How Ozempic, Wegovy maker Novo Nordisk hooked us on weight-loss drugs

Weight problems, by and huge, will not be an issue within the land of the Little Mermaid and midcentury trendy design. In Denmark’s capital, Copenhagen, bicycles outnumber automobiles 5 to 1, folks swim laps in Nyhavn Harbor effectively into September, and—regardless of a transparent fondness for pastries, scorching canine, and alcoholic drinks—apparently few folks placed on weight. The nation has one of many lowest weight problems charges in Europe, although at 18.4% in 2021, it has risen significantly from 6.1% in 1987. 

The remainder of the world, too, is wrestling with rising weight problems. In the USA, 42% of adults are thought of overweight, and practically three-quarters qualify as overweight or chubby. The World Weight problems Federation predicts that 51% of the worldwide inhabitants will likely be chubby or overweight by 2035. 

The answer to this epidemic could very effectively sit a 45-minute bike experience from downtown Copenhagen, on the company workplaces of the Danish pharmaceutical firm Novo Nordisk—now recognized to the world because the maker of Ozempic and Wegovy.  

A lightweight-filled cylinder designed by Henning Larsen, Novo Nordisk’s headquarters pays architectural tribute to the spiral coil of the insulin molecule—the corporate’s conventional income. At the moment, a greater form can be the sickle-shaped molecule of a peptide known as semaglutide, which is utilized in a sort of drug generally known as a GLP-1 agonist. These drugs assist regulate blood sugar in folks with kind 2 diabetes and, by suppressing urge for food, assist customers shed a median 15% of their physique weight over 64 weeks, an quantity similar to gastric-bypass surgical procedure.

At the moment, Novo sells semaglutide in three types: as Ozempic, a once-weekly injectable for treating kind 2 diabetes, and prescribed off-label for weight reduction; Wegovy, a higher-dose injectable accredited for weight reduction; and Rybelsus, an oral kind 2 diabetes drug. (The corporate expects to finish trials of an oral model of Wegovy by the center of subsequent yr.) Miraculous, controversial, and costly, the medication have ignited debates worldwide about all the pieces from entry and pricing to physique picture and the character of weight problems—and unleashed a frenzy.

“Had we predicted this, we might have ready otherwise,” says Novo Nordisk CEO Lars Fruergaard Jørgensen, with typical Danish understatement. Lower than one yr after hitting the market in Denmark, greater than 1% of the inhabitants was taking it, most paying about $340 a month. However Denmark has a inhabitants of simply 6 million. It’s the U.S. math that issues. Right here, the place Wegovy prices about $1,300 a month and Ozempic $1,000, about 1.7% of American adults who noticed a physician final yr had been prescribed considered one of Novo Nordisk’s semaglutide medication.

Pushed by the U.S., Wegovy gross sales hit $1.38 billion within the third quarter of 2023, up greater than eightfold from a yr in the past, and Ozempic gross sales rose about 59% to just about $9.4 billion. Collectively, the medication accounted for greater than half of Novo’s income. The corporate is now forecasting that 2023 income may attain as excessive as $33 billion, a 39% enhance from 2022. In August, the drugmaker overtook luxurious items conglomerate LVMH as Europe’s Most worthy listed firm. At $430 billion, its market capitalization exceeds Denmark’s whole gross home product. “This new era of GLP-1 merchandise have considerably added to market progress,” says Jørgensen, “but additionally grown a extra aggressive market share” for the corporate. Utilizing its weight-loss winnings, Novo is now advancing new makes use of for GLP-1 medication—together with for coronary heart circumstances and power kidney illness—that could possibly be much more profitable. 

Hype across the drugs—and the slimmed-down society that they may usher in—is radiating throughout the financial system. In October, Walmart warned that GLP-1 drugs had been inflicting buyers to pare again on groceries. This revelation created a ripple effect, deflating shares of meals giants like Krispy Kreme, Nestlé, and Mondelez Worldwide. Morgan Stanley has estimated that 7% of the U.S. inhabitants, or 24 million folks, will likely be taking hunger-suppressing weight-loss medication by 2035 and slicing their day by day calorie consumption by as a lot as 30%. Different analysts are anticipating that lighter passengers may save airways vital cash on gas prices.

