totally inappropriate for.
对于大多数有某些罕见癌症家族史的人来说，给予他们注射并观察耐受情况是完全合适且合理的。
If you've had a family history of certain rare cancers for the majority of people, giving them a shot and seeing how you tolerate is totally appropriate and fine.
所以这位朋友确实尝试了。
And so this friend, like, took at them.
他并不认为自己是酒鬼，但他认同自己是一个希望减少饮酒、且每天饮酒的人。
He didn't identify as an alcoholic, but he identified someone who wanted to drink less and who drank daily.
对于这位朋友来说，他服用了六个月左右，或者四个月，彻底改变了他与饮酒的关系。
And for this friend, he took them for six months or something or four months, totally changed his relationship to drinking.
我想他已经停药一段时间了，他说自己没有再像以前那样饮酒。
I think he's been off now for a little while, and he said he's not back to drinking the way that he was.
即使他现在不像服药期间那样强烈抑制饮酒欲望，他仍觉得这种关系对他而言已经发生了改变。
He feels that relationship feels altered for him even if he's not as suppressed in his desire as he maybe was when he was, like, on the medicine week after week.
我还有一个最后的问题要问贝达德医生。
I had one last question for doctor Bedard.
我想知道她对一类药物有什么看法，这类药物与GLP-1类似，但在我的观点中与之有相当大的不同，即人们现在使用的各种野生型多肽分子——我们在节目其他地方已经讨论过这些药物。
I wanted to know if she had a perspective on a class of drugs that are adjacent to, but in my view, fairly different from GLP-1s, Internet peptides, the wilder west of molecules many people are now using, drugs we've covered elsewhere on the show.
我认为GLP-1和肽类在某种程度上都代表了健康、保健和医学领域的一场更大转变，即从将药物视为治疗疾病的工具，转向将制药产品视为帮助人们获得理想感受的手段。
I think that I think that it is both GLP-1s and peptides to some degree are part of a larger shift in health, wellness, medicine, which is this, like, paradigm shift between thinking of medicines as things that we use to treat illness to thinking of pharmaceutical products as something that we offer people to help them feel the way they want to feel.
这是否是一种
And is that a
糟糕的转变吗？
bad shift?
这是一种中性的转变吗？
Is that a neutral shift?
我认为这是一种复杂的转变。
It's a complicated shift, I think.
所以，对我来说，比肽类更合适的例子是激素替代疗法被用于成千上万种不同的适应症。
So, you know, the the better example that to me than peptides is, like, the use of hormone supplementation for a million different indications.
对吧？
Right?
这又是另一个庞大的讨论话题。
Like, that's another huge discourse.
就像是，女性在四十岁出头时，当她们感觉到自己诊断为围绝经期症状时，就开始服用雌激素补充剂。
It's like, you know, women taking estrogen supplementation in their early forties when they start to feel what they self diagnose as perimenopausal symptoms.
女性服用睾酮，已经有不少文章讨论过这个话题。
Women on testosterone, there's been a bunch of essays about that.
男性服用睾酮，你知道，这是一种完全不同的健康护理理念，这并不是我投身医疗行业的初衷，也与我接受培训时的模式不同。
Men on test you know, like, it's a very different way of conceptualizing the role of health care than it's not why I went into health care, and it's also different from the sort of paradigm I trained in.
但我也在努力保持中立，思考患者与医疗提供者之间关系的变化——转向一种更注重共同设定目标、共同决策的模式，但这并没有完全回答你关于肽类的问题。
But I'm also a little bit trying to remain neutral about this in thinking about the changing relationship between patients and providers to one that's a more sort of shared goal setting, shared decision making model, which doesn't quite answer your peptides question.
但我基本上把肽类、GLP-1类药物、整容手术等都看作是一体的。
But I I kind of see all of, like, the peptides, the GLP-1s, the cosmetic procedure stuff.
这都源于一种共同的感受：我的身体状态不是我想要的感觉。
It's like all part of a thing of, like, I I don't feel the way I want to feel in my body.
我的外貌也不是我想要的样子，诸如此类。
I don't look the way that I wanna look in body, etcetera, etcetera.
我会寻求医疗干预，帮助自己成为我想成为的样子。
I'm I'm going to seek medical intervention to help me become the thing that I wanna become.
我对这件事有非常复杂的反应，但我目前还没有明确的看法。
I I have really complicated reactions to it, but I'm I don't yet have a definitive opinion about it.
我正在努力认真思考这个问题。
I'm really trying to think it through.
我不确定你所描述的是：我们以前认为只是美容的干预措施，现在变得越来越被社会接受；还是说情况更复杂——即，我们过去认为是美容的干预，现在在心理上已经将其归类为医疗行为。
I can't tell if what you're describing is that interventions that we just would have understood as cosmetic before are becoming much more socially acceptable, or if it's more complicated, which is that, like, interventions, like, we thought of as cosmetic, we're now in our own minds labeling as medical.
我认为是第二种情况。
I think it's the second one.
我觉得，以一种奇怪的方式，我们把人类生命周期中的许多体验医学化了。
So I think that we have, in a weird way, medicalized a lot of the experience of being, like, in the human life cycle.
你知道的吧？
You know?
是的。
Yeah.
这很复杂。
And that's complicated.
你知道吧？
You know?
而且，这些都是一些问题和讨论话题之类的。
And again, like, these are all sort of questions and discourse topics, etcetera, etcetera.
