#320 – AMA 64: New insights on GLP-1 agonists (Ozempic, Wegovy, Mounjaro) - efficacy, benefits, risks, and considerations in the rapidly evolving weight-loss drug landscape

大家好。

Hey, everyone.

欢迎收听《The Drive》播客的问答节目预告。

Welcome to a sneak peek ask me anything or AMA episode of the drive podcast.

我是主持人阿提亚。

I'm your host, Attia.

在这期短节目的最后，我会告诉大家如何完整收听问答节目，以及我们为会员准备的其他福利。

At the end of this short episode, I'll explain how you can access the AMA episodes in full along with a ton of other membership benefits we've created.

或者你现在就可以访问 peterattiamd.com/subscribe 了解更多。

Or you can learn more now by going to peterattiamd.com forward slash subscribe.

话不多说，下面就是今天问答节目的精彩预告。

So without further delay, here's today's sneak peek of the Ask Me Anything episode.

欢迎收听第64期问答节目。

Welcome to Ask Me Anything AMA episode 64.

今天和我一起主持的还有我的搭档尼克·斯坦森。

I'm once again joined by my cohost, Nick Stenson.

今天这期节目，我们要聊一个以前聊过的话题，但自从上次聊完之后，这个话题一直备受关注，那就是GLP-1受体激动剂。

In today's episode, we cover a topic that we've addressed in the past but has continued to gain significant attention since we last spoke and that of course is the topic of GLP-one agonists.

你可能听说过这些药，像奥泽匹克和蒙加罗，但我们今天会聊得更深入。

You may have heard of these drugs Ozempic and Mounjaro but we go much deeper into this.

这些药现在这么火，而且我们对它们的了解，自从上次聊过之后，可以说有了突飞猛进的进展，所以我们就觉得，应该好好回答一下大家关于这些药的问题，也分享一下我们在病人身上积累的经验。

Now, how these drugs have gained popularity and given how our knowledge on them has advanced probably non linearly since we last discussed them, we felt it was appropriate to address many of your questions on these topics and what we've learned through our own experience with patients.

在这期对话里，我们首先会简单介绍一下GLP-1分子是什么，这些药是怎么起作用的，以及为什么现在它们这么有用。

In this conversation, we begin with a very quick background on what a GLP-one molecule is, how these drugs work and why they are finding so much utility today.

我们会重点聊聊现在对它们长期效果的了解，这个效果比我们以前知道的要更持久。

We focus on what we now know about their long term efficacy, which is longer than what we knew in the past.

还有我们知道的副作用，以及停药之后会发生什么。

What we know about side effects and what we know about what happens when you stop taking these drugs.

我们还会专门聊聊它们对身体成分的影响。

We also talk specifically about their effects on body composition.

这个以前我们没法从临床试验文献里得出结论，但现在我们确实有了这些数据。

This is something we couldn't speak to from clinical trial literature before but we now in fact have that data.

我们讨论了抗阻训练在这些药物中的作用，以及不同GLP-1受体激动剂之间的差异。

We talk about the role resistance training plays on these and we talk about the differences between the specific GLP-one receptor agonists.

比如，目前市面上这两种药，是不是有一种比另一种更好？

For example, is one of the two on the market today better than others?

我们还谈到了复方药房在其中扮演的角色。

Talk about the role compounding pharmacies are playing in this.

我们讨论了口服药和注射剂的区别。

We talk about orals versus injectables.

还有哪些其他健康状况可能适合用这些药物治疗。

What some other health conditions might be that are amenable to treatment with these drugs.

我们还谈到了市面上现有的GLP-1激动剂或其他受体激动剂，哪些看起来有前景，至少有一种可能更有前景。

And we talk about the types of GLP-one agonists or other receptor agonists that are on the market and that appear to be promising and at least in one case potentially more promising.

如果你是订阅用户，想观看本期播客的完整视频，可以在节目笔记页面上找到。

If you're a subscriber and want to watch the full video of this podcast, you can find it on the show notes page.

如果你不是订阅用户，可以在我们的YouTube页面上观看视频的预览片段。

And if you're not a subscriber, you can watch the sneak peek of the video on our YouTube page.

那就不多说了，希望你喜欢第64期AMA。

So without further delay, I hope you enjoy AMA number 64.