The medication are sometimes known as runaway successes. And they’re, a lot in order that Novo Nordisk has had hassle maintaining with demand, leaving some sufferers with diabetes—Ozempic’s conventional base—scrambling. However behind the scenes, Novo has spent greater than 15 years creating these shockingly efficient medication, and at the least a half dozen years engineering their extensively profitable public rollout, particularly within the U.S.

At house in Denmark, the place the corporate employs some 21,000 folks, Novo Nordisk has a popularity as an enlightened company. By its basis, it distributed grants price about $1 billion to scientific and cultural initiatives in 2022 alone. That largesse at house is made doable by its laser-focused business strategy, which hinges on tapping into the self-importance of People and discovering the fats within the profitable U.S. healthcare system.  

When Jimmy Kimmel hosted the 2023 Academy Awards in March, he opened with a zinger: “After I go searching at this room I can’t assist however surprise, ‘Is Ozempic proper for me?’”

The joke, aimed on the ranks of out of the blue svelte stars within the room, was a nod to Novo’s more and more ubiquitous adverts. Since Ozempic’s launch as a sort 2 diabetes drug within the U.S. in early 2018, the corporate has spent lots of of thousands and thousands of {dollars} on direct-to-consumer advertising and marketing, together with TV adverts. In 2022, it put $180 million towards Ozempic adverts, together with an estimated $157 million on TV spots within the U.S., in accordance with advert measurement agency iSpot.television. (The U.S. and New Zealand are the one nations that enable direct-to-consumer prescription drug promoting.) Novo spent one other $120 million on adverts for Ozempic within the first six months of this yr, and $20 million to advertise Wegovy, in accordance with analytics agency MediaRadar.

By spring 2023, it was unattainable to keep away from the earworm jingle of the “Oh, oh, oh, Ozempic” ads (set to the Nineteen Seventies pop music “Magic” by Pilot). These commercials not solely famous the drug’s advantages for blood glucose and cardiovascular considerations, additionally they pointedly talked the common 12 kilos that sufferers misplaced in scientific trials. Among the many elite crowd in Los Angeles’s Dolby Theater, it was already widespread data that Ozempic wasn’t only for diabetes.

It wasn’t simply Hollywood driving demand for the thin shot. By late 2022, the time period “Ozempic” had greater than 300 million views on TikTok. Everybody from suburban mothers to Elon Musk was hopping on social media to share their (largely) optimistic experiences with GLP-1 agonists. Adverts for on-line pharmacies providing semaglutide proliferated on city subways, and med spas touted their entry to Ozempic, overtly flouting restrictions on advertising and marketing off-label makes use of of medicines. Insurance coverage corporations scrambled to replace their protection. And Novo Nordisk, going through provide chain points, struggled to maintain up with the demand that it had created. 

It was a state of affairs unattainable to think about when Novo Nordisk was created, in 1989, with the merger of the Danish pharma corporations Nordisk Insulinlaboratorium and Novo Therapeutisk Laboratorium, which because the Nineteen Twenties had produced medicines primarily based on insulin, a peptide hormone that regulates blood sugar ranges. At the moment, the corporate sells roughly half of all insulin globally, by worth, a enterprise that introduced in about $7.6 billion in 2022.

By January 2017, although, when Jørgensen took over as CEO, the corporate’s insulin enterprise had plateaued. “We had a scenario the place progress was low,” he remembers. The U.S. has historically accounted for practically half of the insulin market, however competitors and more and more giant reductions negotiated with state Medicaid applications and pharmacy distributors had been driving down costs. Fortunately, Jørgensen had a brand new class of medication to rally the corporate round: GLP-1 agonists, which mimic the motion of a intestine hormone known as glucagon-like peptide 1 to stabilize blood sugar.

“You may say we’ve got been on the GLP-1 marketplace for some 15 years,” he says. Novo first began analysis into GLP-1 medication to deal with kind 2 diabetes within the early Eighties. However the work languished till Novo scientist Lotte Bjerre Knudsen created an analog of GLP-1 known as liraglutide. Marketed as a once-daily injectable known as Victoza, liraglutide was accredited by the FDA in 2010 for diabetes, and in 2014, as a weight-loss drug known as Saxenda. 

