减重处方：GLP-1药物的争议与未来系列

这是梅奥诊所谈话，一档为医生和医疗保健提供者精心策划的每周播客。

This is Mayo Clinic Talks, a curated weekly podcast for physicians and health care providers.

我是您的主持人达雷尔·丘特卡，梅奥诊所明尼苏达州罗切斯特分院的内科医生。

I'm your host, Darrell Chutka, a general internist at Mayo Clinic in Rochester, Minnesota.

被称为GLP-1受体激动剂的药物类别深受我们患者的欢迎。

The class of medications known as the GLP-one agonists is very popular with our patients.

尽管最初用于糖尿病管理，但这些药物现在常被用于减重，因为它们通常能有效减重。

Although initially indicated for management of diabetes, they're commonly being taken for weight loss, which they commonly produce.

那么这些药物应该服用多长时间？

So how long should these medications be taken?

我们能否做些什么来帮助维持这些药物带来的减重效果？

Is there anything we can do to help maintain the weight loss achieved with these drugs?

这些药物减重过程中可能出现的肌肉流失有多严重？能否将其最小化？

How significant is the muscle loss, which can occur as part of the weight loss with these medications, and can it be minimized?

最后，患者常发现更便宜的复合制剂和未经批准的版本安全性如何？

Finally, how safe are the compounded and unapproved versions of these medications patients often find much more affordable?

这些问题将是我们关于GLP-1药物的三集播客中的第三集所要探讨的内容。

These are a few of the questions we'll address in the third of three podcasts on the GLP-one medications.

我的嘉宾包括沙阿医生。

My guests include Doctor.

梅拉·沙阿博士，一位内分泌学家，以及拉乔医生。

Meera Shah, an endocrinologist, and Doctor.

塔明·拉乔博士，一位接受预防医学培训并获得肥胖症认证的医生，两人均来自梅奥诊所。

Tamin Rajo, a preventive medicine trained physician and board certified in obesity, both from the Mayo Clinic.

您正在收听梅奥诊所谈话。

You're listening to Mayo Clinic Talks.

梅拉和塔明，欢迎你们，感谢你们今天加入我们。

Meera and Tamim, welcome, and thank you for joining me today.

谢谢，达雷尔。

Thanks, Daryl.

谢谢你们邀请我们。

Thanks for having us.

这是一系列很有趣的讨论，涉及了一个非常重要的主题。

Well, this has been a fun series and covers a topic that is really important.

这些药物的一个大问题是，现在有太多患者用它们来减肥，可能导致全国许多地区糖尿病患者所需的药物供应不足。

One of the big issues with these medications has been there are now so many patients taking them for weight loss that they may exceed the supply in many areas of the country for those who need them for management of their diabetes.

对此有什么看法吗？

Any comments on that?

是的，达瑞尔，这确实是个大问题。

Yeah, Darrell, this was really an issue.

我认为这个问题在大约一两年前达到顶峰，当时人们刚开始熟悉使用GLP-1类药物减肥，并因此使用了原本用于糖尿病治疗的GLP-1药物。

I would say the peak of this issue occurred about a year or two ago when people were first starting to get familiar with using GLP ones for weight loss and were therefore using diabetes branded GLP ones.

我会称它们为‘糖尿病专用型’，因为它们最初是为糖尿病获批的，但患者却自行购买并用于减肥，这确实导致糖尿病患者难以获得所需药物。

I'll call it diabetes branded because they were approved for diabetes, but patients were sort of buying them and using them for weight loss, and that did absolutely lead to a problem with people with diabetes getting their medicines.

我很高兴地说，最近这种情况已经不那么严重了，我认为原因有几点。

I'm happy to say that more recently, that's been less of an issue for, I think, a couple of reasons.

一是减肥药物的生产商本身。

One is the manufacturers of the weight loss medicines themselves.

因此，Wegovy 和 Zepbound 的制造商大幅增加了这些药物的产量，因此对这些药物感兴趣的患者可以直接获得正确的药物，而不再使用糖尿病药物。

So the manufacturers of Wegovy and Zepbound have really upped their production of these medicines, and so patients who are interested in these medicines can just get the right thing and therefore not using diabetes medicines.

但另一方面，如今糖尿病患者可以选择如通用版利拉鲁肽等药物来管理糖尿病，因此短缺问题已不再那么严重。

But the other is that patients with diabetes now have medicines such as generic liraglutide to choose from for their management of diabetes, and so it's become less of an issue in terms of the shortages.