彼得，

Peter,

欢迎来到新一期AMA。

welcome to another AMA.

你最近怎么样？

How are you doing?

我挺好的。

Doing very well.

谢谢你的邀请。

Thank you for having me.

我看你今天换了个新地方。

I see you're in a new location today.

你想不想跟大家说说

Do you wanna let people

知道为什么吗？

know why?

嗯，经过一番规划，我们决定扩展整体风格，并为此专门打造一个工作室。

Well, after some planning, we've decided to expand the look and feel and create a dedicated studio for this.

今天能迎来我们的首次棚内播客，真的很兴奋。

So excited to have our inaugural in studio podcast today.

对于不了解的人来说，我们以前每次录制时，都要把你的办公室，也就是你真正的工作办公室，临时改造成一个录音棚。

For people who don't know, we used to transform your office, your actual work office into a studio every time we were recorded.

所以现在不用每周都这么折腾了，感觉是不是好多了？

So how much nicer is it to not have that done each week?

那感觉就像你终于不用每周都去做根管治疗一样舒坦。

It's as much nicer as it is when you have to stop having a weekly root canal.

那那挺好的。

That's that's good.

挺好的。

That's good.

背景噪音也少了很多，不管是小孩还是狗叫之类的。没错。

Much less noise going on from background from kids or dogs or anything of that nature as well That's right.

在新录音室里，这总是好的。

In the new studio, which is always good.

今天的AMA挺有意思的，其实算是我们内部的小秘密吧。我们做播客通常从录制到发布有十到十二周的延迟，这是我们的工作方式。

For today's AMA, it's actually funny because it's kind of a little inside baseball, how we do the podcast is usually there's anywhere from a ten to twelve week delay from podcast recording to release just with how we work.

但这一期会先发布，然后我们再回到旧录音室，按照原来的发布计划，但录制计划不变。

But this one is gonna be released first, and then we're gonna go back to the old studio a little bit and the release schedule, but not the recording schedule.

原因是我们今天要聊的话题想尽快发布，因为它似乎是我们聊过的所有话题中变化最快的，就是GLP-1类药物，比如奥泽匹克、替尔泊肽，大家可能都听说过。

And the reason why is we're covering a topic today that we want to turn around and get out as quickly as possible because it seems it's a topic that changes more than almost anything else that we talk about, which is GLP-1s or Ozempic, tirzepatide, you kind of name it, as people have heard of them.

我回想了一下，你和鲍勃第一次聊这个话题是在2021年11月，那是我们发布那期节目的时间。

And I actually look back because you and Bob first talked about this November 2021 is when we released that episode.

我们在2023年3月做了后续跟进。

We did a follow-up March 2023.

我觉得在那段时间里，没有哪个话题的兴趣变化比这个更大。

And I don't think there's been a topic that has had more change in terms of interest in that period of time than this.

而且我在上次播客里也说过，我记得你和鲍勃第一次聊到想做一期关于GLP的问答时，我当时就想，我们为什么要做这个。

And I still I said at the last podcast we did this one too is I remember the first time you and Bob talked about wanting to do a GLP AMA and I was like, have no idea why we're doing this.

那是最技术性的内容。

It was the most technical thing.

完全没道理。

It made no sense.

没人讨论这个。

No one was talking about it.

现在感觉到处都是。

And now it seems like it's everywhere.

即使从我们上次做这个节目到现在这十八个月里，变化也很大。

Even since the last eighteen months when we did the last one, so much has changed.

所以这次我们会把所有相关的内容都覆盖到。

And so in this one, we're gonna cover everything as it relates to these.

我们会一点一点地过一遍，简单回顾一下它们是怎么起作用的，但如果大家想深入了解细节，之前的问答节目是最好的参考。

And we'll just go through piece by piece and we'll do a little recap of how they work, but previous AMAs will be best if people wanna go into detail there.

我们不会花那么多时间。

We're not gonna spend as much time.

我们会花更多时间讨论我们现在知道的这些信息，以及它们如何运作，药物和复方注射剂之间的区别，我们对体重反弹的了解，还有安全性方面的数据。

We're gonna spend much more time on what we know about this now and how this works, the difference between the drugs compounded injection, what we know about weight regain, safety profiles.

