减肥神药GLP-1停药后，反弹回来的体重几乎全是脂肪？身体可能比吃药前更糟｜科学60秒

人类对“万能药”的幻想由来已久。从中世纪的炼金术到 20 世纪的青霉素，每一种被寄予厚望的药物背后，都藏着一段或被低估、或被高估的故事。如今，一类名为 GLP-1 的药物正在重演这套剧本：它最初只是用来控制血糖的糖尿病药物，却意外被证明有极佳的减重效果。近几年来，科学家们陆续发现它可能对心血管、成瘾、慢性炎症乃至生殖健康产生影响。不过，问题随之而来，它真的能担起这些有关疗愈、健康，甚至延年益寿的期待吗？

2026 年 3 月初，美国食品和药品管理局（FDA）向诺和泰（Ozempic）与诺和盈（Wegovy）的制造商诺和诺德（Novo Nordisk）发出一封警告信，指控该公司未能依法披露与这些药物相关的潜在风险。

具体而言，三名服用司美格鲁肽（semaglutide，Ozempic 与 Wegovy 的活性成分）的患者死亡事件，未被诺和诺德按照法定时限（15 日内）报告或妥善追踪，其中还包括一例自杀。FDA 强调，这并不意味着药物本身导致了上述死亡，问题在于安全信息的报告流程出现了“严重违规”。

司美格鲁肽属于一类被统称为 GLP-1 受体激动剂（GLP-1 receptor agonists）的药物。从 2 型糖尿病到肥胖症治疗，它们近年来成为制药界炙手可热的新宠，被认为具有远远超出血糖与体重管理之外的潜在效益。而这股热潮也带来了另一面：大量未获 FDA 批准的“仿制 GLP-1”产品正在涌入市场。

GLP-1 这一缩写来自“胰高血糖素样肽-1”（glucagon-like peptide-1），这是一种人体本就会分泌的天然激素。这种激素能同时对血糖和体重起效，关键在于其自身的双重作用机制：一方面，它能促进胰岛素分泌，从而降低血糖，这也是它最早被开发为糖尿病药物的原因；另一方面，研究者后来注意到，服用该类药物的患者普遍出现进食量下降的现象。进一步研究表明，GLP-1 同时影响饱腹感的调节，使人更快、更持久地产生“吃饱了”的感觉，进食随之减少，体重也随之下降。

我们熟悉的几款“明星药物”，比如前面提到的 Ozempic 与 Wegovy，都是通过模拟这种激素发挥作用。它们最初均作为 2 型糖尿病治疗药物上市，自 2021 年 Wegovy 获批用于减重以来，整个 GLP-1 家族迅速扩张：替尔泊肽（tirzepatide，商品名穆峰达/Mounjaro、Zepbound）、利拉鲁肽（liraglutide）、度拉糖肽（dulaglutide）……虽然名目繁多，但它们都属于广义的肠促胰素类药物家族，通过模拟体内天然激素来调控血糖与食欲。

不过，人体自然分泌的 GLP-1 属于短效激素，体内特定的酶会迅速将其分解。而药物版本的 GLP-1 经过专门的分子改造，能够抵抗这种快速降解，在体内维持较长的活性时间。以司美格鲁肽为例，打一针就能在体内发挥作用，持续时间约一周。

近几个月，围绕一类被称为“仿制 GLP-1”或“复合 GLP-1”的产品，争议持续升温。

要理解这一现象，首先需要明白什么是“复合药物”（compounded drug）。简单来说，复合药物是由“复合药房”（compounding pharmacy）根据具体临床需求定制生产的药品。它们的用途相当多样。例如，无法吞咽口服药物的患者可能需要将药物制成乳膏或静脉注射液；儿童可能需要更低剂量；甚至对于宠物和动物园的动物，也常常依靠复合药房为其特别调配药方。