很高兴地说，这种情况现在已经不再发生了。

So happy to say that that's no longer really the case.

这听起来不错，因为我有一些患者确实不得不换用其他 GLP-1 药物，因为他们无法获得最初开的药。

That's good to hear, because I've had patients who literally had to switch to a different GLP-one medication because they couldn't get the one that was initially prescribed.

很高兴听到这可能已经成为过去的事了。

It's nice to hear that that's maybe a thing of the past.

在大多数情况下，这些药物能带来显著的减重效果，但仍有少数患者似乎对此类药物没有反应。

Well, medications in most cases produce substantial weight loss, but there are a few patients who don't seem to lose weight with this.

这是为什么？这种情况有多普遍？

Why is that, and how common is it?

这是个很好的问题，我们经常被问到。

That's a great question and one we get a lot.

是的，虽然这些GLP-1药物可能非常有效，但并非所有人都能实现显著的减重效果，这确实存在个体差异。

Yes, while those GLP-one medications can be incredibly effective, not everyone experiences dramatic weight loss, and that's real variability.

这种差异是生物学驱动的，而不仅仅是行为因素造成的。

That's a variability that's biologic or biologically driven, not simply behavioral.

常见吗？根据这些FDA批准药物的大规模临床试验，大约有10%到15%的患者未能达到我们所认为的临床有意义的反应——通常定义为至少在服用最大剂量数月后减掉5%的总体重。

Common, I mean, based on the trials, the large clinical trials for these FDA approved medications, about ten to fifteen percent of patients did not achieve what we would consider a clinically meaningful response or typically defined as five percent total body weight loss at least, and that's after being on the maximum dose on the medication for several months.

因此，大约五分之一的患者即使严格依从用药，减重效果也可能低于预期。

So roughly one in five patients may lose less than expected, even with excellent adherence.

临床医生了解这一点非常重要，因为这有助于设定合理预期，减少患者因未能达到至少5%的体重减轻目标而产生的不依从或羞耻感。

It is important for clinicians to know and because that helps setting expectations and reduce patients' noncompliance taboo if they do not lose appropriately or what expectedly at least 5% of their body weight.

这种情况并不罕见。

It's not uncommon.

实际上，不仅在这类药物中，在其他药物如降压药和降脂药中，患者对药物的反应也常常存在差异。

And actually, it's also not uncommon outside of this class of medications that we see variability in in how patients or people respond to different medications like antihypertensives and cholesterol lowering medications.

这些药物对不同人的效果不同，这取决于他们的生物学特征和新陈代谢。

They affect people differently, and that's based on their biology and metabolism.

我还要补充一点，达里尔，我们在减肥药物反应上看到的情况，与我们在生活方式干预或减肥手术减重方面的反应完全一致。

And I'll add, Daryl, that what we see in terms of response to weight loss medicines is exactly what we see in terms of response to lifestyle intervention for weight loss or even bariatric surgery for weight loss.

因此，无论我们使用哪种肥胖治疗方法，反应都存在明显的差异范围。

So there is this definite range of responses, no matter what modality of treatment we use for obesity.

肥胖是一个非常复杂的健康问题，多年来，甚至几十年来，其管理一直非常复杂和困难。

Obesity is such a complex health problem, and its management for years, for decades, has been very complicated and difficult.

它常常与各种不健康的行为和不良的生活方式选择相关联。

It's often associated with a variety of unhealthy behaviors and unhealthy lifestyle choices.

开减肥药是否简化了肥胖这一问题？

Does prescribing a medication to lose weight oversimplify this issue of obesity?

达里尔，这是一个非常发人深省的问题。

That's a fantastically thought provoking question, Daryl.

我认为这个问题很复杂，让我们先承认这一点。

I think it is complex, and I think let's just acknowledge that.

有趣的是，美国医学会直到2013年才将肥胖归类为一种疾病，也就是说，我们称肥胖为疾病才仅仅十二年左右。

Interestingly, obesity was only classified as a disease by the American Medical Association in 2013, So it's only been, what, twelve years since we've called obesity a disease.

我的意思是，我们真正认识到这种状况背后存在超越行为改变的病理生理机制，才仅仅过去了十二年。

By that, I mean, it's only been twelve years that we've really recognized as a pathophysiology behind this condition that's more than just behavioral changes.

所以这确实很复杂。

So it is complex.

是的。

Yes.