你之前几次聊这个话题的时候，信息量远没有现在这么多。

The past few times you talked about this, there just wasn't as much information as there is now.

所以我觉得这会很有意思，因为我觉得这也是一个你可能会根据我们之前的对话稍微改变看法的话题。

So I think it'll be really interesting because I think it's also one where you maybe have changed your mind a little bit based on past conversations that we had.

所以这会是一期很好的节目。

So it will be a really good one.

我觉得会非常有趣。

I think it will be really interesting.

那么，在我们开始之前，你想补充点什么吗？

And with all that said, do you wanna add anything before we start rolling into it?

是的。

Yeah.

其实，背景信息还挺多的。

Actually, quite a bit of context.

所以，你刚才说的那些，我再补充一点。

So everything you said, just to add on to that.

如果说有什么让我觉得特别有意思的，那就是我在刷Instagram的时候，看到三四年前自己谈论司美格鲁肽的视频，说实话，我甚至不一定同意当时自己说的那些话。

If there's one thing that I get a kick out of, it's I'm scrolling on Instagram and I see a video of me talking about semaglutide from three or four years ago and I frankly don't even necessarily agree with what I was saying at the time.

这就是事物发展的本质。

And that's just the nature of how things work.

我们的认知变化很大。

Our knowledge changes a lot.

所以，这也是我今天想再次讨论这个话题的部分原因。

And so that's part of my motivation for wanting to talk about this yet again today.

因为我们现在比三年前知道的要多得多，但我也想承认，还有很多我们不知道的事情。

It's that we know considerably more today than we did three years ago, but I also want to acknowledge all the things we don't know.

所以，这就是我想说的一点。

So, that's one point I'd want to make.

我想说的第二点是，至少这些药物的早期版本已经存在相当长一段时间了。

Second point I want to make is there's at least earlier generations of these drugs have been around for quite some time.

我第一次开这类药的时候，用的是利拉鲁肽，那差不多正好是十年前。

So, the very first time I ever prescribed a class of this drug was a drug called liraglutide and it's almost exactly ten years ago.

那是在2014年秋天，我给一位患者开了这个药。

It was in the fall of twenty fourteen that I prescribed that to a patient.

那个药效果其实不怎么样。

Not a particularly effective drug.

所以又过了六年，直到2020年秋天，我才给患者开了司美格鲁肽。

So, it would be another six years before I would prescribe semaglutide to a patient in the fall of twenty twenty.

那次体验完全不一样。

And that was a totally different experience.

那当然是在Ozempic获批用于治疗肥胖之前。

That was of course Ozempic before it had been approved for obesity.

所以，是的，我觉得我有很多话想说。

So, yeah, I think I just have a lot of stuff I want to talk about.

但你说得对，之前讲过的内容就没必要再重复了。

But to your point, there's no need to rehash stuff we've gone through before.

我记得在AMA第二十九期，我和Bob深入探讨了这些药物的生理机制，我们可能花了比必要更多的时间来解释胃肠道如何运作以及胃肠激素如何起作用。

I think it was AMA twenty nine where Bob and I did a very deep dive into the physiology of how these things work and we really probably spent maybe more time than we needed to explaining to people how the GI tract works and how GI hormones work.

所以，这里就不重复了。

So, not gonna do that here.

我们直接切入正题。

Let's cut right to it.

这类药物最初是为了治疗2型糖尿病而开发的。

So, are a class of drugs that were initially developed for the management of type two diabetes.

这主要是因为这类药物模拟一种叫做GLP-1（胰高血糖素样肽-1）的激素，它能刺激胰腺释放胰岛素。

And that was largely on the basis of the fact that these are a class of drugs that mimic a hormone called GLP-one, glucagon like peptide-one, that stimulates the release of insulin from the pancreas.

当然，如果你得的是2型糖尿病而不是1型，这是应对疾病的一种途径。

Which of course, if you have type two diabetes as opposed to type one diabetes, is one of the routes of trying to get around the disease.

当患者的胰腺不再分泌足够的胰岛素时，这会是你要尝试的一个方向。

When a patient's pancreas is no longer secreting sufficient insulin, that would be one half of what you would try to do.

当然，还有其他方面需要处理。

Of course, there's other things you try to do as well.