Most sufferers taking Victoza misplaced lower than 10% of their physique weight. “That was one of the best that was round,” says Jørgensen. “However it nonetheless wasn’t one thing that was extensively used.” Novo’s subsequent molecule—semaglutide—crossed a threshold, bettering diabetes management and inflicting a median weight lack of 15%. That “was a sport changer,” he says.

Novo began reporting scientific information from trials of semaglutide—together with its weight-loss “facet impact”—in late 2016. By the point the FDA accredited Ozempic in December 2017 to be used for kind 2 diabetes, “sufferers had been mobilized,” Jørgensen says. “For the primary time, we had a product the place sufferers went to the doctor to ask for the medication, and [then] the doctor requested us about it.”  

Sufferers could have been in search of out Novo’s medication, however the firm was serving to them alongside, particularly in North America, a territory liable for practically half of its revenues final yr. With a inhabitants of practically $340 million folks and the very best drug costs on the earth, the U.S. is a proverbial money cow for drugmakers. And for a corporation promoting medication for diabetes and weight problems, the U.S. actually delivers, with a excessive prevalence of each. The Federal Commerce Fee estimates that U.S. customers spend $33 billion per yr attempting to both drop pounds or stop weight acquire.

Capturing this market was a yearslong effort. Doug Langa, Novo’s head of North America operations, says that his division underwent a profound transformation in 2017, as Ozempic was nearing FDA approval. “We had been like a Components One racing automotive in a pit cease,” he remembers. “We had been going to take off our insulin tires and placed on our GLP-1 tires, which meant taking lots of representatives and advertising and marketing spend and transferring it into GLP-1.”

“We knew that we had one thing particular with Ozempic,“ remembers Dave Moore, Novo’s government vp of company growth, who presided over the North America launch. “The numerous scientific trials, tens of 1000’s of sufferers, had been exhibiting this was a novel alternative. Lengthy-term, Ozempic was so vital for the group as a result of we knew that ongoing R&D was going to result in different alternatives and different sufferers.”

Moore says that, on the time, it was a problem to get docs “to consider weight problems as a severe power illness” and as a gateway to different issues and circumstances. Educating medical professionals had lengthy been a spotlight within the advertising and marketing of the corporate’s diabetes merchandise, “so it was a pure changeover for weight problems as effectively,” he says.

Novo’s “training” finances has been beneficiant. Between 2013 and 2022, in accordance with a current Reuters investigation, Novo spent at the least $25.8 million on U.S. docs, associated simply to its weight-loss medication, Wegovy and Saxenda. That features talking and consulting charges, meals and beverage prices, and journey and lodging bills. In accordance with data from the Facilities for Medicare and Medicaid Companies, in 2022 alone, Novo spent $11 million on meals and journey for U.S. docs to advertise its GLP-1 medication, shopping for some 457,000 meals and funding journeys to London, Paris, Orlando, and Honolulu. By comparability, Eli Lilly spent roughly $3.5 million in 2021 on meals and journey to advertise its GLP-1 medication, Mounjaro and Trulicity.

Wining and eating docs is mostly authorized, though conversations between pharma gross sales reps and docs are ruled by a code of ethics that limits, amongst different issues, sharing details about future or off-label indications—resembling, say, utilizing Ozempic for weight reduction. However cash and meals make a distinction, even when docs want to attach the dots themselves. An analysis by ProPublica from 2016 discovered that docs who acquired trade funds, and even only a meal, prescribed higher-priced brand-name medication at a a lot increased price than their friends, versus cheaper generics.

Novo Nordisk has skirted moral strains previously. In 2017, the corporate settled a Division of Justice probe right into a “white coat advertising and marketing scheme” that allegedly included paybacks to docs and disguising salespeople as medical educators within the promotion of three diabetes medication. In June 2011, the corporate paid $25 million to settle a lawsuit over alleged improper promotion of an anti-clotting medication for off-label indications. It additionally reached a $1.725 million cope with the U.S. Lawyer in Brooklyn addressing allegations that gross sales reps in a number of states paid pharmacists to advocate two of its diabetes therapies. (Novo Nordisk didn’t admit wrongdoing in both settlement.) This January, the Physicians Committee, a nonprofit public well being advocacy group, filed a complaint with the FDA arguing {that a} 13-minute 60 Minutes story about Wegovy was so one-sided—and Novo Nordisk such a giant advertiser—that the “information” spot amounted to an advert, violating the FDA’s requirement that adverts disclose drug dangers.