在医疗体系中，复合药房确实承担着不可替代的角色。但需要注意的是，任何复合药物都未经过 FDA 批准：它们既没有接受标准化的安全性评估，也没经过有效性审查。

复合 GLP-1 的故事，要追溯至该类药物刚开始在市场上爆红的时期。当时，Ozempic 在糖尿病治疗之外被大量“超适应症使用”（off-label use），应用于减重，加之众多名人公开使用，进一步推高了需求。2021 年，Wegovy 正式获批用于减重，市场需求随即彻底引爆，并于 2022 年陷入全面短缺。随后，替尔泊肽也被列入短缺名单。

按照美国的药品监管规则，当某种药物处于官方认定的短缺状态时，复合药房就被授予临时生产权限，以填补市场供应的缺口。在这一阶段，复合药房确实扮演了缓解“用药难”问题的重要角色。

时间来到 2024 年末，替尔泊肽从短缺名单中被移除，司美格鲁肽也于 2025 年随之恢复供应，按理说，复合药房此时本应停止生产这些药物。事实却并非如此。

许多复合药房通过两条路径继续运营。其一，规则允许复合药房为存在特殊剂量需求的患者继续配制药物。由于 Ozempic 和 Wegovy 的注射笔为预填充剂型，剂量阶梯固定，当患者需要介于两档之间的剂量时，复合药房便有理由介入填补空缺。其二，部分复合药房开始在原有配方中加入所谓添加剂，打造定制版 GLP-1。这些添加剂的宣称功能颇具吸引力：有的声称可以缓解 GLP-1 减重过程中常见的肌肉流失，有的则声称能减轻该类药物易引发的恶心和胃肠道反应。然而，依旧没有一种“添加剂”经过了安全性或有效性的临床验证。

对消费者而言，复合 GLP-1 最直接的吸引力在于价格。复合药房使用的活性成分原料通常更为廉价，最终产品的市场售价也因此远低于官方品牌药物。此外，对于确有非标准剂量需求的患者来说，复合药物在剂量调整上更具灵活性。这些都构成了它真实存在的市场需求，也使其得以在监管夹缝中灵活游走。

诺和诺德与礼来（Eli Lilly）的相关药物仍处于专利保护期内，理论上不允许任何完整意义上的仿制版本流通。药企当然不会坐视不管。2026 年 2 月，诺和诺德将远程医疗公司 Hims & Hers 告上法庭，指控这一美国最大的复合 GLP-1 销售平台之一，将自家复合产品作为首选药物，进行误导性营销，并涉嫌仿冒。该诉讼随后又因双方达成合作协议而撤回，这场风波暂时未能进入司法判决阶段。

真正让 GLP-1 类药物从“糖尿病-减重双适应症”跃升为科研热点的，是过去几年间，关于其潜在成瘾治疗效果的大量轶事性报告。许多服药者反映，他们欲望的消退远不止于食物，对零食的兴趣减弱，对酒精、尼古丁的渴求也明显下降，甚至连咬指甲、抠手等强迫性小习惯也悄悄消退。

这一系列现象迅速引起了成瘾研究者的注意。脑科学早已揭示，食物奖赏通路与成瘾行为的神经回路高度重叠。既然 GLP-1 能够调控前者，那么它是否同样能影响后者？这一假设，随即催生了一波密集的成瘾医学研究。

一项 2026 年 3 月发表于《英国医学期刊》（The BMJ）的大规模流行病学研究为这一假设提供了迄今为止最有力的证据。这项研究由美国华盛顿大学医学院（University of Washington School of Medicine）的临床流行病学家齐亚德·阿里（Ziyad Al-Aly）领衔，团队分析了超过 60 万名罹患 2 型糖尿病的美国退伍军人电子健康记录。

研究人员将服用 GLP-1 类药物的患者与服用另一类糖尿病药物 SGLT-2 抑制剂的患者进行对比，结果发现，在原本无任何物质使用障碍的人群中，GLP-1 的使用与酒精、尼古丁、阿片类、可卡因、大麻在内的几乎所有类别物质使用障碍的发生风险下降相关，阿片类相关障碍的风险下降最为显著，约为 25%。而在原本已存在成瘾问题的人群中，与药物滥用相关的死亡率下降了约 50%，急诊就诊次数下降 30%，过量用药事件下降近 40%。

