A brand new ‘miracle’ weight-loss drug actually works — elevating large questions

In the summertime of 2018, Lisa Robillard left her physician’s workplace and walked down the lengthy hall of a medical advanced in suburban Virginia. She’d simply had an appointment with one more doctor who might solely advocate “weight loss program and train” when she introduced up her life-long battle along with her weight. Robillard was 11 when she attended her first Weight Watchers assembly along with her household, who celebrated hitting their weight-reduction plan targets by going out for ice cream. Later, when her first fiancé proposed, the ring was conditional on dropping a number of gown sizes. She misplaced the load however, once they cut up, it piled again on. Now, after 40 years of yo-yoing, she was dispirited.

Then Robillard glimpsed an indication hanging on one of many doorways alongside the hall: “Struggling to shed pounds? You don’t must do it alone.” Inside, she discovered a considerably grim clinic of aged vinyl chairs and wall-to-wall beige that didn’t a lot seem like the birthplace of a surprise drug. However she additionally learnt that an increasing number of scientists consider weight problems is a illness relatively than merely ensuing from unhealthy habits and that, for the significantly obese, way of life adjustments won’t ever be solely efficient. Ultimately, she joined a trial the clinic was operating for a brand new drug referred to as Wegovy. “I want I had recognized sooner that it wasn’t only a lack of willpower,” says Robillard, who’s now 55. “The various {dollars} spent on going to weight-loss [meetings], the years of beating myself up, the years of self-hate. I want I had recognized that it wasn’t my fault.”

Wegovy, made by Danish drugmaker Novo Nordisk, is the primary in what’s shaping as much as be a brand new technology of weight problems therapies, which use a hormone to manage urge for food. (The title is the results of a nebulous bureaucratic course of involving pharmaceutical regulators and the corporate’s entrepreneurs.) The typical affected person within the research by which Robillard participated misplaced 15 per cent of their physique weight, about thrice greater than on earlier medicine. Almost a 3rd of them misplaced nearly as a lot as they might after weight-loss surgical procedure. Robillard misplaced 57 kilos. The US Meals and Drug Administration accredited Wegovy for common use in June 2021.

Wegovy arrived in the marketplace amid a worldwide weight problems disaster. Virtually half of People are anticipated to be overweight by 2030, a Harvard research discovered, and that might account for as much as 18 per cent of healthcare spending on associated circumstances, starting from coronary heart illness and stroke to osteoarthritis. Worldwide weight problems charges have tripled since 1975, with 650 million adults overweight in 2016, based on the World Well being Group. In 2019, the OECD declared that developed international locations’ plans to sort out the issue had been largely failing. And the Covid-19 pandemic solely underscored that weight problems places folks at better threat for infectious illness.

Regardless of the huge want, many main pharmaceutical corporations have held again from creating weight-loss medicine, partially as a result of the class is marred by a protracted historical past of quackery and security scares. From the Nineteen Thirties to the Sixties, the business poured cash into slimming capsules primarily based on amphetamines. These finally fell out of favour as a result of they had been extremely addictive and had dangerous negative effects. Within the Nineties, fen-phen — a mixture of fenfluramine and phentermine — turned so well-liked that weight-loss clinics sprung up throughout the US simply to prescribe it, although some sufferers on the drug skilled manic episodes. It was later taken off the market after a research confirmed as much as a 3rd of sufferers might undergo from coronary heart valve defects. As not too long ago as 2020, US regulators compelled the withdrawal of weight-loss drug Belviq due to considerations it elevated the danger of most cancers. For probably the most determined, surgical procedure has develop into well-liked, although it’s costly and comes with its personal dangers and restrictions.

