For a society so fixated on body weight, we know shockingly little about how it works.
Obesity was formally recognized as a disease just a decade ago, in 2013. The medical designation was intended to distinguish excess weight as a complex, chronic illness, not a failing of personal willpower — though there was, and remains, some controversy around the term, with Latin roots meaning "to eat oneself fat."
The misconception that obesity is caused mostly by a lack of exercise — or that people with obesity pay no attention to their diet — is still deeply entrenched. Contrary to popular belief, obesity and related diseases like diabetes and hypertension are complex and cannot always be cured by simply moving more. The environment we live in, the chemicals we're exposed to, the stress we're under, and our unique brain circuitry all play roles.
Dr. Beverly Tchang, an endocrinologist at Weill Cornell Medicine, has spent the past seven years working to help her patients — and the society they interact with — view it as a medical condition like any other, requiring treatment, attention, and empathy.
Until recently, the main problem was that there had never been an effective nonsurgical way for patients with obesity to lose weight and keep it off, especially a lot of weight. Doctors may recommend a diet or exercise plan for a patient who has high cholesterol, high blood pressure, or high blood sugar, but research shows it's nearly impossible for someone to maintain a calorie deficit if their brain and body are against it. The patient inevitably ends up in a cycle of "yo-yo dieting" that doesn't do their metabolism any favors.
For a time, a medication approved by the Food and Drug Administration called Belviq seemed helpful, but it was pulled from the market in 2020 after it was linked to an increased cancer risk. Phentermine, once used in a widely prescribed appetite-control drug cocktail called fen-phen, is now doled out sparingly because it was linked in 2011 to a higher risk of heart disease and damage to the heart valves.
But in 2023, Tchang's work, and the entire world of obesity medicine, is completely transformed.
The moment everything changed
As is often the case in the slow moving world of medicine, the seeds of this transformation were planted several years earlier, in 2017, when the Danish drug manufacturer Novo Nordisk released Ozempic.
Ozempic is a once-a-week injection to treat type 2 diabetes. Its active ingredient, semaglutide, mimics GLP-1, a hormone that the gut produces naturally to help balance blood sugar. Whether produced by the body or by a shot like Ozempic, GLP-1 can help quiet the voice in your brain telling you to have just one more potato chip, another helping of dessert, or an extra treat between meals when your body doesn't need the fuel. It slows down digestion too, meaning people who take the drug stay both physically and mentally fuller for longer.
It worked brilliantly for diabetes control. But as Novo's researchers studied semaglutide, exploring higher and higher doses, they encountered a truly groundbreaking result: significant, lasting weight loss on a level that was once possible only with major surgery.
Ozempic was hardly the first medication of its class — GLP-1 agonists have been around since 2005. But this wasn't like liraglutide (sold as Saxenda), which needed to be injected daily, or dulaglutide (sold as Trulicity), which was good for managing blood sugar but didn't affect weight all that much. In Ozempic clinical trials, patients on semaglutide were losing previously unimaginable amounts of body weight — 10% in a matter of weeks or months.
The results supported the widely held theory among obesity specialists that "food noise," the persistent urge to keep eating to the point of weight gain, might be a matter of mismatched signals between the brain and body, rather than a question of willpower.
Ozempic's FDA approval in December 2017 sent a ripple of excitement through the US medical community. It was approved only to treat diabetes, but doctors have discretion to prescribe drugs for unapproved, "off-label" uses if they see fit. Comforted by more than a decade of safety research showing GLP-1 agonists to be low-risk medications, doctors started telling their patients with obesity about this once-a-week shot that melted pounds off. Patients who were previously reluctant to take mediocre, daily weight-loss medications were intrigued by these more powerful, elegant weekly drugs.
For doctors like Tchang, it made their jobs both easier and harder.
The rise and rise of weight-loss drugs hit a crescendo in 2023
Doctors were liberally prescribing Ozempic off-label for weight control for years, and seeing great results. It was an open secret among MDs. In the summer of 2021, the FDA approved Wegovy, another Novo Nordisk drug. It is essentially the same substance as Ozempic but contains a higher dose of semaglutide. This new formulation was specifically approved for weight management.
That's when these drugs started flooding into society. Prescriptions ticked up, and word spread far beyond the world of obesity medicine. By 2022, patients were starting to ask for Ozempic and Wegovy by name, citing TikTok videos describing "magical injections" that celebrities were thought to be taking to lose weight. The internet speculated (without evidence) that these shots were behind Kim Kardashian's dramatic and rapid weight loss.