There’s additionally the numerous challenge of off-label prescribing. Novo has adopted the regulation in not advertising and marketing Ozempic solely for weight reduction. However off-label prescriptions have each fueled the corporate’s rocket-ship income progress and led to shortages for diabetes sufferers. (Wegovy is accredited for weight reduction, however manufacturing of the drug gained’t catch as much as demand for a lot of months.) Knowledge on prescribing developments in 50 main U.S. cities, analyzed by Trilliant Health for CNN, reveals off-label prescribing of Ozempic hovering nationwide. In some cities—together with Boston and Hartford, Connecticut—about half of Ozempic prescriptions within the first quarter of 2023 went to individuals who didn’t have a historical past of diabetes.

“Don’t get me began on Ozempic,” says an ob-gyn within the San Francisco Bay Space. “Our sufferers are provided it in the event that they meet a couple of scientific standards for weight reduction, and you may manipulate the system so that you [qualify for insurance] with little or no copay.”

There’s nothing unlawful or unethical about a physician prescribing an accredited remedy for one thing exterior its indicated use, if it’s for a great medical cause. However Ozempic prescribing has been pushing the bounds. “There are many folks which can be utilizing this like a fad weight-reduction plan,” says Scott Kahan, an weight problems medication specialist on the Nationwide Heart for Weight and Wellness in Washington, D.C. “They’re shedding 40 kilos in two, three months, they usually’re making themselves sick.” 

The unwanted effects of semaglutide can embody delicate to extreme intestinal issues, resembling nausea, constipation, and diarrhea. Too-rapid weight reduction can result in decreased muscle mass and “Ozempic face”—sagging and growing old pores and skin. There are additionally extra alarming tales. At the very least 265 studies have been filed with the FDA since 2010 describing suicidal ideation or habits in sufferers taking GLP-1 medication, in accordance with a Reuters report; the European Medicines Company is evaluating about 150 studies of doable instances of self-injury and suicidal ideas, in accordance with a July assertion. “There are issues that have to occur to make the remedy work effectively,” Kahan says, “like follow-up with the physician, like ongoing consideration to weight-reduction plan and train.”

“We take [off-label prescribing] very critically,” says Novo’s Moore. “It’s the physician’s resolution how they will prescribe medication. However it’s our job to make sure that we educate clinicians across the protected use of our medicines on label.” He says the corporate provides “course corrections” when particular person prescribers don’t observe correct tips however declined to explain any such particular examples.

The urge for food for semaglutide within the U.S., in the meantime, seems insatiable. In Could, going through shortages, Novo Nordisk introduced that it was quickly pausing a few of its promotional efforts for Wegovy to keep away from “stimulating additional demand.” It was a performative gesture, given the larger image: From January to the tip of July 2023, in accordance with MediaRadar, Novo’s advert spending was up 23% for Ozempic and greater than 1,000% for Wegovy. The genie was already out of the vial. 

Semaglutide medication might be transformative, even life-changing—for sufferers who’re in a position to get and pay for a prescription. Greater than 70% of semaglutide prescriptions within the U.S. have gone to white sufferers, in accordance with information from Epic Analysis. White individuals are about 4 occasions extra probably than Black folks to have a prescription for a semaglutide, regardless of having practically a 40% decrease prevalence of diabetes and a 17% decrease prevalence of weight problems. In New York Metropolis, an analysis by Trilliant Well being for the New York Instances discovered that the very best charges of prescribing for Ozempic, Wegovy, and Eli Lilly’s Mounjaro in 2022 had been within the wealthiest—and healthiest—neighborhoods.

The explanation for that disparity is straightforward: Along with being remarkably efficient, Novo’s semaglutide merchandise are remarkably costly, at the least within the U.S. Right here, Wegovy prices at the least 4 occasions what it does in Europe. With a median U.S. record value of $1,349 for a four-week provide, a yr’s provide can price $16,000 or extra. And to take care of weight reduction, the medication should be taken indefinitely. Ozempic’s record value, in the meantime, is between $900 and $1,000 for a four-week provide. 