我们知道，某些行为会促使那些基因易感的个体发展出肥胖，但同时也存在食欲调节的紊乱。

We know that there are behaviors that predispose the already genetically predisposed individual to developing obesity, but there's also disruptions in appetite regulation.

我们处理食欲信号的方式也出现了紊乱，而这正是这些药物起效的原因——它们作用于这些生物信号，使其恢复或改变，从而使患者能够吃下我们要求他们吃的食物，而身体不再与之对抗。

There's disruptions in how we process appetite signals, and that is why these medicines work because these medicines really work on those biological signals and and sort of restore them or change them in a way that then the patient is able to eat the things that we ask them to eat without their bodies having to fight them.

这也正是为什么当他们停止用药后，情况又回到了原状。

And that's exactly why when they stop the medicines, things go back to where they were.

因此，在我看来，当这些药物有效时，几乎就是证明了我们正在治疗一种出错的生物过程，就像治疗其他任何疾病一样。

So to me, it's almost proof with these medicines when they work, it's almost proof that we are treating a biological process that has gone wrong, so much like we treat any other disease.

但我们也必须认识到，肥胖还涉及许多个体无法控制的外部因素，比如他们所处的环境、能否安全自由地在户外活动，甚至去超市购物时能负担得起哪些食物。

But we also have to, I think, appreciate that there's many external factors when it comes to obesity, things that are not necessarily in an individual's control, like the environment that they live in, like the access to being able to move safely and freely outside their home, even what types of foods they're able to afford when they go grocery shopping.

所有这些因素，无论多么微小，都会累积起来，影响一个人患肥胖症以及肥胖相关并发症的风险。

Everything, all of these things in in whatever small amount accumulate and and impact that person's risk of developing obesity as well as developing the complications of obesity.

我们之前稍微谈过，肥胖通常粗略地用BMI来定义，但我们知道，BMI为35的患者，有的代谢状况相当健康，有的则非常不健康。

We talked a little bit before about how obesity is very crudely defined by BMI, but we know that patients with a BMI of thirty five can be metabolically pretty healthy or metabolically very unhealthy.

因此，就连我们对肥胖的定义，也需要更加细致，可能比我们通常认为的要复杂得多。

And so even kind of how we define obesity, it needs to be more nuanced and is probably more complex than what we give it credit for.

所以是的，这是一种非常复杂的状况，其中一部分我们可以控制，另一部分则稍微超出我们的控制范围。

So yes, it's a very complex condition, some of which we can control and some of which are slightly outside of control.

是的。

Yeah.

我认为这正是这类药物存在争议的原因之一。

And I think that's one of the controversies with this class of drugs.

它们的作用机制非常机械。

The mechanism of action is very mechanical.

通过抑制食欲和减缓胃排空来起作用，如果它们能减少我们对高热量食物的渴望，或增强我们锻炼的意愿，那就会不一样了。

Suppressing one's appetite and decreasing gastric emptying, it'd be different if they decreased our desire for high calorie foods or increased our desire for exercising.

这将触及改变生活方式习惯的根本。

That would get at the bottom of changing lifestyle habits.

这可能会引发我们即将讨论的一些问题。

That could set some of the problems we're going to talk about.

一旦停止用药，体重往往会反弹。

You stop the medications and the weight tends to come back.

好吧，我们继续。

Well, let's move on.

在减重过程中，有时会损失相当多的肌肉质量。

As part of the weight loss that occurs, sometimes one can lose a fair amount of muscle mass as well.

这个问题有多严重？

How big of a problem is this?

这是一个非常好的、恰逢其时的问题。

That's an excellent and actually timely question there.

最近这方面的关注越来越多。

That's getting a lot of attention lately.

现在我们已经拥有了那些能够帮助我们实现两位数甚至更高比例总体重减轻的神奇药物。

Now that we have unlocked those those magic medications that would make us get to the double digit and and more in terms of of percentages of total body weight loss.

因此，我们现在有了疗效。

So now we have efficacy.

现在我们关注的是减重的质量。

Now we're looking at the quality of that weight loss.

这方面有很多研究，我们现在正在关注身体成分的变化。

There's there's a lot of research into that area, and and now we're looking at the body composition changes.

是的，我们确实观察到一定程度的瘦体重流失，尤其是肌肉流失，特别是在GLP-1激动剂治疗中。

And, yes, we do see not an insignificant degree of lean mass loss, particularly muscle mass loss, and especially with the GLP particularly with the GLP-one agonist therapy.