Maybe unsurprisingly, Wegovy — a weekly injection sufferers self-administer utilizing a small machine that appears a bit like an EpiPen — has loads of followers. Sufferers like Robillard, for one. Whereas her day job remains to be working for a union, she now works part-time as a Novo Nordisk spokesperson, giving motivational speeches to employees. Unpaid celeb endorsements embrace enterprise capitalist Marc Andreessen, who says the drug fully modified his relationship with meals, and Elon Musk, who has cited it on Twitter. Novo Nordisk not too long ago greater than doubled its gross sales targets for weight problems medicine to $3.7bn by 2025. Its share worth has risen 26 per cent prior to now yr. However earlier than the corporate could make Wegovy mainstream, it has to persuade medical doctors to prescribe it and insurers and governments to pay for it. It has to influence sufferers to join some heinous negative effects. After which there’s the small matter of overturning centuries of, because it seems inaccurate, assumptions embedded within the Latin root of the phrase weight problems: “having eaten till fats”.

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Because the second half of the twentieth century, the rich have tended to remain skinny, a advantage of accessing medical care, wholesome meals and free time to train. However for many of human historical past, shortage reigned, and the wealthy flaunted their fats. Corporal extra was proof of a bountiful desk and maybe even genes that may shield offspring in occasions of famine.

However the story of weight problems has all the time been sophisticated. The toll it takes was clear to the traditional Greeks, Hippocrates noting that “corpulence is just not solely a illness itself, however the harbinger of others”. Then Christianity got here alongside and yoked urge for food to lethal sins equivalent to gluttony and sloth. In Dante’s inferno, the souls of meals addicts are punished by icy rain, representing the harm their overindulgence does to themselves and others.

Novo Nordisk scientists have considered weight problems as a illness for 25 years. It’s an uncommon pharmaceutical firm. Based mostly simply exterior Copenhagen and nearly a century outdated, it’s managed and part-owned by a charitable basis that invests in scientific analysis, start-ups and humanitarian tasks. The world’s seventeenth largest pharmaceutical firm by income, it generated gross sales of about $20bn final yr.

The corporate’s employees likes to say Novo Nordisk was born from a love story, as a result of its founder sought out insulin for his diabetic spouse, bringing it again to Denmark for her from Canada earlier than constructing his enterprise. So its scientists paid consideration in 1987 when three separate groups of educational researchers — in Copenhagen, Boston and London — concurrently found the impact of a hormone generally known as GLP-1 on insulin. Once we eat, cells within the small gut secrete GLP-1, inflicting the discharge of insulin, which in flip tempers fluctuations in blood sugar ranges.

Again then, scientists thought the hormone held promise serving to diabetics restore regular insulin manufacturing. Whereas experimenting with how one can create a brand new GLP-1-based drug within the Nineties, Novo Nordisk lab scientists seen their mice and rats started to shed pounds. The hormone’s impact on the mind, they found, is to scale back urge for food and create a sense of fullness. That is precisely the way it labored for Robillard in 2018; she felt her thoughts free of its obsession with consuming.

Peter Kurtzhals is speaking to me over Zoom from a convention room on the firm’s Danish headquarters. A senior scientist at Novo Nordisk, he cuts the determine of a no-nonsense researcher however lights up describing why the lecturers who found the hormone must be thought of for a Nobel Prize. He says GLP-1 stands out as the pharmaceutical equal of a Swiss military knife as a result of Novo Nordisk can also be testing medicine primarily based on the hormone to deal with kidney illness, an more and more prevalent liver situation generally known as NASH, even Alzheimer’s. “It’s type of superb, philosophically, that we’ve got a pure hormone that may be pharmacologically utilized in such a wide range of circumstances,” he says.

This pure hormone has a flaw: it’s so unstable that it lasts mere minutes within the physique. In 2005, one San Diego biotech firm marketed a drug primarily based on an analogous hormone produced within the venom of Gila monster lizards as a result of it lasted for a number of hours, relatively than minutes. Novo Nordisk’s scientists laboured for years to create a steady model of GLP-1 that might be used as medicine.

Testing their potential medicine in animals proved troublesome: a dose that saved a pig satiated won’t work in a human, and it proved particularly tough to trace vital negative effects. “It’s arduous to ask the canine or the pig whether or not they really feel nauseated,” Kurtzhals says.