它们离我的医疗实践、我的病人的生活和病人的身体太远了。
They're so far afield from my medical practice and my patients' lives and my patients' bodies.
它们也离真正困扰病人、真正夺走人们生命的事情太远了，等等。
And they're so far afield from sort of what are the things that sick people actually live with, what are the things that actually kill people, etcetera, etcetera.
因此，在明确指出我对GLP-1讨论的所有最初担忧同样适用于这种更广泛的、围绕以自我实现为目的但正被医学化的其他干预措施的讨论之前。
So with the sort of large caveat that all of my initial anxieties about the GLP-one discourse apply to this other sort of wider discourse around other interventions that are for self fulfillment but are sort of being medicalized.
我正努力在对这些话题做出本能的道德恐慌反应之前，先稍微理性地思考一下。
I'm trying to be, like, a little bit thoughtful before I just sort of react to them as a knee jerk moral panic around those.
但你感觉不安，却又不确定这种不安从何而来。
But it's like you feel uneasy, but you feel uncertain about your uneasiness.
是的。
Yeah.
我正在认真地思考这个问题。
I'm, like, really working through it.
我认为这是一种思想上诚实的立场。
I think that's a intellectually honest position.
谢谢。
Thank you.
谢谢你谈论这个话题。
Thank you for talking about this.
不客气。
My pleasure.
谢谢你邀请我。
Thank you for having me.
医生。
Doctor.
拉切尔·贝达德是一位医生兼作家，她的文章讲述了奥兹empic的兴起，我们会在节目说明中提供链接。
Rachael Bedard, she's a doctor and writer, will have a link to her story about the rise of Ozempic in the show notes.
另外，必须说，这场对话还有一个部分，是我本周后和朋友们聊得最多的，但它属于一个稍显相关的话题。
Also, have to say, there was one more part of this conversation, which it was a part I found myself talking the most about with friends this week afterwards, but it was on a slightly adjacent topic.
所以我们更深入地探讨了‘美容医学’这个概念，即美容干预与医疗干预的交汇点，以及中年人如何考虑使用睾酮或雌激素，或去皮肤科做激光治疗，试图让自己看起来更像安妮·海瑟薇，或者男性前往土耳其做新的发际线手术。
So we got more into this idea of cosmedicine, like the place where cosmetic interventions and medical interventions kind of meld together, and about how there are middle aged people who are thinking about interventions like taking testosterone or estrogen or going to the dermatologist for lasers to try to look more the way they think Anne Hathaway looks or men going to Turkey to get a new hairline.
我不知道我们该如何看待这个时代——变老似乎正变得越来越可选，而互联网上许多人似乎永远都是35岁。
I don't know how we're supposed to think about this era where looking older seems to be becoming more optional, where many people on the Internet seem forever 35.
和贝达德医生交谈，也帮助我理清了这些想法。
And talking to doctor Bedard, is also working this stuff out, it really helped me.
这些想法早已在我脑海中盘旋。
These ideas have already been swirling around my brain.
它们因此稍稍安定了一些。
It settled them a little bit.
如果你想听这段对话，我们将会以一个小附加功能的形式发布在‘隐身模式’中。
If you wanna hear that conversation, we're gonna publish it as an extra small feature on incognito mode.
你可以在 searchengine.show 上注册订阅。
You can sign up for that at searchengine.show.
如果你已经注册了，现在就在你的信息流里。
If you're already signed up, it is in your feed now.
《搜索引擎》由Audacy出品。
Search Engine is a presentation of Audacy.
本节目由我PJ·沃格特和特鲁希·皮特马内尼创作。
It was created by me, PJ Vogt, and Truthi Pitmaneni.
加勒特·格雷厄姆是我们的高级制作人。
Garrett Graham is our senior producer.
艾米莉·莫拉雷是我们的助理制作人。
Emily Moltare is our associate producer.
主题曲、原创音乐及混音由阿尔明·巴扎里安制作。
Theme, original composition and mixing by Armin Bazarian.
我们的制作实习生是派珀·杜蒙。
Our production intern is Piper Dumont.
派珀还为本期节目进行了事实核查。
Piper also fact checked this episode.
我们的执行制片人是莉亚·里斯·丹尼斯。
Our executive producer is Leah Reese Dennis.
感谢Audacy团队的其他成员，包括罗布·莫兰迪、克雷格·考克斯、埃里克·多内利、科林·盖恩纳、摩尔、库兰、约瑟菲娜·弗朗西斯、柯克·考特尼和希拉里·舒夫。
Thanks to the rest of the team at Audacy, Rob Morandi, Craig Cox, Eric Donnelly, Colin Gaynor, Moore, Curran, Josephina Francis, Kirk Courtney, and Hillary Schuff.
此外，如果您有业务希望在我们的节目中做广告，请给我们发邮件。
Also, if you have a business which you would like to advertise on our show, please email us.
邮箱地址是 pjvote85@gmail.com。
Email address is pjvote85@gmail.com.
邮件主题请写：广告。
Subject line, advertising.
如果您想支持我们的节目，获取无广告剧集、零重复内容和独家音频（包括本周的），请考虑在 searchengine.share 注册使用隐身模式。
If you'd like to support our show, get ad free episodes, zero reruns, and bonus audio, including this week, please consider signing up for incognito mode at searchengine.share.
感谢收听。
Thanks for listening.
我们下周见。
We'll see you next week.
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