Every day seems to bring more exciting news. First the drugs tackled diabetes. Then, with just an injection a week, they took on obesity. Now they are being found to treat cardiovascular and kidney disease, and are being tested for Alzheimer’s and addiction. It is early days yet, but glp-1 receptor agonists have all the makings of one of the most successful classes of drugs in history. As they become cheaper and easier to use, they promise to dramatically improve the lives of more than a billion people—with profound consequences for industry, the economy and society.

似乎每天都有更多振奮人心的消息。這些藥物最初用于治療糖尿病，后來發(fā)現(xiàn)每周只需注射一次可以減肥，現(xiàn)在發(fā)現(xiàn)可以治療心血管和腎臟疾病，并且正在進(jìn)行旨在治療阿爾茨海默病和成癮的試驗(yàn)。雖然只是初期階段，但GLP-1受體激動劑堪稱有史以來最成功的一類藥物。隨著價格越來越便宜和更易使用，它們有望顯著改善數(shù)十億人的生活，對工業(yè)、經(jīng)濟(jì)、社會產(chǎn)生深遠(yuǎn)的影響。
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In the three years since semaglutide was approved for treating obesity, it has taken America by storm. After decades of disappointing “miracle cures”, these drugs work. Image-conscious influencers and well-heeled financiers are not their only users. Already one in eight American adults has been on glp-1 drugs. Novo Nordisk, maker of semaglutide, branded Ozempic for diabetes and Wegovy for weight loss, and Eli Lilly, which makes tirzepatide, a more effective alternative, have together added around $1trn in market value since 2021.

自從三年前司美格魯肽獲準(zhǔn)用于治療肥胖癥以來，這種藥物迅速風(fēng)靡美國。在“神奇療法”令人失望數(shù)十年后，這些藥物見效了。注重形象的網(wǎng)紅和闊綽的金融家并不是唯一的用戶，目前已有八分之一的美國成年人在使用GLP-1藥物。司美格魯肽由諾和諾德公司生產(chǎn)，用于治療糖尿病和減肥的品牌名分別為諾和泰（Ozempic）、諾和盈（Wegovy）。替爾泊肽由禮來公司生產(chǎn)，具有更顯著的功效。自2021年以來，兩家公司的市值總共增加了約1萬億美元。

The action is now moving beyond America. With over two-fifths of the world overweight or obese, demand for glp-1 drugs is voracious. Pharma companies are racing to make them work as pills, which would be cheaper to produce than jabs, and to reduce their side-effects. Generic versions for older glp-1 agonists are entering the market. Semaglutide is to come off patent in Brazil, China and India in 2026; eight such drugs are in the works in China. That is just as well. As incomes in the developing world have risen and life has become more sedentary, people’s waistlines are catching up with those in the West.

這一趨勢正在向美國以外的地區(qū)蔓延。全球有超過五分之二的人超重或肥胖，GLP-1藥物的市場需求是巨大的。制藥企業(yè)正在爭相將其制成片劑，使生產(chǎn)成本低于注射液，并減少副作用。非專利的舊版GLP-1受體激動劑正在進(jìn)入市場。司美格魯肽在巴西、中國、印度的專利將于2026年到期；中國正在研發(fā)八種此類藥物。這樣也好，隨著發(fā)展中國家收入的提高，生活方式日益趨向久坐不動，人們的腰圍正在接近西方人的水平。

Curbing obesity would be consequential. Yet glp-1 drugs promise to do much more. Overweight patients on semaglutide have been found to suffer fewer heart attacks and strokes; the benefits, astonishingly, seem to be largely independent of how much weight is lost. Tirzepatide improves sleep apnoea. Trials show that glp-1 agonists reduce chronic kidney disease in diabetics; and there are signs they may lessen brain shrinkage and cognitive decline in Alzheimer’s. Studies of health records suggest that they may help with addictions, too; people already on glp-1 drugs in America were less likely to overdose on opioids or abuse cannabis or alcohol. Researchers are even talking, in hushed tones, of their anti-ageing effects.