In 2009, Novo Nordisk received approval for its first GLP-1-based remedy, a day by day drug referred to as Saxenda. However the 5 per cent weight reduction it provided sufferers wasn’t sufficient to make it a blockbuster. The corporate’s scientists searched by means of a whole bunch of potential medicine till they stumble on semaglutide, christened with the model title Wegovy when it was accredited within the US final yr.

Wegovy is similar to Saxenda. Each are 90 per cent the identical as naturally occurring GLP-1, however due to its totally different chemical aspect chain, Wegovy will be taken weekly. (The corporate doesn’t know precisely why it proved a lot more practical, however animal research recommend it’s distributed in another way within the mind.) When an early Wegovy trial confirmed the drug’s energy, Kurtzhals says it felt “too good to be true”. Then a late-stage trial confirmed the beautiful weight reduction, and the crew celebrated. “They felt like they’d received an Olympic medal,” he says.

In the meantime there may be one cardinal thriller about weight problems for scientists to unravel. Till they do, sufferers can be on the drug for all times. Consultants more and more agree that the tug of struggle over her weight that Robillard described to her physician in Virginia is a literal factor for many individuals. As soon as it turns into overweight, the human physique tends to push itself to rebound to its earlier highest weight. Scientists don’t totally perceive why, or how one can cease it. Many speculate that our brains haven’t adjusted to dwelling in a time of lots. “There’s been a range bias in the direction of these individuals who might higher shield physique weight throughout occasions of famine,” Kurtzhals says. “However now we don’t have a scarcity of meals.”

When a affected person stops taking Wegovy, their urge for food returns inside weeks and so they pack on weight. Within the research run by Robillard’s physician, Domenica Rubino, the sufferers who got here off the drug regained 7 per cent of their physique weight. “We used to assume that behaviour causes the load state, however now we predict the load state really causes the behaviour,” Rubino says. There could also be even worse negative effects of coming off the drug. Lower than every week after Robillard stopped taking it on the finish of the trial in November 2019, she began having panic assaults. “Each circuit began fascinated with the cravings,” she says. She regained 20 kilos.

Novo Nordisk’s long-term ambition is to remedy weight problems by discovering how one can cease the physique bouncing again. Till then, Kurtzhals believes folks ought to consider treating weight problems as they do different continual illnesses. “For some purpose, many individuals have a better time understanding that your blood strain medicine is for all times than understanding that your remedy of weight problems can also be for all times,” he says. A part of that purpose stands out as the price ticket. In contrast to generic blood strain medicine that now value $10 a month, Wegovy’s month-to-month checklist worth within the US is about $1,350.

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Many sufferers know, intuitively, that weight problems is a illness, and a few had been primed for Wegovy’s US approval. Inside every week, Kimberley Shoaf, a public well being professor on the College of Utah, visited her physician and found she wasn’t the clinic’s first affected person to request Wegovy. Afraid of the surgical procedure that she noticed as the one different, she pushed to get a prescription. Prior to now 11 months, she has misplaced 70 kilos, greater than 20 per cent of her weight, and remains to be shedding half a pound every week. She will be able to stroll for longer, her blood strain has dropped, and he or she hopes to quickly have the phrases “pre-diabetic” erased from her medical information. “Despite turning 60, I really feel youthful,” she says.

These outcomes are the explanation she’s keen to place up with Wegovy’s important negative effects. At first, she threw up each week after taking the injection. Now she suffers constipation. Comparable negative effects had been reported within the trial and on medicine.com, the place sufferers universally reward the ensuing weight reduction however ceaselessly complain of a continuing “morning illness”. The drug additionally comes with a warning it might enhance the danger of thyroid most cancers, although to date that has solely been discovered to be the case in lab animals.

Whereas it’s beginning with well-informed sufferers like Shoaf and Andreessen, Novo Nordisk’s subsequent problem is to transform overweight individuals who by no means search remedy. Which is the place Queen Latifah is available in. The drugmaker is paying the actor to guide an unbranded marketing campaign referred to as “It’s Greater Than Me”. In on-line movies, Latifah performs an emergency room physician lecturing as an obese affected person is wheeled in affected by “stigma”, for instance. She by no means explicitly says the drug’s title. At dwell occasions with consultants in New York, Los Angeles and Houston, Novo Nordisk hopes Latifah succeeded in stirring up demand. A well-known black girl, the corporate hopes, will attraction to the 4 out of 5 African American females who’re overweight.