关于这一点的数据是一致的，针对目前获批的三种GLP-1疗法，大约25%到40%的总体重减轻来自瘦体重，其余则是脂肪质量。

The data on that has been consistent and across the for the three currently approved GLP-one therapies, and that's about 25 to 40% of the total body weight loss comes from lean mass, and the rest is fat mass.

这并非微不足道，但我们在任何极端减重方式中都会看到类似情况，比如其他极端减重手段。

Again, not that's not negligible, but we do see that with any extreme weight loss as well, so with with other modalities of of extreme weight loss.

因此，这在老年群体中尤为重要，因为他们本身已面临更高的虚弱、跌倒和骨折风险，进一步的肌肉流失会增加他们患肌肉减少症的风险，并带来其他不良后果，例如延缓某些急性疾病的康复。

So it's important in our geriatric population in particular because they are already at increased risk of frailty and falls and fractures, and further muscle mass loss puts them at more risk for sarcopenia and have more other unintended consequences, like delays their healing, for example, from certain acute illnesses.

因此，这正是目前积极研究的方向，未来将出现新一代药物，或正处于研发管线中，这些药物能够在显著减少脂肪质量的同时，保留肌肉质量。

So it's something that is being actively investigated, and now they're the future, and we're gonna talk about these later, but in the future, they're the next generation or in the pipeline, there there's research about medications that preserve muscle mass while inducing significant just fat mass loss.

我认为，初级保健医生在这方面能发挥巨大作用，他们可以密切帮助患者应对或减轻这一问题，确保患者遵循良好的饮食，特别是富含蛋白质的饮食，每天每公斤体重摄入约一至一克半的蛋白质。

I guess this is an area where primary care clinicians have a tremendous effect, where they can closely help their patients combat or mitigate this problem, where they would ensure their their patients are following a good diet, you know, a a good protein focused diet, about a gram or gram and a half per kilogram per day.

他们还应指导患者进行一些抗阻运动，即使是简单的居家运动，比如俯卧撑、引体向上、弹力带训练等。

They make sure they go over some resistance exercises with them, even the simplest ones, the home based ones, you know, push ups, pull ups, those stretch band exercises.

但我们之前已经讨论过这一点。

But, of course, we talked about this.

当然，我们还需要让专科医生、营养师和物理治疗师共同参与进来。

I I think get get getting the specialists, getting the the nutritionist on board, getting the physical therapist on board.

然后，当然，最重要的是，既然我们开了处方，就要监测体重下降的程度。

And then, of course, most importantly, because we're we're writing the prescription, is to monitor the degree of weight loss.

对于这一特定的老年群体，我建议采取缓慢而稳定的方式，避免体重急剧下降，以此降低肌肉减少症的风险，尽管仍会存在一定量的肌肉质量流失。

And in this particular geriatric population, I would go slow and steady and ensure they don't have that huge dip in weight to mitigate any risks of sarcopenia that way, although there will still be always some level of muscle mass loss.

好的。

Okay.

此外，我想说，相反，通过这些试验我们发现，这一人群的活动量也在增加。

To add to that, I would say on the contrary, we're seeing through those trials that page those this population is also getting a bit more active.

因此，他们的生活质量正在改善。

So their quality of life is improving.

所以，尽管他们正在流失肌肉，但整体感觉更好，行动也更灵活了。

So they're losing the muscle, but they're also feeling better overall and more mobile.

因此，这是这个问题的另一面。

So that's kind of the flip side of this this issue.

好的。

Okay.

好吧，我 pretty sure 我知道下一个问题的答案，但我还是想问一下。

Well, I'm pretty sure I know the answer to this next question, but I'm gonna ask it anyway.

其中一种作用机制是延缓胃排空。

One of the mechanisms of action is delayed gastric emptying.

这会影响其他药物或各种营养素的吸收吗？

Does this have any effect on impaired absorption of other medications or maybe various nutrients?

不。

No.

简短的回答是否定的。

The short answer is no.

除非胃排空延迟导致呕吐并物理性地将摄入的物质排出体外，否则它并不会真正影响吸收。

Unless the delayed gastric emptying is causing vomiting and physically expelling the things that you're taking in, it doesn't really affect absorption.

这些药物对某些患者来说成本极高，尤其是当他们自费且未被保险覆盖时。

The cost of these medications is extremely high for some patients, especially when they pay out of pocket and has not been covered by their insurance.