減肥具有重要意義，但GLP-1藥物可能還有其他功效。研究表明，使用司美格魯肽的超重患者在心臟病發(fā)作和中風(fēng)方面的風(fēng)險(xiǎn)顯著降低。令人驚訝的是，這些益處似乎與減肥沒什么關(guān)系。替爾泊肽可以改善睡眠呼吸暫停。試驗(yàn)證明，GLP-1受體激動劑能夠降低糖尿病患者的慢性腎病發(fā)生率；有跡象表明，這種藥物可能減輕阿爾茨海默氏癥患者的大腦萎縮和認(rèn)知能力下降。醫(yī)療記錄研究顯示，它們還可能有助于戒除成癮。在美國，使用GLP-1藥物的患者不容易過量服用阿片類藥物、濫用大麻、酗酒。研究人員甚至私下議論抗衰老功效。

How can one class of drug do so much? As our briefing explains this week, not only do the drugs act in the gut, but they also bind to receptors all over the body and in the brain. The drugs appear to reduce inflammation and interact with mechanisms lixed to cravings and feelings of reward. With every new finding, researchers are learning more about the workings of disease and the lixs between the body and the brain.

一種藥物為何有這么多功效？正如我們本周的簡報(bào)欄目所闡述的，這些藥物不僅在腸道中發(fā)揮作用，而且與全身和大腦中的受體相結(jié)合。這種藥物似乎能減少炎癥，并與欲望和獎賞效應(yīng)相關(guān)的機(jī)制相互作用。每有一項(xiàng)新發(fā)現(xiàn)，研究人員就能進(jìn)一步了解疾病機(jī)制以及人體與大腦之間的關(guān)聯(lián)。

Naturally, more work is needed. Although glp-1 agonists have been used in diabetes for 20 years, some of the newer findings are based on observational studies, and will need to be supplemented by randomised trials. Patients may need to remain on these medicines for their whole lives, and their long-term benefits have yet to be quantified.

當(dāng)然，有必要進(jìn)行更多的研究。雖然GLP-1受體激動劑用于治療糖尿病已有20年，但有些新發(fā)現(xiàn)是基于觀察性研究，需要隨機(jī)試驗(yàn)作為補(bǔ)充?；颊呖赡苄枰K生服用這些藥物，長期功效有待于量化。

That makes the costs uncertain, too. For now the drugs are expensive: tirzepatide is priced at over $500 a month in America. Their immediate side-effects, which can include nausea, pancreatitis, diarrhoea and muscle loss, may be off-putting; the effects from decades of taking them are uncertain. Some worry about the medicalisation of everyday life, and whether people will binge, knowing they can fall back on a cure.

這也使得治療費(fèi)變得不確定。目前這種藥物價格昂貴：在美國服用替爾泊肽的每月費(fèi)用超過500美元。即刻發(fā)生的副作用可能令人反感，包括惡心、胰腺炎、腹瀉、肌肉流失。服藥數(shù)十年的影響尚不明確。有人擔(dān)心日常生活變得醫(yī)療化，人們是否會因?yàn)橹揽梢砸揽克幬锒╋嫳┦场?/b>

Yet with time, experimentation and innovation, the benefits will become clearer, and the costs will come down. Healthy habits and good public-health advice will still matter. But practitioners have long despaired that nothing works for many obese people. If the drugs live up to their early promise, it would be perverse and cruel to deprive patients of medicines that could dramatically improve their lives. The drugs could hold the same promise for addiction.