还要提高胰岛素敏感性，这样就不需要那么多胰岛素就能把葡萄糖送进肝脏和肌肉。

Want to increase insulin sensitivity and of course that makes it so that you don't actually need as much insulin to get the glucose into the liver and to the muscles.

所以，如果故事到这里就结束了，我们可能就不会讨论这个话题了。

So, if the story ended there, we probably wouldn't be talking about this.

如果这些药只是对2型糖尿病有帮助，而美国大约十分之一的人患有此病，那可能就不会引起太多讨论了。

If the story ended with these are great drugs to help people with type two diabetes, which roughly speaking about one in ten Americans have today might not be talking much about it.

如果只是降低糖化血红蛋白之类的，那当然很重要。

If it was lowering hemoglobin A1C and things like that, I mean that would be very important.

但为什么这成了热门话题呢？

But again, why is this such a topic?

因为司美格鲁肽带来了一些利拉鲁肽没有的效果，不仅患者的糖化血红蛋白改善了，体重也大幅下降。

The topic is because with semaglutide, something happened that didn't happen before with liraglutide, which was not only did patients have an improvement in their hemoglobin A1c, but their weight dropped dramatically.

这就引出了一个显而易见的问题：我们是否应该考虑用这些药物来帮助那些没有2型糖尿病的人减肥呢？

And so that led to the obvious question which is, should we be considering these drugs for weight loss in people who do not have type two diabetes?

当然，这就是三年前一系列试验提出的问题，而答案显然是肯定的。

And of course that was the question that was basically posed through a series of trials three years ago and the answer turned out to be emphatically yes.

我觉得我们不需要深入细节，但你能用一两句话简单提醒大家这些药到底是怎么起作用的吗？

I don't think we need to get into the details but what's the one zero one four sentence version for people as a reminder on how these drugs actually work?

我们先从最重要的器官——胰腺说起。

Let's start with the most important which is the pancreas.

就像我刚才提到的，它会刺激胰岛素分泌，同时减少胰高血糖素的分泌。

So as I mentioned a second ago, it's going to stimulate the release of insulin secretion and reduce glucagon secretion.

所以，这两方面共同作用，最终会降低血糖。

So, both of those are going to have a net effect of lowering blood sugar.

在空肠和回肠，也就是小肠的一部分，它会减缓胃排空和胃肠蠕动。

And the jejunum and the ileum, which are just parts of the small bowel, it's going to reduce gastric emptying and GI motility.

这样就会减慢肠道对葡萄糖的吸收，让胃保持饱腹感更久，顺便说一句，这可能部分与饱腹感的益处有关。

So, it slows absorption of glucose from the intestines and keeps the stomach full for longer, which by the way might partially relate to some of the satiety benefits.

在肝脏，它会减少肝脏产生葡萄糖。

In the liver, it reduces hepatic glucose production.

所以，当然，这大概就是二甲双胍在那边起的作用。

So, of course, again, probably something like what metformin is doing there.

最有趣的是，可能，我们后面会详细讲，在大脑里，它可能刺激饱腹感相关的神经回路，同时降低那些驱动食欲的回路的活动。

Most interestingly, potentially, and we'll talk more about this, is in the brain, it's probably stimulating pro satiety circuits and then decreasing the activity of the circuits that drive appetite.

再说一次，几年前我们讨论这个的时候，真的完全不知道它在减重中起了多大作用。

And again, I would say that a few years ago when we talked about this, we really had no idea how much that was driving weight loss.

我觉得现在我们有感觉它起了相当大的作用。

I would say today we have a feeling that it's doing quite a bit.

在脂肪组织本身，它增加从血液循环中摄取葡萄糖，并增加脂肪分解。

Within fat tissue itself, it's increasing glucose uptake from circulation and increasing lipolysis.

这有点反直觉，因为一方面它把葡萄糖从血液循环中拿走。

That's a bit counterintuitive because on the one hand that's taking glucose out of circulation.

这说得通，因为胰岛素敏感性提高了，但另一方面又反直觉，因为那应该让脂肪细胞变大。

That kind of makes sense due to increased insulin sensitivity, but it's also counterintuitive because that should make a fat cell fatter.

但当然，通过促进脂肪分解，它实际上增加了后端的通量。

But of course by driving lipolysis, it's actually increasing the throughput on the back end.