此外，研究还观察到，GLP-1 使用者的自杀意念较对照组下降了 25%。这一发现，恰好与监管机构早期对其潜在自杀风险的担忧出现了冲突。这一发现迅速在成瘾医学领域激起广泛关注。例如，一些阿片类药物成瘾的治疗研究者正在尝试将 GLP-1 与现有治疗方案结合：传统疗法往往需要使用某种阿片类替代药物进行管理戒断，而 GLP-1 的加入或许可以减轻对替代药物的依赖。当然，相关研究仍处于早期阶段，但这片“意外发现的新大陆”正变得越来越令人着迷。

除成瘾治疗之外，GLP-1 的潜在获益版图还在持续扩展。Wegovy 已被 FDA 正式批准用于降低心血管事件风险，这是其首个超出血糖与体重之外的明确适应症。研究者也正在探索其在生殖健康领域的应用，甚至包括对多内分泌代谢卵巢综合征（PMOS，原名“多囊卵巢综合征”）相关代谢问题的潜在改善。更引人注目的是，越来越多的证据提示，GLP-1 还可能具有抗炎作用。若这一机制得到证实，相关治疗的应用范围将进一步扩展至各类慢性炎症性疾病。

在硬币的另一面，GLP-1 远非万能。它们在临床上虽已使用数十年，但大规模、长周期、广人群的使用历史相对有限，长期效应仍是科学界悬而未决的问题。

2026 年 3 月，美国骨科医师学会（AAOS）年会上发布的一项研究，对约 14.6 万名 2 型糖尿病合并肥胖患者展开了五年回顾性队列研究。分析发现，使用 GLP-1 受体激动剂者发生骨质疏松的相对风险较未使用者高出约 30%（4.1% vs. 3.2%），同时，痛风、骨软化症的发病率也略有上升。研究者推测……[查看全文]

Weight loss was just the beginning: How the GLP-1 story is evolving

The drugs are part of a broader class of medicine known as GLP-1s that have grown wildly popular for everything from type 2 diabetes to weight loss and are increasingly seen as having potential benefits far beyond those two conditions. The popularity of these drugs has led to a sea of GLP-1 offerings flooding the market—not all of them FDA-approved.

We sat down with Lauren Young, an associate editor covering health and medicine for Scientific American to talk about where GLP-1s go from here.

Pierre-Louis: Thank you for being here, Lauren.

Lauren Young: Thanks so much for having me.

Pierre-Louis: So at a basic level, what is a GLP-1?

Young: Right, so GLP-1 drugs, these are the drugs that you’ve probably heard with those, like, fun advertisement chimes. They’re sold as Wegovy and Ozempic—that is the brand name for the active ingredient semaglutide. And then you’ll probably have also heard of Zepbound and Mounjaro, which are the brand name for tirzepatide. And so these were originally type 2 diabetes treatments, and now they have since moved on to become weight-loss treatments. And the reason why they’re so effective is because they mimic a hormone in the body called GLP-1, glucagonlike peptide 1—fun name.

And so what this hormone does is it, essentially kick-starts insulin production, so that’s why it makes a really great type 2 diabetes medication. But over time researchers also noticed that, “Hey, it looks like people are eating less on this drug.” And they found out that it also influences satiety levels, people feel fuller faster, and you eat less and therefore lose weight. So that’s essentially how the hormone and also the drug works ’cause the drug essentially mimics that hormone.

Pierre-Louis: And my understanding is, is that, in general, in our bodies, GLP-1s are kind of short-acting. But with the drug, they kind of hang out for longer.

Young: Exactly. Yes, yes. So these drug manufacturers have essentially crafted them to withstand and stay in the body longer because there’s enzymes in the body that break down the hormone at much faster rates, so they can last in the body for—stay active, essentially, for about a week.

Pierre-Louis: So there’s been this big kind of tension brewing in recent months about the rise of what we might call imitation GLP-1s, like, the compounded versions. Can you tell me: What is a compounded drug?

