在哈利法克斯市中心的一家婚纱店里，贝弗莉·史密斯正在试穿婚纱，但有个问题：自从开始使用GLP-1药物以来，她的体重正在快速下降。
At a bridal shop in downtown Halifax, Beverley Smith is trying on wedding dresses, but there’s a catch: She's rapidly losing weight since starting a GLP-1.
这位32岁的女性已经反复停用和重新使用过几种这类热门药物，以控制体重增加以及与多内分泌代谢性卵巢综合征（PMOS）相关的其他副作用，但她决定在明年夏天结婚前认真对待自己的健康。
The 32-year-old has already gone on and off several types of these popular medications to manage weight gain and other side-effects linked to polyendocrine metabolic ovarian syndrome (PMOS), but decided to get serious about her health before getting married next summer.
自三月份开始使用替尔泊肽以来，她已经减重超过30磅，并表示相关症状——比如关节疼痛——也有所改善。
She’s lost more than 30 pounds since starting the drug tirzepatide back in March, and says related symptoms — like joint pain — have improved as well.
现在，她正在问一个与全世界数百万GLP-1使用者相同的问题：是否有可能在某一天停用这种让生活变得更好的药物？
Now she’s asking the same question as millions of GLP-1 users around the world: Is it possible to one day stop taking the drug that’s changed life for the better?
“当你停药的时候……你是逐渐减量还是突然停掉？”史密斯想知道。“从长远来看，这到底会是什么样子？”随着这些重磅药物人气暴涨，越来越多的人超适应症使用它们来短期减重，科学家们也在努力寻找答案。
"When you are going off it…. do you taper off of it or do you stop abruptly?" Smith wondered. "What is this really going to look like in the long term?" As these blockbuster drugs explode in popularity, with more people using them off-label for short-term weight loss, scientists are also striving to find an answer.
“这是一个需要研究的现实世界情况，”宾夕法尼亚大学的临床科学家托马斯·梁博士说，他正是从事这项研究的科研人员之一。
"This is a real-world situation that needs to be studied," said Dr. Thomas Leung, a clinician-scientist at the University of Pennsylvania, who’s among the researchers doing exactly that.
微剂量、药物循环及更多 GLP-1药物的作用机制是抑制血糖、控制食欲和减缓胃排空，这一切都是通过模仿其同名激素——胰高血糖素样肽-1——来实现的，该激素在你进食后释放。
Microdosing, drug cycling and more GLP-1 drugs work by suppressing blood sugar, controlling appetite and slowing stomach emptying, all by mimicking their namesake hormone, glucagon-like peptide-1, which is released after you eat.
300万加拿大人使用GLP-1药物。调查称这正在改变他们的食欲——以及习惯 第二意见 每个人都应该使用GLP-1吗？科学对癌症预防和其他益处的真正说法 虽然这些药物直到过去几年才进入大众视野——在名人代言的推动下，随后进入主流——但它们已经存在了二十多年。
3 million Canadians use GLP-1 drugs. Survey says that's changing their appetites — and habits Second Opinion Should everyone be on GLP-1s? What the science really tells us about cancer prevention and other benefits While these medications only became part of the zeitgeist in the last few years — driven by celebrity endorsements, before hitting the mainstream — they’ve been around for more than two decades.
最早的形式经过研究和批准，用于治疗2型糖尿病。后来，又出现了用于长期体重管理的选择。相对较新的是人们使用这些药物的多种方式，而且往往是在极少医疗监督的情况下。
The earliest forms were studied and approved to treat Type 2 diabetes. Later, options arrived for chronic weight management. What’s relatively new is the myriad ways people are using these medications, often with minimal medical supervision.
许多患者——或者正如一些制药商现在所称的“客户”——把GLP-1类药物当作溜溜球式节食来对待，而不是长期服用以管理慢性健康问题。
Many patients — or as some drugmakers now call them, "customers" — are treating GLP-1s like a yo-yo diet rather than taking them long term to manage chronic health conditions.