Novo’s Jørgensen defends the value by explaining that within the U.S., there’s the record value for a drug, after which there’s what clients really pay after insurance coverage. “We give, on common, 75% in rebates” throughout the corporate’s drug portfolio, he says. In accordance with evaluation from the American Enterprise Institute, insurers pay Novo about $700 for a four-week provide of Wegovy and about $300 for Ozempic. On its most up-to-date earnings name, Novo reported that People with insurance coverage that covers Wegovy normally pay lower than $25 a month for the remedy. 

However many insurers are pulling again and rethinking protection. “There was manner an excessive amount of hype, and the medication are costly,” says a veteran New Jersey insurance coverage agent. “Insurers are avoiding [covering GLP-1s] whether it is solely for weight reduction.” 

A July survey by Discovered, an organization that gives obesity-care companies to 200,000 staff of enormous corporations, reported that 69% of its affected person inhabitants didn’t have protection for GLP-1 medication—a 50% decline since December 2022. Protection of Wegovy as an weight problems remedy within the Blue Cross and Blue Defend community, for instance, varies by regional plan and components in issues together with “regulatory necessities, employer preferences, and excellent affordability considerations,” in accordance with a spokesperson. Getting approval for off-label use of Ozempic for weight administration is even more durable, says the spokesperson: “We’re seeing sufferers utilizing [these medications] sooner than science can perceive their long-term effectiveness. Due to this uncertainty and the dearth of long-term proof, insurers could not cowl off-label use of weight administration right now.” 

Medicare sufferers, in the meantime, obtain no assist—the results of a 20-year-long prohibition on overlaying weight problems remedy. Novo has been working to muster assist for the Deal with and Cut back Weight problems Act of 2021, which might elevate the protection ban, and likewise donated to the Congressional Black Caucus Basis, the Asian Pacific American Institute for Congressional Research, and the Congressional Hispanic Caucus Institute, who again one other invoice on well being disparities that may scrap the ban. (In a doubtlessly extra controversial push to broaden entry, Novo has been working trials of each liraglutide and semaglutide weight-loss medication for youngsters as younger as 6 years previous; Eli Lilly is testing Mounjaro in the identical cohort.) 

However increasing entry is a troublesome promote: A current article within the New England Journal of Medication warned that if simply 10% of overweight Medicare beneficiaries had been to take Wegovy, it might price this system $27 billion a yr. Even in Denmark, the general public well being plan doesn’t cowl Wegovy, and the nation’s largest private insurer will cease reimbursements for the drug beginning in January. 

What finally brings down the value of semaglutide will likely be competitors. And it’s coming. This fall, the FDA accredited a higher-dose model of Eli Lilly’s Ozempic competitor, Mounjaro, to deal with weight problems. Marketed as Zepbound and launched in December, it provides superior weight reduction in comparison with Novo’s medication and a decrease record value, about $1,060.

At the very least 70 different weight-loss medication are in scientific trials, from Pfizer, Amgen, and a number of startups. Different pharma corporations are merely shopping for in. AstraZeneca paid $185 million final month for world rights to develop an experimental GLP-1 tablet from a Chinese language biotech, and Roche acquired California-based biotech Carmot Therapeutics, which has two weight problems drug candidates, for $2.7 billion. In July, Eli Lilly snapped up weight problems drugmaker Versanis in a deal price as much as $1.9 billion. In August, Jørgensen acquired two obesity-drug startups, Danish firm Embark and Montreal-based Inversago, in offers that could possibly be price greater than $1 billion. 

Novo’s weight-loss gravy practice could quickly gradual, however the firm is rapidly laying new observe. “We’re simply studying all of the organic methods the place GLP-1 agonists can play a task,” says Marcus Schindler, Novo Nordisk’s government vp for analysis and early growth and chief scientific officer. And Novo has arguably dedicated essentially the most assets and time to figuring them out. 

Novo lately launched information from a trial of Ozempic in folks with power kidney illness and diabetes that confirmed a 20% discount within the danger of dying from kidney and coronary heart issues. Different initiatives are investigating GLP-1s for osteoarthritis, Alzheimer’s illness (in a Phase 3 trial), and NASH (nonalcoholic steatohepatitis), a type of fatty liver illness. A College of Oklahoma research taking a look at semaglutide as a remedy for alcohol use dysfunction is at present enrolling sufferers.