在肌肉里，它会增加葡萄糖的氧化。

In the muscle, it's increasing glucose oxidation.

也就是说，肌肉氧化葡萄糖的能力会增强。

So, the capacity of the muscles to oxidize glucose.

我们会在节目笔记里放一张非常清晰的图，详细展示这个过程，方便大家了解具体发生了什么。

We'll include a really nice figure in the show notes that goes through this in more detail so folks can see what's happening.

它还有很多其他作用，不过我觉得现在就不多说了。

There are lots of other things it's doing that I don't think I'll talk about now.

我会等到讨论具体器官相关的问题时再讲。

I'm gonna wait and talk about them when we get to organ specific questions.

比如，它对心脏具体有什么影响？

For example, what is it doing specifically in the heart?

对肾脏又有什么作用？

What is it doing in the kidney?

这些都是目前非常受关注的话题。

These are topics of huge interest today.

就像我们刚才提到的，距离我们上次聊这个话题已经差不多十八个月、十九个月了。

As we kind of mentioned, it's been about almost eighteen months, nineteen months since the last time we spoke about this topic.

那时候，还有很多未知数。

And so back then, there was a lot of unknowns.

所以我们当时能聊一些东西，但也有很多不确定的地方，因为这些药太新了。

So we were able to speak about certain things, but then there was also just unknowns with how new these drugs were.

那我们现在学到了什么呢？

And so what have we learned?

跟我们上次深入聊这个话题时相比，现在有什么快速概览吗？

What's like a quick overview of what we know now compared to what we knew last time we did a deep dive on this?

对。

Yeah.

有很多。

There's a lot.

我的意思是，我先说一点，上次我们聊的时候，其实只谈到了两种药。

I mean, I'll start with just the fact that when we last spoke about this, we were talking really just about two drugs.

我们当时在讨论一种叫司美格鲁肽的药，它的品牌名是……

We were talking about a drug called semaglutide, which again, the brand name for that.

大家最早提到的那个品牌叫奥泽匹克。

The first one that people talked about was Ozempic.

后来为了用于肥胖适应症，而不是仅仅用于二型糖尿病，它被重新命名为维格维。

It was just rebranded as Wegovy for the obesity indication as opposed to just type two diabetes.

然后我们还讨论了另一种叫替尔泊肽的药，这是一种稍微不同的药，我们一会儿会看到，它效果稍微好一些，而且它不仅作用于GLP-1，还作用于另一种激素GIP。

And then we spoke about another one called tirzepatide, which is a slightly different drug, as we're gonna see in a moment, a slightly better drug and a drug that works not just on GLP-one but also on GIP, another hormone.

它的品牌名叫蒙加罗，但那是用于糖尿病的版本。

It goes by the brand name Mounjaro, but that's the diabetes version.

所以蒙加罗之于奥泽匹克，就像它的肥胖适应症版本泽普邦之于维格维一样。

So Mounjaro is to Ozempic what its obesity counterpart, which is called Zepbound is to Wegovy.

说实话，这些名字我根本记不住。

Honestly, I can't keep track of all these names.

所以我尽量只记它们的通用名，也就是司美格鲁肽和替尔泊肽。

So I just sort of try to remember the actual generic name of it, which is of course semaglutide and tirzepatide.

今天我们还要聊一种还没获批的药，但我觉得大家对这个特别感兴趣。

Today we have another one that we will talk about that is not yet approved, but it's the one I think people are very interested in.

那么，总体来看，我们今天要讲什么？

So, big picture, what do we have today?

为什么今天又要聊这个？

Why would we talk about this again today?

因为我们现在有了更多的安全数据。

Well, we have much more safety data.

而且我觉得，对于任何新药，尤其是这种在市场上渗透率这么高的药，我们得特别小心，要搞清楚上市后监测的情况。

And obviously one of the things that I think we should be very cautious about with any new drug, especially a drug that has this much penetration in the market is we want to understand what's happening in post approval surveillance.

所以，一种药即使在三期临床研究中获批了，也不意味着FDA就不再关注了。

So, just because a drug gets approved during what's called a phase three study doesn't mean the FDA stops paying attention.