Once we communicate over video name, Latifah, who wears a darkish blue wrap gown, is poised. “It’s not nearly picture,” she says. “It’s about science. It’s about genetics. It’s about hormones.” She says she didn’t even perceive that she had a weight downside till she requested a private coach to assist her drop 25 kilos for her function within the 2003 comedy Bringing Down the Home. Latifah describes having her measurements taken: “She actually walked me by means of my butt. She was like, ‘You might be overweight.’ I had by no means heard that time period apply to me,” the actor says. “So then we began a plan, and it labored.”

After I ask what the plan was, she says weight loss program and train, including “I’ve by no means actually been one for the medical . . . the drugs aspect of this.” She stops herself, maybe realising this won’t go down nicely with the PR reps sitting silently on the decision. “Properly, let me simply put it this fashion . . . I noticed folks go loopy on a fen-phen bender like I’ve by no means seen in my life.” Latifah might have inadvertently hit on Wegovy’s greatest impediment: the deeply entrenched stigma round treating weight issues medically.

This problem falls, partially, to Vince Lamanna, Novo Nordisk’s newly appointed US gross sales chief and a strolling commercial for Wegovy. His smooth gray and blue verify go well with appears to be like like it will not have match him earlier than he misplaced 30 kilos, 15 per cent of his physique weight, on the drug. Enjoying with the empty injection pen that he carries to indicate how simple Wegovy is to self-administer, he says it’s “actually robust” to promote. “We’re nonetheless the one firm doing it, doing it alone,” he continues.

Doug Langa, an govt vice-president at Novo, has spent 30 years promoting medicine for nearly each illness. But he has by no means encountered a job like this: a illness for which just one in 10 People search remedy. And once they do, they battle to seek out a health care provider who will pay attention. “That is far and away probably the most difficult, with out query,” he says.

Novo Nordisk put “toes on the road” inside 72 hours of Wegovy’s approval, sending what it calls “educators” into medical doctors’ workplaces across the US. Lamanna anticipates it might take two to 3 years to alter the minds of major care physicians. Endocrinologists and weight administration specialists have a tendency to grasp that weight-reduction plan can’t all the time compete with the physique’s drive to bounce again to a heavier weight. Virtually 10 years have handed because the American Medical Affiliation first declared weight problems a illness, but the typical physician barely spent any time studying about it at medical college. “The most important false impression is that it’s energy in and energy out. So, how a lot you train and the way a lot you eat,” Lamanna explains. Rubino, the physician who ran the Wegovy trial in Virginia, provides that major care medical doctors hardly ever perceive the roles performed by diet and hormonal regulation, and that that vacuum is crammed with society’s stigma towards overweight folks.

Whereas sending gross sales representatives to medical doctors is regular apply in American medication, endeavor a whole re-education is harking back to how opioid makers tried to reclass ache as a “fifth important signal” in order that clinicians felt they needed to deal with it with a drug. Rubino, who was paid by Novo Nordisk to run the trial, accepts folks may assume the corporate’s schooling programme is self-serving. “However, to date, I feel individuals are making an attempt to be very cautious about their function,” she says.

Lamanna’s crew is unlikely to remain alone in its mission to unfold the phrase. Novo Nordisk’s longtime rival in diabetes remedy, Eli Lilly, not too long ago printed what seem like even higher topline outcomes for its weight problems drug, ​​Tirzepatide. Almost two-thirds of contributors trialling its GLP-1-based remedy misplaced 20 per cent of their physique weight. Pfizer, too, is engaged on a remedy primarily based on the hormone. AstraZeneca and its associate Regeneron, in addition to start-ups Versanis and Gelesis are taking totally different scientific approaches to the identical downside. All of them are hoping to interrupt into — and broaden — the marketplace for weight problems medicines, equivalent to Wegovy. In the event that they succeed, there can be much more pharmaceutical preachers to transform the hundreds of thousands to medical remedy.