一些患者通过互联网购买了这些药物的复方制剂或未经批准的版本。

Some patients have obtained these medications as a compounded drug, unapproved version of these drugs often found on the Internet.

我们是否意识到这些产品可能存在质量控制问题，或者活性成分含量不稳定？

Are we aware that there could be potential problems with either quality control or maybe variable amount of active compound in these products?

简短的回答是肯定的。

The short answer is yes.

复方制剂或未经批准的GLP-1产品存在风险。

The compounded or unapproved GLP-one products are risky.

我们的许多患者在获得保险覆盖和自费支付方面面临困难，每月的负担很重。

Many of our patients struggle with coverage and needing to pay out of pocket, which is a lot on a monthly basis.

因此，许多人会使用这些缺乏质量控制的非等效成分，更不用说它们之所以能运作，是因为在药品正式短缺期间被允许存在。

So many would use these nonequivalent ingredients that lack quality control, to say the least, and they operate because they you know, they're allowed to operate in times of official shortages of medications.

它们的剂量可能不可预测，也可能存在污染问题。

They may have unpredictable dosing and may have some contamination as well.

我认为，除非出现经过验证的短缺情况（目前尚未发生），并且有合法的配制来源（我尚未见过），否则我总是建议我的患者使用经FDA批准的制剂。

I would say until there's a verified shortage, which is not the case right now, and a legitimate compounding source, which I have not seen yet, I always recommend my patients stick with an FDA approved formulations.

当成本压力真实存在时，保护患者的健康安全无疑是值得的。

And it certainly is worth protecting our patients' safety when when the the cost pressures are real.

我告诉他们，如果药物不是来自FDA批准的制造商或持证药房，且不含真正的活性成分，我们就无法保证其成分，这是不安全的。

I tell them if it's if it's not from an FDA approved manufacturer or licensed pharmacy using the real active ingredient, we can't guarantee what's in it, and that's not safe.

安慰剂效应也是真实存在的。

And the placebo placebo effect is real as well.

那么这些配制产品中到底含有什么？

So what is in those compounded products?

老实说，没人知道。

I honestly you know, nobody knows.

这谁也说不准。

It's it's anyone's guess.

好吧。

Okay.

这些药物的使用已经变得极其流行，而且看起来这并不是一时风潮。

Well, the use of these medications has gotten extremely popular, and it doesn't look like this is going to be a fad.

它们似乎会长期存在。

It looks like they're here to stay.

那么，它们会成为管理肥胖患者的标准护理的一部分吗？

So will they become part of the standard of care for managing patients with obesity?

达雷尔，你这是让我预测未来啊。

Darrell, you're asking me to predict the future here a little bit.

当然。

Sure.

你可以这么做。

You can do that.

你接受过内分泌学的训练。

You've been trained in endocrinology.

好吧，我来给你一点背景信息，因为十年前我刚开始治疗肥胖患者时，我拥有的唯一工具是减重手术和生活方式干预。

Well, I guess I'll just give you a little bit of perspective, because when I started treating patients with obesity ten years ago, the only tools I had were bariatric surgery and lifestyle intervention.

然后，逐渐出现了减肥药，正如我所说，利拉鲁肽是在十多年前获批的。

And then slowly, there were pills for weight loss, and then liraglutide, as I said, was approved just over ten years ago.

所以，当时和现在最大的区别在于，使用像司美格鲁肽和替尔泊肽这类新型GLP-1药物的患者，真的感觉到这些药物对他们产生了影响。

So the big difference between then and now is patients on these newer GLP one based medicines like semaglutide and tirzepatide really feel like it's making a difference for them.

这些患者往往在前来咨询这些长效GLP-1药物之前，已经尝试过许多不同的方法。

And these are often patients who have tried many, many different things before they come and ready to talk about one of these longer acting GLPs.

因此，我认为我的观点是，我们终于有了比以往更有效的治疗方法。

So I guess that my perspective is we finally have something that's perhaps more effective than ever before.

但我同时也相信，我们在诊室里见到的这些患者，并不是我们应该开始针对和解决肥胖问题的起点。

And I also do believe, however, that where we see patients in our offices is not really where we should start targeting or tackling this problem of obesity.

我们只是看到了那些在当下寻求帮助的人，但这是一个群体层面的问题。

We're just seeing the people who need who are asking for help at that moment in time, but this is a population level problem.