他们的职责就是持续关注，你会看到越来越多的试验，四期试验，规模更大，看看有没有什么新出现的问题，是在较小的三期试验里没暴露出来的。

It's their job to continue to pay attention and you want to see more and more trials, phase four trials, much larger trials, where you look to see is there something that's emerging that's problematic that wasn't showing up in the smaller phase three trials?

所以，我们今天就来聊聊这个。

So, we're gonna talk about that.

我们还会讨论一下长期收益的问题。

We're also gonna talk about just a longer tail on benefits.

那么，关于长期减重，我们了解多少呢？

So, what do we know about weight loss over a longer period of time?

会不会在某个时间点，个体对药物产生耐药性？

Does the individual become recalcitrant to the drug at some point?

换句话说，他们可能减重十二个月，但之后即使药物还在使用，体重却突然反弹了？

In other words, do they lose weight for twelve months but then all of a sudden they just regain in the presence of the drug still being there?

很多药物都有这种情况，不一定是在减重方面，但我们会逐渐对药效产生抗性。

There's lots of types of drugs where that's the case, not necessarily for weight loss but where we sort of get resistant to the effect of the drug.

我觉得现在我们对这些药物如何促进减重有了更深入的理解。

I think today we have a much better understanding of how the drugs promote weight loss.

所以，除了临床研究之外，我们还有更好的机制研究，能更清楚地了解实际发生了什么。

So, in addition to the clinical studies that look at this, I think we have better mechanistic studies to have more insight into what is actually happening.

上次我们讨论时，一个很大的未知问题就是我们没有真实的数据。

One of the big unknown questions when we reviewed this the last time was we just didn't have real data.

有一项研究我们能够查看，是关于停药后体重反弹的。

There was one study that we were able to look at that looked at weight regain after stopping.

所以今天我们不仅有那些初步的研究和见解，还有更多相关数据。

So today we have not just those preliminary studies and insights, but we have more data on that.

我还想补充一点，我有很多轶事证据，我相信任何开过这些药的医生都有，能说明停药后可能发生什么。

I would also just add, I had, as I'm sure any doctor who's prescribed these, I have more anecdotal evidence about what that might look like.

尼克，我觉得另一个重要方面，我过去也提到过并猜测过，就是身体成分的变化，而不仅仅是体重。

I think another big thing, Nick, that I spoke about and speculated about in the past was really around the changes in body composition and not just weight.

我记得我特别提到过，在三期临床试验中，FDA并没有要求把身体成分作为主要结果指标。

And I think I mentioned very specifically that in the phase three trials, the FDA did not require body composition as part of the primary outcomes.

所以那些研究没有做DEXA扫描，体重就是唯一的关注指标。

So, DEXA scans were not done in those studies and body weight was simply the metric of interest.

当然，因为我们开始对人们进行DEXA扫描，我们在身体成分方面看到了一些相当不同的情况。

And of course, because we started doing DEXA scans on people, we were seeing some pretty different things with respect to body composition.

但现在好消息是，我们可以从现有数据的角度来更详细地讨论这个问题了。

But the good news now is we can speak to that more from the standpoint of the data that are available.

我觉得我们还可以多谈谈运动在减重和维持体重方面的作用。

I think we can also say more about the role of exercise in both weight loss and weight maintenance.

这也是我们以前不一定有确切数据的东西。

Again, something we didn't necessarily have any hard data on before.

然后当然，我们还可以聊聊已批准药物之间的差异。

And then of course we can talk about the differences in the approved drugs.

所以我们可以多讲讲司美格鲁肽和替尔泊肽，而且我们还会谈到一种正在三期临床试验中的新药，也挺令人兴奋的。

So we can say a lot more about semaglutide and tirzepatide and we can also, we're going to talk about a new drug that's in phase three that's pretty exciting as well.

上次我们没怎么提到，但至少据我所知，现在好像很普遍的是用复方药房来配制这些药物。我们想深入聊聊这个，因为听过我们播客的人肯定都知道复方药房是什么，我们之前在另一期AMA里也讲过。

Something that wasn't really going on last time, at least to my knowledge, but seems rampant today is the use of compounding pharmacies to formulate these and we're gonna do a bit of a double click on that because people who have listened to the podcast are no doubt familiar with what compounding pharmacies are and we've covered that on a previous AMA.