如今通过网上药店获取这些药物越来越容易。而且，相比注射剂，药片形式正变得越来越普及。（虽然尚未在加拿大上市，但有一种药片形式的司美格鲁肽——该药物最广为人知的品牌名是Ozempic——已在美国获批，来自制药商诺和诺德，同时还有礼来公司的一种口服版orforglipron。）翻看社交媒体，很容易找到各种短期用法，从健美运动员在健身计划之外轮换使用不同类型的GLP-1类药物（以及类固醇），到女性断断续续“微量服用”这些药物以控制更年期体重增加，再到新郎新娘在婚礼前短期用药快速减重。
They’re ever easier to get through online pharmacies. And pill forms, versus injections, are becoming more accessible. (Though not yet available in Canada, there is a pill-based form of semaglutide — the drug best known by the brand name Ozempic — already approved in the U.S. from drugmaker Novo Nordisk, alongside a pill version of orforglipron from Eli Lilly.) Scroll through social media and it’s easy to find a range of short-term uses, from bodybuilders cycling through different types of GLP-1s (and steroids, too) alongside their gym routines to women "microdosing" the drugs off and on to manage menopausal weight gain to brides and grooms doing quick stints to lose weight before their wedding day.
丹麦一个研究团队最近的一项研究考察了司美格鲁肽用于肥胖症的情况，发现大约一半的成年人在短短12个月内就停止了治疗。
One recent study from a Danish research team looked at the use of semaglutide for obesity and found roughly half of adults stopped treatment within just 12 months.
停停用用的方式可能妨碍减重。宾夕法尼亚大学研究员梁医生近年来在自己的社交圈里注意到了这一趋势，因为他有越来越多的朋友和同事想尝试GLP-1类药物，只是为了减掉几磅体重。
Stop-and-start approach could hinder weight loss It’s a trend Dr. Leung, the researcher from the University of Pennsylvania, noticed in his own social circle in recent years, as more of his friends and colleagues wanted to try GLP-1s just to drop a few pounds.
有些人谈到想在度假前减重，或者为了在Instagram上好看，或者只是为了感觉更健康。共同点是什么？就是想用上这些药，然后尽快停掉。
Some talked about wanting to shed weight before a vacation or to look good on Instagram or just to feel healthier. The common thread? A desire to go on the meds, then get off them as fast as possible.
梁说：“以前没人真正研究过，当你模拟人类的实际行为——也就是开始和停止服用这些药物时——会发生什么。所以我们想，好吧，显然不能在人类身上测试这个。但我们可以试着在小鼠身上做。”
"No one had really studied what happens when you model what human behaviour is, which is starting and stopping these drugs," Leung said. "So we’re like, OK, well, obviously you can’t test this in humans.
通用版奥西金（Ozempic）现在全国各地大约是每月100加元。加拿大人开始关注 加拿大卫生部批准诺和诺德奥西金的首个通用版本 梁和他的研究团队确实这么做了，发现让超重小鼠周期性使用GLP-1类药物，似乎会让药物效果随时间减弱。每两周开始和停止一次用药的小鼠，减重效果不如在长达数月的研究期间持续使用GLP-1类药物的小鼠。
But we can try to do this in mice." Generic Ozempic is now about $100 a month across the country. Canadians are taking note Health Canada approves 1st generic version of Novo Nordisk's Ozempic Leung and his research team did exactly that, and found cycling overweight mice through GLP-1 use seemed to make the drugs less effective over time. Mice who started and stopped the drugs every two weeks struggled to lose weight compared to mice who stayed on GLP-1s for the entire months-long study.
即使在研究结束时连续使用了两个月药物，周期性用药组的体重仍重20%。
Even after two months of consistent use at the end of the study period, the drug-cycling group remained 20 per cent heavier.
如果小鼠身上会出现这种情况，梁开始想：在人类患者停止和开始服用这些改变身体的药物时，体内到底发生了什么？
If that was happening to mice, Leung started to wonder: What’s actually happening inside the bodies of human patients stopping and starting these body-changing drugs?
“买者自负”地使用GLP-1类药物治疗非适应症 伯灵顿万顿体重与糖尿病管理诊所的肖恩·万顿医生在自己的患者身上经常看到这种情况。
'Buyer beware' when using GLP-1s off-label Dr. Sean Wharton sees that regularly in his own patients at the Wharton Medical Clinic for weight and diabetes management in Burlington, Ont.