Coronary heart illness is one other main focus for the corporate. Cardiac medication, in any case, are a giant market—price $48 billion worldwide by 2026, in accordance with some estimates—and they’re exhausting for insurers to jot down off as nonessential. After seeing early proof of Ozempic’s potential to handle coronary heart issues, Jørgensen made a calculated guess and and launched a large-scale trial to look at the cardiovascular functions. 

Launched final month, the outcomes from the practically five-year research, which started enrolling sufferers in 2018, wowed scientists and buyers. In comparison with a placebo, Wegovy lowered the danger of a nonfatal coronary heart assault by 28%, and the danger of development of power kidney illness and renal dying by 22%. It diminished the danger of heart-related dying by 15% and the danger of dying by any trigger by 19%. It additionally reduce the danger of creating diabetes by 73% and the danger of nonfatal stroke by 7%.

The corporate expects an expanded FDA approval of semaglutide for coronary heart illness within the first half of 2024, which might be one other sport changer for the corporate. “Cardiologists began being serious about GLP-1s,” says Jørgensen. “The entire medical understanding of the hyperlink between weight problems and diabetes, heart problems, hypertension, and all of those cardiometabolic ailments is being understood now.”

Novo has been ramping up its R&D spending, allocating greater than $3.5 billion in 2022, up from about $2.6 billion the yr earlier than. Within the 12 months ending September 30, it plowed $4.32 billion into analysis—a 37% enhance yr over yr. Lots of the firm’s investments are geared towards compressing the time it’ll take to establish and validate the subsequent blockbuster, no matter comes after GLP-1s. One in every of Schindler’s massive goals is to take concepts to human testing sooner. “Testing novel ideas and molecules in animals excessively or for too lengthy doesn’t make us clever,” he says. “It’s the human information that really matter.” 

Shortening the trail to people means, amongst different issues, doing extra to automate early analysis. In a tour of the corporate’s sprawling labs in suburban Måløv, Denmark this fall, a number of Novo researchers confirmed off the robotic gear and extremely automated processes that enable the corporate to quickly design, synthesize, and check new peptide and protein formulations for next-generation medication. AI is one other precedence. “Quite than iterative cycles of animal research, doing one four-week experiment after the opposite, we are able to [use AI to] mannequin these outcomes,” Schindler says. “We are able to  contract the timeline to determine a brand new chemistry] from months or years earlier than, to days.” 

Novo can be beginning to look exterior its labs for innovation. In September, it introduced a collaboration with MIT-Harvard’s Broad Institute to establish new drug targets. A further partnership with Cambridge-based enterprise agency Flagship Pioneering goals to have interaction their portfolio corporations in engaged on a number of the issues that Novo is attempting to unravel. 

“Historically, Novo Nordisk has been very a lot centered round Denmark and the Danish workforce,” says Schindler. Because it enters the ranks of the pharma elite, the corporate is performing increasingly more like the worldwide big that it’s. 

Like different giant Danish corporations—together with Lego, beer maker Carlsberg, and delivery line Maersk—Novo Nordisk is majority-controlled by an unbiased basis whose objective is to offer a secure foundation for the business and analysis actions of corporations within the Novo Group (consisting of Novo Nordisk and Novozymes, a maker of business enzymes), and to assist scientific, humanitarian, and social causes. The construction is designed to assist a extra long-term administration perspective, explains Jørgensen. “We consider course in delivering right here and now, however equally we predict in many years ahead,” he says.

As a result of it’s one of many nation’s largest employers and company philanthropists, and since so many Danish pension funds maintain firm inventory, what’s good for Novo has typically been seen nearly as good for Denmark. Whether or not it’s good for America is one other query.

People appear to want what Novo Nordisk is promoting. The corporate’s pipeline of merchandise couldn’t align extra completely with our nationwide illnesses of weight problems, diabetes, and coronary heart illness. However People’ starvation for immediate cures—and the federal government’s normal failure to rein within the prices of medication and the conduct of drug corporations and docs—may drive a state of affairs the place cash and a capability to govern the system decide entry to lifesaving remedy. That will sound dystopian. It could sound like enterprise as traditional.