我们当然特意让大家了解复方药房的好处、坏处和风险。

We obviously made a point to make sure people understand the good, bad and the ugly of compounding pharmacies.

我当然不是想说复方药房不好。

I certainly don't want to sit here and say that compounding pharmacies are bad.

这里有点“买家自负”的意思，而且它们质量参差不齐。

There's a bit of a buyer beware and they're not all created equal.

所以，了解复方药房在这些药物中扮演的角色很重要。

And so understanding what the role of the compounding pharmacy is in these drugs is important.

让我想想。

Let me think.

我想说，我们刚才提到了新药，我们会聊到那个。

I would say So we talked about new drug, we're going to talk about that.

我觉得今天另一个我想重点讲的是，了解这些药物带来的其他健康益处。

I think the other thing that I really wanna focus on today is understanding the other health benefits associated with it.

所以，如果你在刷谷歌新闻，几乎每天，至少每周，都会看到关于这类药物又有什么新好处的消息。

So, if anybody's scrolling through their Google feed, you almost can't go a day, certainly not a week without something popping up as yet another benefit of this class of drug.

就像，哦，刚发现GLP-1激动剂不仅——通常不会这么说——不仅对减肥有好处，还对治疗睡眠呼吸暂停有好处，或者对预防痴呆有好处，还有各种其他好处。

So, it's like, oh it's just been discovered that not only are GLP-one agonists and it usually won't say that, it'll say not only is good for weight loss, but it's also good for treating your sleep apnea or it's good for preventing dementia or all these other things.

所以，我想梳理一下这方面的证据，真正了解人们讨论的那五到十个其他适应症，数据有多可靠。

So, kind of want to go through the state of the evidence on that and really get a sense of the five to 10 other indications that people are talking about, how robust are the data?

所以，我就不卖关子了。

So, I'm not going to bury the lead on this.

所有这些适应症的核心问题是，这些药物的益处是否超出了我们已知的两点，也就是减轻体重和改善代谢健康及血糖控制。

The jugular question with all of these indications is going to be, is there a benefit of the drug above and beyond the two things that we know it's doing, which is reducing weight and improving metabolic health and glycemic control.

这些药物能改善其他健康指标并不令人意外，因为减轻体重和改善血糖控制总是对健康有益的。

It shouldn't be a surprise that these drugs improve other metrics of health because reducing weight and improving glycemic control always improve health.

问题在于，它们的效果是否超出了基本作用范围。

The question is, are they doing them at a level beyond the nameplate effect?

另一个三年前我们完全没讨论过的话题是，这些药物对成瘾或成瘾行为的影响。

Another topic that really we weren't talking about at all three years ago was the role that these drugs had on addictions or addictive behaviors.

最后，我想今天要谈的最后一件事是，有报道称这些药物确实可能增加自杀意念的风险。

And finally, I think the last thing I want to touch on today is reports we've heard about where these medications may indeed increase the risk of suicidal ideation.

我们稍后会讨论这个，但我觉得现在就可以直说，对于那些不想等到播客结束才听答案的人，关于这方面的证据确实很少，所以答案可能不会让人满意。

Again, we'll talk about that, but I think it's I don't have a hard time saying right now for someone who doesn't want to wait till the very end of this podcast that the answer there might not be satisfactory in terms of the paucity of evidence we have to point to that.

那么，我想既然都说了这么多，我们就一个一个地过一遍，按顺序来。

So I think with all that said, I think what we'll do is we'll just check off each one one by one and just go through it all in that order.

那我们就从第一个开始吧，也就是关于长期安全性我们了解到了什么。

And so I think let's start with the first which was what do we know more about the long term safety?

有没有新的研究或新的数据，让我们对这些药物的长期影响有了更多了解？

Has there been any new studies, any new data that's given us any insight into that long term nature of these drugs?

感谢收听今天《The Drive》的AMA抢先预览片段。

Thank you for listening to today's sneak peek AMA episode of The Drive.

如果你有兴趣收听这期AMA的完整版，可以成为我们的高级会员。

If you're interested in hearing the complete version of this AMA, you'll want to become a premium member.

对我来说，不依赖付费广告来提供所有这些内容非常重要。

It's extremely important to me to provide all of this content without relying on paid ads.

为了做到这一点，我们的工作完全依靠会员的支持。

To do this, our work is made entirely possible by our members.