根据定义，我们有百分之四十的人口患有肥胖症，超过百分之五十的人属于超重或肥胖。

Forty percent of our population, by definition, has obesity, and over fifty percent have overweight and obesity.

所以，街上每两个人中就有一个是这样。

So that's every other person that's walking around on the street.

这并不是我们应该靠药物来解决的问题。

This is not something that we should be tackling with a medication.

我认为，这应该从公共卫生政策开始，等等，等等，从政府层面入手。

This is really, I think, something that should start with public health policy, etcetera, etcetera, things that are at the level of the government.

但对于此刻站在你面前、询问这种药物是否适合他们的患者，我总是告诉他们，这确实是我们目前最有效的方法。

But for the person that's in front of you at that moment in time who's asking about whether this medication is the appropriate thing for them, I always tell them that this is really the most effective thing we have.

它之所以有效，是因为我们相信它终于针对了那些长期以来困扰你的生物学通路，让你多年来难以减重。

And it is effective because we think it's finally targeting those biological pathways that you've been struggling with for so long that have just made it so hard for you all these years.

但使用药物也有其弊端，包括——我们稍后肯定会谈到——你可能需要终身服药的可能性。

But these are the downsides of using a medication, including you know, and and we'll talk about this, I'm sure, including potentially the fact that you may have to stay on this for the rest of your life.

我们没有停用这些药物的出口。

We don't have an off ramp for these medicines.

那么，这些药物会成为肥胖治疗的标准疗法吗？

So will these become the standard of care for obesity?

要直接回答这个问题，对于那些寻求减重以改善健康的人来说，这可能是可行的。

You To answer that question very straightforwardly, it could be could be for that individual who's looking for weight loss for health improvement.

但这是肥胖的唯一解决方案吗？

But is it really the only solution for obesity?

绝对不是。

Oh, by no means.

我认为我们必须广泛考虑各种方法，包括公共卫生政策、儿童营养等。

I think we have to look very broadly at all types of things, including public health policy, childhood nutrition, etc.

嗯，你提到了这些药物的一个大问题，那就是：我们是应该长期使用下去，还是停药并应对之后很可能出现的体重反弹？

Well, you mentioned the big issue with these, and that is, do we keep going with them indefinitely, or do we stop them and deal with their very likely weight gain that comes afterwards?

这对我们来说并不新鲜。

And this is not new for us.

对于我们这些多年来一直在管理肥胖患者的人来说，我有一些患者成功减掉了五十磅、八十磅，甚至超过一百磅，通常是通过一些他们无法长期坚持的非常规饮食。

For those of us who have been trying to manage our patients with obesity for years, I've had patients who have successful in losing fifty, eighty, even over 100 pounds, usually with some unusual diet that they can't maintain indefinitely.

尽管他们成功减掉了体重，但体重又回来了。

Although they've been successful at losing the weight, the weight comes back.

因此，我认为我们应该像过去一样，用同样的原则来使用这些药物，努力改变生活方式和不健康的行为。

So I think we need to use the same principles with these medications as we've been using in the past, work at changing the lifestyle and the unhealthy behaviors.

我同意这一点，根据我患者的亲身经历，当他们不再与自身的生理本能作斗争时，他们往往更愿意参与生活方式干预，更愿意遵循我们提供的饮食和体力活动建议。

I would agree, I'll say that anecdotally from my patients' experience, they're often much more willing to engage in lifestyle intervention, so much more willing to do the dietary intervention and the physical activity guidelines that we provide them when they are not fighting their own biology.

所以当他们已经在使用这些药物，不再感到饥饿、没有食欲冲动，也不再渴望那些高热量、高口感的食物时，突然间，你会觉得，是的，我可以。

So when they're already on these medicines and they're not hungry and they're not craving and they don't have much of an appetite for those highly palatable calorie dense foods, then suddenly, you know, yeah, I can.

我可以吃得更好。

I can eat better.

我会多吃全谷物、纤维等，因为我的身体不再不断告诉我需要别的东西。

I am gonna include more whole grains, fiber, etcetera, because my body isn't trying to tell me I I need something else.

因此，我发现将这两者结合起来效果很好，而不是像过去那样按顺序逐一进行。

So I find that it actually works quite well to do both of those things in combination as opposed to doing them sequentially, which is how we used to approach obesity.