Young: Right, so a compounded drug, these are produced by compounded pharmacies. So compounded pharmacies essentially create, like, bespoke medicines for individual clinical use. So people who can’t take an oral medication, for instance, might need that medication transformed into a cream or an IV drip or something like that, or kids, for instance, might need a lower dose. Same with, like, pets and zoo animals, they also sometimes take compounded medications ’cause they, you know, need a specialized recipe for, you know, specific medications.

Pierre-Louis: So, for example, I had an ankle injury a couple years back ...

Young: Yeah.

Pierre-Louis: And my doctor prescribed, like, a bespoke anti-inflammatory lotion for me to put on it ...

Young: Right.

Pierre-Louis: And that was sent to me by a, a compounder.

Young: Yeah, yeah, that’s a, a perfect example of what a compounded drug is. So these compounded pharmacies do fill an important need. But it’s also important to note that no compounded drug is FDA-approved, so that means they aren’t tested or reviewed for safety or effectiveness.

Pierre-Louis: Can you talk a bit about the role that compounding pharmacies have been playing with GLP-1s?

Young: So the story of the compounded GLP-1s goes back to when these drugs first spiked in popularity for a multitude of reasons. Ozempic, for instance, was being used off-label quite often; a lot of celebrities were using it. And these medications are also originally for diabetes. But then in 2021 [semaglutide] became approved for weight loss.

That essentially exploded the popularity of these drugs, and they went under shortage in 2022. Subsequently, another popular drug, tirzepatide, which is [now] sold as Zepbound and Mounjaro, also went under shortage.

So when a drug goes under shortage, that essentially gives authority to these compounders to start producing them, you know, to fill in these access gaps. So in many ways, these compounding pharmacies filled in a really important void.

Pierre-Louis: But then they stopped being under shortage, but the compounders still kept making them, right?

Young: Yeah, tirzepatide got lifted off of the shortage list in, I think, late 2024, and then semaglutide followed in 2025. And so how do these drugs essentially continue to be compounded? Well, the way that a lot of these companies are getting around it is, one, that they’re allowed to be compounded if people need a specific dosage. So, for instance, the Ozempic and Wegovy pens are prefilled, so if an individual, for instance, needs something higher or lower, these compounders can fill in that gap.

Additionally, a lot of these companies are putting, quote, unquote, “additives” and creating custom versions of these drugs. And these additives are very interesting. Some of ’em are—claim to help with potential muscle loss ’cause that is something that has been noted with the GLP-1 weight-loss drugs. Another thing, too, is these drugs, the GLP-1s, have a lot of nausea and gastrointestinal side effects, so some of these, quote, unquote, “additives” are claiming to help with those effects. None of these additives have been tested for safety or effectiveness. But that’s how they’re getting around still continuing to compound these drugs.

Pierre-Louis: And as a consumer, what’s the benefit of going through a compounder versus, you know, a pharmaceutical company’s official version?

Young: Oftentimes these compounders are selling these drugs at vastly lower market rates than the official brand versions of the drugs, and this is because the active ingredients they’re getting are often cheaper. So that’s one of the primary reasons, is the cost. And then, you know, with people who do need different dosages, that maybe they’re in between the tiers that are designated in these pens. So there are benefits, for sure.

Pierre-Louis: In February, Novo Nordisk, the maker of Ozempic and Wegovy, sued one of the largest sellers of the compounded versions, the telehealth company Hims [&] Hers, and then dropped the lawsuit. Can you talk a bit about the origins of that lawsuit?

Young: Right, so Novo Nordisk essentially sued Hims & Hers because they were saying that, “Hey, you’re mismarketing your compounded GLP-1s as essentially a first go-to drug instead of our drug.” They also were alleging them to be, like, “copycats.” And these drugs under Novo Nordisk and similarly Eli Lilly, they’re still under patent ...

Pierre-Louis: Mm-hmm.

Young: So you can’t just create a full copycat medication of these drugs. That was, like, the main impetus of the lawsuit.

Pierre-Louis: But they’ve since dropped it.

Young: Right, yes, they have dropped the lawsuit as of last week.