“人们经常将其用于非适应症。也许他们在互联网或脸书上听说了什么。如果他们这样用于非适应症，那么就是……买者自负，”他说。
"People are using it off-label often. Maybe they heard about something on the internet or on Facebook. And if they're using it in this manner off-label, then it’s … buyer beware," he said.
“因为我不知道可能会发生什么类型的负面影响。可能主要是正面影响，没有负面影响，但我们目前还不确切知道。” 研究综述：停用减肥药后体重反弹、心脏健康恶化 加拿大卫生部警告假冒或未经授权的GLP-1类药物 万顿强调，这一不断壮大的药物类别作为肥胖症的长期治疗有明确益处，而肥胖症若不治疗，会对炎症和心血管疾病等其他健康问题产生危险的多米诺骨牌效应。
"Because I don't know what type of negative aspects could potentially happen. There could be mainly positive and no negative aspects, but we don't exactly know yet." People regained weight, worsened heart health after stopping weight loss drugs: review Health Canada warns about fake or unauthorized versions of GLP-1 drugs Wharton stressed this growing class of drugs has clear benefits as a long-term treatment for obesity, which has a dangerous domino effect on other health issues, like inflammation and cardiovascular disease, when left untreated.
研究还表明，GLP-1类药物可能有助于抑制物质使用障碍、减轻睡眠呼吸暂停的严重程度，甚至降低癌症风险。
Research also suggests GLP-1s may help curb substance use disorders, cut the severity of sleep apnea or even reduce cancer risk.
然而，正如沃顿所称，这些药物正日益从经过验证的治疗手段转向“美容医学领域”，用于短期使用。他表示，当患者匆忙停药时，获益很可能会随之消失。
Yet increasingly, these drugs are moving from tested treatment into what Wharton calls the "aesthetic medicine space" for short-term use. And he says the benefits likely vanish when patients rush back off these drugs.
“如果减重是你的代谢状况——比如心力衰竭、高血压——好转的原因，那么体重反弹通常意味着血压会回升。”
"If losing the weight was the reason why your metabolic condition — like your heart failure, your high blood pressure — got better, then regaining the weight usually means that that blood pressure is going to go back up."
视频 Ozempic使用、蛋白质摄入最大化推高乳清蛋白价格 我们知道垃圾食品不健康，但科学家正试图弄清它是否也损害大脑 去年，一项主要研究综述得出结论，这类健康影响的“幅度和一致性”“凸显了[GLP-1]停药的生理后果”。根据该研究团队的说法，一个关键需求是制定治疗指南，以同时解决如何使用这些药物的问题。停用这些药物的最佳方式是什么？
Video Ozempic use, protein-maxxing driving up whey protein prices We know junk food isn't healthy, but scientists are trying to determine if it's also bad for our brains Last year, one major research review concluded that the "magnitude and consistency" of these kinds of health effects "underscore the physiological consequences of [GLP-1] discontinuation." A key need, according to that research team, was treatment guidelines to also address how to using the drugs. What's the best way to go off these drugs?
GLP-1先驱丹尼尔·德鲁克博士赞同这种方法。在多伦多，他正帮助牵头一项随机对照试验——医疗研究的金标准——以找出人们安全停用他帮助推向大众的这些药物的最佳方式。
GLP-1 pioneer Dr. Daniel Drucker agrees with that approach. In Toronto, he’s helping lead a randomized controlled trial — the gold standard of health-care research — to find out the best way for people to safely stop taking the drugs that he helped bring to the masses.
研究团队成员包括沃顿和德鲁克的同事、内分泌学家卡罗琳·克雷默博士，正在招募患者进行为期16周的研究，期间他们将定期进行血液检查和其他指标测定，以评估缓慢减量停用GLP-1类药物与突然停药的影响。
The research team, which includes Wharton and Drucker’s colleague and fellow endocrinologist Dr. Caroline Kramer, is recruiting patients for a 16-week-long study period where they’ll go through regular bloodwork and other metrics to gauge the impact of slowly tapering off a GLP-1 compared to abruptly stopping.