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Even when Novo Nordisk can win medical doctors over, it faces a better problem to persuade reluctant payers. Some 80 million overweight People don’t have insurers who can pay for Wegovy. Whereas it’s on most insurers’ lists of formally coated medicine, it’s usually in a life-style class, alongside therapies for points equivalent to erectile dysfunction. Payers additionally put up hurdles so sufferers should receive permission earlier than filling a prescription. One Maryland pharmacist informed me she had seen many prescriptions for Wegovy, none of which had ever come again after being despatched for authorisation.

Rubino says she turns into exasperated ploughing by means of attraction kinds for sufferers who she believes must be exceptions, equivalent to one whose bipolar medicine induced weight acquire. She says she as soon as spent two hours on the telephone making an attempt to get the proper case ID and fax quantity to ship alongside one attraction. Often, appeals are ignored or rejected with out purpose, she provides.

“It’s a system that’s been put in place to mainly stop you from being persistent. And I’ll do it for my sufferers. Nevertheless it takes an amazing period of time,” she says. Rubino believes insurance coverage corporations additionally stigmatise weight problems. “For the longest time, the reason of why it wasn’t coated was there wasn’t enough weight reduction,” she says. “Now, I don’t know what the excuse is.”

Main US insurers Aetna, UnitedHealthcare and Cigna didn’t reply to requests for touch upon protection choices. James Gelfand, who leads public affairs on the Erisa Business Committee, which represents US employers that sponsor well being plans, says earlier weight problems medicine had been so ineffective it was a “no brainer” to refuse protection. At present about half of all US employers have opted to place Wegovy on their checklist of coated medicine. However they could nonetheless limit it to sure teams of sufferers or make those that qualify leap over different hurdles.

Wegovy is perhaps totally different, however he suspects employers will wait to gather extra knowledge after which, maybe, start with these most in want. If drugmakers actually need it coated, Gelfand suggests they might minimize costs. “Drug corporations do a fragile dance making an attempt to extract as a lot cash as they presumably can from third-party payers, realizing a person affected person won’t ever have means to have the ability to afford the drug,” he says.

Novo Nordisk additionally has to win over Congress to get Medicare, the US’s publicly funded medical health insurance for seniors, to cowl weight problems medicine. For 10 years, legislators have proposed eradicating the ban that stops Medicare from paying for weight problems therapies, however it’s not clear if the political will to take action exists. The Danish drugmaker may notably battle to win politicians’ votes after insulin, considered one of its greatest merchandise, turned the “poster baby” for rising drug costs, based on Novo Nordisk’s Langa.

A congressional committee accused the corporate this yr of jacking up the value of insulin 28 occasions since 2001, leading to a 628 per cent worth enhance. Novo Nordisk argues that its web worth has really fallen and that the will increase are going to middlemen and insurers. Langa half-jokes that if you wish to see him actually harassed, watch a video of him testifying in Congress.

The prospect of dropping protection after the age of 65 worries sufferers who know the load might pile proper again on. Gwendolyn, a 66-year-old musician, misplaced 80 kilos in Eli Lilly’s drug trial. She says she was a “strolling coronary heart assault”, whose issues had been exacerbated when she developed lengthy Covid. Now she appears like she might work for a lot of extra years. But when Medicare received’t pay, she’ll have to seek out the cash or would even think about biking on and off the drug to avoid wasting prices.

Eli Lilly has not but introduced the value of its weight problems drug, although it can most likely be in the identical ballpark as Wegovy. Gwendolyn describes it as “very scary” that the drugs might value a lot, although she has some sympathy that drugmakers need their a reimbursement from trials that value a “fortune”. “However if you realise the sheer numbers of individuals that may take this, I might assume that they might earn cash by scale,” she says. “I really feel like what that is going to be is extra like a designer drug that rich folks will take to assist scale back their weight . . . that’s type of unhappy.”