作为回报，我们提供仅限会员的独家内容和福利，比免费内容更丰富。

And in return, we offer exclusive member only content and benefits above and beyond what is available for free.

所以，如果你想更深入地了解这个领域，我们的目标就是确保会员获得的回报远超订阅费用。

So if you wanna take your knowledge of this space to the next level, it's our goal to ensure members get back much more than the price of the subscription.

高级会员包含多项福利。

Premium membership includes several benefits.

首先，是全面的播客节目笔记，详细记录了我们每集讨论的每个话题、论文、人物和事物。

First, comprehensive podcast show notes that detail every topic, paper, person, and thing that we discuss in each episode.

而且大家都说，我们的节目笔记无人能比。

And the word on the street is nobody's show notes rival ours.

第二，是每月的“问我任何问题”或AMA特辑。

Second, monthly ask me anything or AMA episodes.

这些特辑包含了对订阅者问题的详细解答，通常聚焦于一个主题，旨在为会员特别感兴趣的话题提供大量清晰和详细的说明。

These episodes are comprised of detailed responses to subscriber questions typically focused on a single topic and are designed to offer a great deal of clarity and detail on topics of special interest to our members.

当然，你还可以获取这些特辑的节目笔记。

You'll also get access to the show notes for these episodes, of course.

第三，是我们的高级新闻通讯，由我们专门的研究分析团队精心制作。

Third, delivery of our premium newsletter, which is put together by our dedicated team of research analysts.

这份通讯涵盖了与长寿相关的广泛话题，比我们的免费周报提供更多细节。

This newsletter covers a wide range of topics related to longevity and provides much more detail than our free weekly newsletter.

第四，你可以访问我们的私人播客订阅源，那里有所有节目，包括AMA特辑，而且没有你现在听到的这些宣传内容。

Fourth, access to our private podcast feed that provides you with access to every episode including AMA's sans the spiel you're listening to now and in your regular podcast feed.

第五，Qualys，这是我们为会员制作的另一个播客，相当于一个精华集锦，精选了之前《The Drive》节目中的最佳片段。

Fifth, the Qualys, an additional member only podcast we put together that serves as a highlight reel featuring the best excerpts from previous episodes of the drive.

这是回顾往期节目的好方法，不用回头一集一集地听。

This is a great way to catch up on previous episodes without having to go back and listen to each one of them.

最后，还有其他陆续增加的福利。

And finally, other benefits that are added along the way.

如果你想了解更多并享受这些会员专属福利，可以访问 peterattiamd.com，然后点击订阅。

If you want to learn more and access these member only benefits, you can head over to peterattiamd.com forward slash subscribe.

你也可以在YouTube、Instagram和Twitter上找到我，账号都是Peter Attia MD。

You can also find me on YouTube, Instagram, and Twitter, all with the handle Peter Attia MD.

你也可以在Apple Podcasts或你使用的任何播客播放器上给我们留下评论。

You can also leave us review on Apple Podcasts or whatever podcast player you use.

本播客仅供一般信息参考，不构成医学、护理或其他专业医疗服务的实践，包括提供医疗建议。

This podcast is for general informational purposes only and does not constitute the practice of medicine, nursing, or other professional healthcare services, including the giving of medical advice.

不构成医患关系。

No doctor patient relationship is formed.

使用本播客中的信息和相关链接，风险由用户自行承担。

The use of this information and the materials linked to this podcast is at the user's own risk.

本播客的内容不旨在替代专业的医疗建议、诊断或治疗。

The content on this podcast is not intended to be a substitute for professional medical advice, diagnosis, or treatment.

用户不应因任何医疗状况而忽视或延迟获取医疗建议，如有此类情况，应寻求医疗专业人员的帮助。

Users should not disregard or delay in obtaining medical advice from any medical condition they have and they should seek the assistance of their healthcare professionals for any such conditions.

最后，我非常重视所有利益冲突问题。

Finally, I take all conflicts of interest very seriously.

关于我的所有披露以及我投资或提供咨询的公司，请访问 peterattiamd.com/about，我在那里保持一份最新且活跃的披露清单。

For all of my disclosures and the companies I invest in or advise, please visit peterattiamd.com slash about where I keep an up to date and active list of all disclosures.