“我们试图回答一个非常简单的问题：如果有人想知道，他们能否停用GLP-1药物，最佳方式是什么？”德鲁克在西奈山医院的一间实验室里对加拿大广播公司（CBC）新闻表示。
"We’re trying to answer a very simple question: If someone wants to know, can they come off the GLP-1 medicines, what is the best way to do it?" Drucker told CBC News inside a lab at Mount Sinai Hospital.
德鲁克说：“制药公司并不擅长研究如何停用他们的药物，但我们需要回答这个问题。”德鲁克是认为GLP-1类药物具有巨大潜力、能以此减少肥胖严重影响的人之一。肥胖是一场如此广泛的公共卫生危机，以至于就在今年，世界卫生组织发布了有史以来第一份从儿童期开始管理肥胖的指南。
"Pharmaceutical companies are not good at studying how to stop their medicine," Drucker said, "but we need to answer that question." Drucker is among those who sees huge potential for GLP-1s as a way to reduce the dire impacts of obesity — a public health crisis so widespread that just this year, the World Health Organization released its first-ever guidelines to manage obesity starting from childhood.
但他强调，解决长期医疗问题通常需要长期治疗。例如，当你停用用于生发米诺地尔时，脱发就会重新开始。如果你突然停止服用他汀类药物，胆固醇会迅速飙升。GLP-1类药物为什么会有所不同？
But tackling long-term medical issues usually requires long-term treatment, he stressed. When you discontinue minoxidil for hair regrowth, for example, hair loss restarts. If you suddenly stop taking statins, cholesterol spikes fast. Why would GLP-1s be any different?
德鲁克说：“长期用药来控制体重存在很多污名化，但如果患有多发性硬化症、克罗恩病、高血压或高胆固醇，我们绝不会让任何人对此产生疑问。”
"There is a lot of stigma around staying on a medicine to control your body weight for long periods of time, but we would never have anyone question if they had MS or Crohn's or hypertension or high cholesterol," Drucker said.
“我可以列举至少125种需要终身服药来控制的疾病，但出于某种原因，对于GLP-1药物，人们认为，好吧，你应该有能力靠自己做到这一点。”
"I could list at least 125 diseases where you take the medication for the rest of your life to control the disease, but for some reason with the GLP-1 medicine, people think, well, you should be able to do this yourself."
克莱默说，短期使用可能“弊大于利”，并表示确实还没有研究能够表明，通过逐渐减量而不是快速停药，能否维持使用GLP-1的心血管获益。
Short-term use may 'cause more harm than good' Kramer said there really hasn’t been research to help show if the cardiovascular benefits of being on a GLP-1 can be maintained by gradually tapering off rather than quickly stopping.
鉴于从常见的胃部不适到急性胰腺炎，再到罕见的视力丧失报告，可能会出现一系列副作用，该团队还将密切关注各种症状和不良事件。收听：在GLP-1的时代，“瘦”意味着什么？
The team will also be watching for symptoms and adverse events, given there can be a range of side-effects from common stomach upset to acute pancreatitis to rare reports of vision loss. Listen What does thin mean in the age of GLP1s?
收听：为什么更便宜的减肥药对加拿大人来说可能是一个“游戏规则的改变者”在她的团队的研究结果出来之前，对于想要短期使用减肥药的加拿大人，克莱默有什么建议？
Listen Why cheaper weight loss drugs could be a 'gamechanger' for Canadians Kramer's advice for Canadians who want to do a short-term stint on a weight-loss drug before her team’s results come in?
她说：“有些患者想要减掉，比如，三磅的体重，因为‘我两周后要参加婚礼’……这不是这些药物的用途。”
"Patients who want to shed, like, three pounds because, ‘I have a wedding in two weeks’ … that is not what the medications were meant for," she said.
“如果您打算在没有经过适当评估的情况下短期服用某种药物……这可能弊大于利。”
"If you are thinking of taking a medication without the proper assessment over a short term … it may cause more harm than good."