Pierre-Louis: So, you know, Ozempic [is] technically a diabetes drug, and Wegovy shares the same main ingredient as Ozempic, semaglutide, but at higher doses.

Young: Mm-hmm.

Pierre-Louis: And since 2021, when Wegovy was approved for weight loss, we’ve seen sort of this explosion in GLP-1s—there’s tirzepatide, liraglutide, dulaglutide.

Young: [Laughs.] It’s a game, like, which of these medications are actually a real thing ’cause it’s just fun word scramble all the time. [Laughs.]

Pierre-Louis: And over the past, you know, 15, 20 years, these drugs have been seen as useful for type 2 diabetes and weight loss. There’s growing research that GLP-1s can be useful for other things, like alcohol use disorder.

Young: Mm-hmm.

Pierre-Louis: Can you talk about some of those benefits?

Young: Yeah, there’s been, actually, several studies that have come out on the addiction side of GLP-1s. So it’s interesting because it all stems from kind of a flood of anecdotal reports from people just saying, like, “You know, I’m taking these drugs, and I’m noticing not only are some of my—you know, like, my satiety levels are different; I’m not craving, you know, snacks and food as much. But I’m also not, you know, itching to, like, pick my nails anymore. I’m not craving, like, drinks or alcohol anymore. I’m not craving nicotine anymore.”

And so this really set off, like, a wave of research in the addiction space of, you know, scientists thinking like, “Okay, you know, we know that food reward pathways are overlapped, and we know that, oftentimes, that’s what we see in addiction, too. Maybe there’s something here for a potential treatment.”

Just recently there was a huge study in the [Veterans] Affairs health-care system. They, you know, collected data from, like, over 600,000 veterans ...

Pierre-Louis: Mm-hmm.

Young: So, you know, caveating those are mostly white, male, older, you know, individuals, but it was really striking because these are also people with type 2 diabetes, and they were evaluating a variety of different GLP-1 uses. And they noticed that using a GLP-1 essentially cut down the risk of developing a substance use disorder.

And these were all different types of substance use disorders: they looked at cannabis use disorder, opioid use disorder, alcohol use disorder, and not only that—they also looked at people who already had a substance use disorder, and they found there that it cut down things like drug-related mortality by, I think, as much as 50 percent. And that’s an impressive reduction.

And so it’s very attractive to people like addiction researchers. I, you know, spoke to, for instance, a researcher who’s doing opioid-addiction treatment. She’s doing trials right now looking at GLP-1 use, potentially, to offset the use of some of the other treatments that—’cause you have to take an opioid in order to be treated for the disorder, so, you know, maybe coupling it could be appealing. But there’s a lot still to learn, but it’s a really fascinating space, for sure.

Pierre-Louis: Are there other sort of unexpected potential benefits that they’re seeing from these drugs?

Young: We already know that Wegovy, for instance, has been approved for cardiovascular-risk reduction, so we’ve seen that. I’ve been personally really interested in the reproductive-health space. And they’re also finding that the use of GLP-1s might also reduce inflammation, and that’ll—obviously could open up, you know, a variety of different treatments for so many different types of diseases. There’s a lot of interesting different avenues of research going on.

Pierre-Louis: That said, the flip side, you know, these drugs are not a panacea, and we are finding some things that are maybe concerning.

Young: Yeah, so these drugs, while they have been around for decades, more and more people are using them. We really don’t know the long-term ramifications of these drugs. Just recently there was a, a big analysis, and I think that found that GLP-1 drugs were linked to a higher risk of skeletal disorders, so things like osteoporosis.

Pierre-Louis: Mm-hmm.

Young: And we’ve also seen that GLP-1s might be related to a loss in muscle or lean mass. That’s been, like, another big, concerning thing among clinicians ’cause when you think about weight loss, whether it’s through a GLP-1 drug, exercise, diet or something like malnutrition, you’re losing all different, quote, unquote, “types” of weight. So yes, you’re losing fat, but you’re also losing things like muscle and bone mass, and those things are important, especially...[full transcript]