我还发现，这些药物的高昂价格实际上对一些患者起到了积极作用，因为他们告诉我，如果我要服用这种药物并花这么多钱，我就会不惜一切代价维持住减掉的体重。

And I've also found that I think that the high cost of these drugs has actually been beneficial for some patients in that they have said to me that if I'm going to take this medication, spend this kind of money, I'm going to do whatever it takes to maintain this weight loss.

我不可能花一万美元，然后体重又立刻反弹回去。

I'm not going to spend $10,000 and have the weight come right back.

我认为这增强了他们长期坚持某些行为的动力，从而有助于维持体重的减轻。

I think this increases their motivation to do some things long term, which will result in the maintenance of their weight loss.

我想补充一点，我们可能正在走向这一趋势——这些药物将来会成为标准疗法，无论是直接还是间接地用于那些并非专门为了减肥而寻求这些药物的患者，但他们伴有心血管代谢问题，比如心力衰竭。

I'm going to add here that we may actually, not predicting the future, I think that we're getting there, that these medications are going to be the standard of care directly or maybe indirectly for patients who might be not necessarily seeking those medications for obesity, but they have an associated cardiometabolic problems like heart failure, for example.

我们看到心脏病学会正在积极倡导这些药物，因为它们看到了这些药物带来的巨大益处。

And we are seeing that the cardiology society lobbying behind these medications because of the tremendous benefits that they're seeing.

我认为，这只是我的预测：这些药物是否会成为治疗某些心血管代谢问题（如心力衰竭）的指南推荐方案。

I think, I mean, this is just my prediction, is it going to be part of the guidelines to treat certain cardiometabolic issues, like heart failure, for example.

如果是这样，那么这些药物就会成为治疗这类问题的首选，而肥胖则退居次要地位。

And if that's the case, then it becomes a go to medication as part of that problem, and obesity becomes secondary.

我们再次看到了之前提到的那些迹象，比如这些药物对非酒精性脂肪性肝炎、脂肪性肝炎、肝纤维化以及睡眠呼吸暂停的益处。

And we're seeing, again, those indications that we talked about, like the benefits in NASH, in steatohepatitis and liver fibrosis and sleep apnea.

所以它将会存在。

So it's going to be there.

它将以某种形式成为标准疗法。

It's going to be a standard of care in one shape or form or another.

是的。

Yeah.

它们将长期存在。

They're here to stay.

我认为我们甚至还不知道这些药物可能带来的所有益处。

I don't think we even know all the benefits these medications can potentially give us.

几个月前我读到一篇文章，指出使用这些药物可能会减缓阿尔茨海默病的进展。

I was reading an article a few months ago that indicated that the use of these medications may actually slow the progression of Alzheimer's disease.

如果我们有一种耐受性良好的药物，那将是非常棒的，因为目前治疗这种可怕疾病的药物效果并不理想，且副作用严重。

So that would be amazing if we had a drug that's just well tolerated because those we have to treat that terrible condition are not all that effective and terrible potential adverse effects.

那么这些药物的未来会怎样？

So what is the future of these drugs?

你认为它会走向何方？

Where do you see it going?

你对近期的前景怎么看？

What do you see in the near future?

我们会拥有更多口服药物，而不是注射剂吗？

Are we going to have more oral medications instead of injectables?

成本会下降，适应症会放宽吗？

Costs coming down, relaxing indications?

你认为这会如何发展？

Where do you see this going?

我认为以上都会实现，达里尔。

I think all of the above, Daryl.

口服药物，特别是口服GLP-1类药物，已经非常接近FDA批准了。

So the oral medications, the oral GLP ones are very close to FDA approval.

我认为今年年底前我们可能会看到口服司美格鲁肽获得FDA批准，而且根据临床试验，它的疗效至少与注射用司美格鲁肽相当。

I think we might see FDA approval by the end of the year for oral semaglutide, and we know that that has similar efficacy to injectable semaglutide at least based on the trials.

因此，肯定会有口服制剂推出，我们将在未来一年内将其应用于临床实践。

So there's certainly oral formulations coming through, which we'll be able to use in clinical practice in the next year.

我认为成本也会下降，就在不久之前，我们听说政府将降低政府保险患者用于减重的GLP药物的成本。

I do think cost is also gonna come down, and we we just heard not too long ago that the government is going to lower the cost of these GLP ones for weight loss for patients on government insurance.

这是一个巨大的进步。

So that's a huge step forward.

正如你所说，我认为这些药物的适应症正在不断扩大。

And exactly as you say, I think the indications for these drugs is just expanding.