但隨著時間的推移和更多的試驗(yàn)和創(chuàng)新，益處將變得明朗，費(fèi)用也會下降。健康的生活習(xí)慣和良好的公共衛(wèi)生建議仍然很重要。但醫(yī)生一直對無法醫(yī)治許多肥胖者而感到絕望。如果這些藥物能達(dá)到預(yù)期療效，那么拒絕患者使用可以極大提高生活質(zhì)量的藥物是殘忍和沒有道理的。這些藥物對成癮可能也有療效。

Stand back and the possibilities are thrilling. In 2019 heart disease, stroke, diabetes, Alzheimer’s and kidney disease ranked among the top ten global causes of death. By 2050, as the world ages and developing countries’ health care improves, these diseases will take a bigger toll. Last year more than 100,000 Americans were killed by opioid overdoses and 180,000 died from drink.

重新審視一下，這些藥物的潛力振奮人心。2019年，心臟病、中風(fēng)、糖尿病、阿爾茨海默病、腎病位列全球十大死因。到2050年，隨著世界老齡化和發(fā)展中國家醫(yī)療條件的改善，這些疾病將導(dǎo)致更多人死亡。去年，超過10萬名美國人因過量服用阿片類藥物而死亡，18萬人因酗酒而死亡。

For patients, the new uses of glp-1 drugs would mean not just longer, healthier and more productive lives, but happier ones, too. In a world of abundance people succumb to their impulses even if they know their behaviour is harmful in the long term. Although glp-1 agonists may limit the pleasure of instant gratification, they promise to end intrusive cravings and improve long-term health.

對于患者來說，GLP-1藥物的新用途不僅意味著更長壽、更健康、更充實(shí)的生活，也意味著更幸福的生活。在一個物質(zhì)充裕的時代，即使人們知道自己的行為從長遠(yuǎn)角度有害健康，他們還是會屈從內(nèi)心的沖動。雖然GLP-1受體激動劑可能限制人們及時行樂，但它們有望消除令人煩惱的欲望，改善長期健康。

The total bill for prescribing these drugs could be vast. Yet for governments they would lower some other costs: the direct medical bill for obesity alone amounts to $260bn a year in America; substance abuse is a huge burden for the criminal-justice system. The state would raise less revenue from taxes on alcohol, but income-tax revenues would go up, as the workforce became healthier.

開這些藥物的總費(fèi)用可能很大，但能為政府減少其他開支：在美國，光是肥胖癥的直接醫(yī)療費(fèi)用每年就高達(dá)2600億美元；藥物濫用給刑事司法系統(tǒng)造成了沉重負(fù)擔(dān)。政府的酒稅收入將會減少，但隨著勞動力變得更加健康，所得稅收入將會增加。

Less is moreish

越少越好

Rather as the contraceptive pill encouraged women to stay in education and work, so glp-1 drugs could lead to profound economic and social change by enhancing productivity and freedom. Some business models could be upended. If craving can be controlled, junk-food companies, advertisers and even drug-dealers may shift their focus from quantity to quality.

正如避孕藥激勵女性繼續(xù)接受教育和工作，GLP-1藥物可能通過提升生產(chǎn)力和自由而引發(fā)深刻的經(jīng)濟(jì)和社會變革。一些商業(yè)模式可能被顛覆，如果欲望可以被控制，那么垃圾食品企業(yè)、廣告商、甚至毒販可能注重質(zhì)量，而不是數(shù)量。

Social mores could evolve. In the West thinness is prized as the ideal of beauty, because for so many it is hard-won, whereas obese people suffer discrimination and lower wages. If being thin is easier, that may change. Obesity and addiction may less often be seen as moral failings, but as illnesses that can be treated. The glp-1 revolution is just beginning. Its promise is tantalising.

社會習(xí)俗可能逐漸發(fā)生變化。西方國家以瘦為美，因?yàn)樵S多人不易實(shí)現(xiàn)這個目標(biāo)，而肥胖者則遭受歧視，工資也較低。如果輕松就能變瘦，情況就可能發(fā)生改變。肥胖和成癮可能不再被經(jīng)常視為道德淪喪，而是可以治療的疾病。GLP-1革命才剛剛開始，前景誘人。