Within the UK, the NHS has a vested curiosity in tackling weight problems, saving on future related medical prices. About 28 per cent of adults in England had been overweight in 2019, nearly double the speed in 1993 and one of many worst in Europe. In February, the UK’s Nationwide Institute for Well being and Care Excellence issued preliminary steerage advising that Wegovy will be given to probably the most obese sufferers, with a minimum of one obesity-related situation, alongside a weight loss program and train plan, however just for two years.

Manufacturing-related provide issues imply it’s not but accessible. When it’s, UK sufferers will get it for the prescription value of £9.35 per merchandise. When there are extra doses accessible, Novo Nordisk will broaden promotion throughout Europe, the place some well being authorities together with these in Eire, the Netherlands and Switzerland already cowl the price of Saxenda.

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Even when Novo Nordisk and its rivals achieve getting their drug accepted by the individuals who maintain the purse strings, they’ll nonetheless face opponents who reject the entire premise that weight problems must be handled with medication. Advocates of “physique positivity” and a few weight administration consultants consider well being metrics equivalent to blood strain or blood sugar are much more helpful than physique mass index. The corporate is hoping to sway doubters with a trial, which experiences later this yr, that can present whether or not Wegovy reduces the danger of cardiac issues.

Marquisele Mercedes, a doctoral scholar in public well being at Brown College, is fed up listening to that Wegovy is a “miracle”. She warns the drug might really encourage “weight biking”, which is “extremely harmful”. Research present that dropping and regaining weight might enhance the danger of circumstances equivalent to diabetes. “All the issues we attribute to fatness, like cardiovascular threat, diabetes, melancholy, nervousness . . . have really been discovered to be associated to weight biking,” she explains.

Some critics concern that Novo Nordisk can be too profitable in changing medical doctors. Clinicians usually discover medicine — equivalent to overprescribed antidepressants — are a handy crutch once they lack the time or ability to dig into the advanced roots of an issue. Krista Varady, a professor of diet on the College of Illinois, recounts her “eye-opening” expertise at a convention of diabetes specialists who’ve used GLP-1 for years. Some mentioned they instantly put 95 per cent of sufferers on the drug, with out ready to see if weight loss program or train would work. “I used to be shocked,” she says. “However our system is designed to deal with the sick, to not do prevention.”

Varady worries that it will likely be simpler to medicate a world that she describes as “obesogenic” — tending to trigger weight problems. Wegovy might develop into a societal sticking plaster, permitting meals corporations to proceed promoting junk and pharma corporations to revenue from slimming folks down. She believes it will be extra “humane” if governments discovered methods “to show folks or tax them”, such because the UK levy on sugary drinks.

Mercedes believes Novo Nordisk’s efforts to counter stigma — the Queen Latifah marketing campaign — might really find yourself embedding current bias. “They’re promoting you an answer to the discrimination and stigma you face by supplying you with a approach to be smaller,” she says. It’s “actually simply promoting. We’re transitioning from the non-public failure, missing willpower, missing self-control narrative, to this narrative that claims ‘Weight problems is a illness, you want a prescribed remedy’ . . . so we are able to promote weight-loss medicine,” she says. “They’ll make a killing.”

Novo Nordisk doesn’t consider there’s a binary selection between providing medicine and altering society. Propelled by the potential for large earnings, it could be extra profitable than the patchy and poorly funded efforts to deal with the underlying circumstances that exacerbate weight problems, together with psychological well being, poverty and lack of entry to contemporary meals. The corporate’s scientists are engaged on improved variations of Wegovy — together with a capsule — and mixtures they hope might assist folks lose much more weight.

Lisa Robillard feels she is likely one of the fortunate ones. Her insurance coverage covers Wegovy, so it solely prices her $40 a month. When the drug was accredited, she needed to go to 4 or 5 pharmacies to seek out it, however now has a dependable provide. Her knees and ankles don’t harm, she’s stopped loud night breathing, and he or she has extra vitality. She says she has no downside taking the drug ceaselessly. But she resents individuals who assume it’s a fast repair. She says she has to proceed watching what she eats and exercising. “It’s not such as you take the drug, after which you may eat pie and cookies all day.”

Hannah Kuchler is the FT’s international prescription drugs correspondent

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