你提到了阿尔茨海默病。

You mentioned Alzheimer's.

人们对成瘾和物质使用障碍也感兴趣。

There's interest in addictions and substance use disorder.

因此，我们完全预期将有越来越多的人符合使用这些药物的条件。

So we fully expect that the more and more people will become eligible for use of these medicines.

我认为这不仅意味着价格会下降，处方标准也可能开始改变，即 Eligibility criteria（资格标准）。

And I think that might mean that not just prices will come down, but perhaps the prescription criteria will will start to change as well, eligibility criteria.

因为目前这主要基于BMI，但很快BMI可能不再成为适应症的一部分。

Because for now, it's very much based on BMI, but soon BMI might not be part of that indications anymore.

好的。

Okay.

这是关于GLP-1激动剂用于减重的第三个也是最后一个播客。

Well, this is the third and final podcast on the topic of the GLP-one agonist medications for weight loss.

你能为我们总结一下，在过去这三个播客中我们讨论过的几个关键点吗？

Can you give us maybe a few key points that summarize the discussions we've had on these past three podcasts?

这些基于GLP-1的药物确实可以说是革命性的。

So these GLP-one based medicines are really, I would call them revolutionary.

我认为它们彻底改变了肥胖医学的格局。

I think they have really transformed the landscape of obesity medicine.

终于，我们有了真正有效的药物，帮助那些因超重而长期困扰于体重和相关健康问题的人。

Finally, we have really effective medicines for people who've struggled with their weight and their health related complications from that carrying extra weight.

因此，我们现在有了获FDA批准的减重药物，以及用于开具这些药物用于减重的FDA批准标准。

So we have FDA approved medicines for weight loss and FDA approved criteria for prescribing these medicines for weight loss.

我会建议在患者身上考虑使用这些药物，但在咨询时要为他们设定合理的期望和目标，以确保患者有良好的体验，并尽量减少这些药物可能带来的不良反应。

I would say consider these medications in the in in your patient, but do, as part of your counseling, set the right expectations and goals for them so that it is a good experience for the patient so that you minimize also any of those adverse effects that come with these medicines.

我认为我还想补充一点：从一开始就明确治疗是长期的，就像其他慢性病一样，同时管理那些通常可以耐受的潜在副作用。

And I think I would probably add that setting those expectations up front, you know, about the length of the treatment being chronic, just like any other chronic disease, management of those potential side effects that are generally tolerable.

此外，还要关注长期管理，这必然需要结合生活方式的改变，而这些改变在开始用药前一直难以实施，因为它们的效果微乎其微。

And and then just being mindful of the long term management that would certainly require integrating the lifestyle modifications that have long been challenging before starting the medication because of their minimal effects.

但如今，随着活动能力的改善、食物渴望的减少以及饮食习惯的提升，这将带来一种终身的、更健康的生活方式改变，涵盖饮食和体力活动。

But now with hopefully better mobility and without with the with the decreased food noise and the improved eating habits, this would be a lifelong change for a better lifestyle dietary and physical activity lifestyle.

我们一直在与谢米拉医生和拉乔医生讨论GLP-1药物未来的争议。

We've been discussing controversies in the future of the GLP-one medications with Doctor.

谢米拉医生和拉乔医生均来自梅奥诊所内分泌科。

Meera Shah and Doctor.

谢米拉医生和拉乔医生均来自梅奥诊所内分泌科。

Tamim Rajo, both from the Division of Endocrinology at the Mayo Clinic.

米拉和塔明，非常感谢你们今天与我们分享你们的专业见解。

Meera and Tamim, thank you so much for sharing your expertise with us today.

这个话题真有趣。

This has been a fun topic.

谢谢，达里尔。

Thanks, Daryl.

谢谢你们邀请我们。

Thanks for having us.

您现在可以在梅奥诊所谈话播客中收听数百个为初级保健提供者开发的医学话题。

You can now listen to several 100 different medical topics developed for primary care providers on Mayo Clinic Talks podcasts.

请访问 ce.mayo.edu 或您最喜欢的播客应用查找这些内容。

Find them at ce.mayo.edu or your favorite podcasting app.

如果您喜欢梅奥诊所谈话播客，请关注我们。

If you've enjoyed Mayo Clinic Talks podcasts, please follow us.

我们很荣幸能有您作为听众，并邀请您下周再次收听。

We're honored to have you as a listener and invite you to tune in again next week.

保重。

Stay well.