At the same time, the rest of the pharma world was racing to catch up with Novo, whose success has single-handedly transformed the Danish economy. Eli Lilly produced Mounjaro, containing tirzepatide, which mimics GLP-1 and GIP, another appetite-regulating hormone, for a potentially greater effect. Mounjaro was FDA-approved as a diabetes drug in 2022. Like Novo Nordisk before it, Eli Lilly also started working on a weight-loss-specific, high-dose version of Mounjaro: Zepbound, which raced through the FDA approval process last month. Lilly is now working on a third drug, jokingly referred to as "the King Kong of weight-loss drugs'' because it contains retatrutide, which targets three hunger hormones.
Prescription rates exploded …
As shortages hit, clinics started making their own copycat "compounded" medications. The FDA allows this when there is a shortage, but there is little oversight and not much transparency about what these knock-off versions of the drug contain.
Uniquely, this all coincided with the COVID-19 pandemic, which forced the US into a new, uncharted world of telehealth. That made all drugs much easier to access than usual. "All of a sudden you have the outcropping of virtual care, and you have some people who want to make a business out of it and don't have that sort of evidence-based management style," Dr. W. Scott Butsch, director of obesity medicine at the Cleveland Clinic, told Business Insider.
Suddenly, you didn't need to ask your doctor to prescribe that weight-loss shot you'd heard about on TikTok; you could just go to one of those websites promoted on Instagram, fill out a cursory "exam" via Zoom, or even a Google form, and put in your credit card information. Within a few days, you would receive your medication.
This unofficial system perpetuated the weight-loss drug trend through the shortages of 2023, allowing people to use weight-loss drugs even if they couldn't find or afford brand-name versions.
"I walk around telling people, 'pinch me,'" Dr. Nadia Ahmad, the medical director of obesity-medicine development at Lilly, told Business Insider at the American Diabetes Association conference in June. "It's a historic, monumental time. There's so much hope for patients. There's so much hope for people who've been struggling with this chronic disease."
Talking to people who are taking GLP-1s, the hope and excitement are palpable. It is also tinged with some uncomfortable feelings and unanswered questions. Hear them in their own words …
The reality of living on GLP-1s
Jacob Brody, a 41-year-old venture capitalist in New York, has been taking Mounjaro for a little over a year. "I've never taken a medication that so fundamentally changed my life," Brody, who has both type 1 and type 2 diabetes, said.
It was like the flick of a light switch. Suddenly, weight he'd been putting on was coming off. Many of his other chronic health issues, like arthritis and back pain, were improving too. Having less belly fat made it easier and less painful to stretch out each morning. Worrying less about food left him more time for blogging and gardening.
It was uneasy, suddenly losing desires he had lived with for years. An apathy toward food derailed his daily life. Brody described a feeling of loss, and a sense of panic whenever he left food on his plate. His body wasn't hungry anymore, but his brain was still constantly asking: Will that be enough?
Over time, he felt that old food stress melt away. He started building a new routine: a protein smoothie in the morning, and dinner with his son. "I was actually able to build a bunch of other habits alongside it because I thought it was possible to be healthy," Brody said.
He feels better, happier. He's less explosive — something he attributes to no longer being in constant pain.
It's a welcome shift, but Brody craves professional support for the cognitive dissonance. Rewiring your brain is part of the deal, and he feels it's underappreciated that patients and doctors are learning about this phenomenon in real time.
Just like real hormones, these drugs have a multilayered influence on our bodies, slowing digestion and also influencing the brain's pleasure centers to tone down cravings. The rush Brody once got from a crunchy Cheez-It has vanished. Some people find their morning coffee becomes acrid. Many have reported losing any desire to drink alcohol — prompting some doctors to explore GLP-1s for treating addiction.
"Things that are pleasurable are no longer so pleasurable," Dr. Joseph Volpicelli, a psychiatrist in Plymouth Meeting, Pennsylvania, who researches addiction medication, previously told BI.
That goes for sex, too.
Ashley Dunham, 32, started taking compounded semaglutide to treat her polycystic ovarian syndrome, a hormonal imbalance that can include overproduction of testosterone, affecting insulin control and causing weight gain, painful periods, excess hair growth, or infertility. Dunham is effusive when she talks about her experience on semaglutide. She lost 70 pounds in six months and no longer struggles with irregular periods. Date nights are cheaper, too, because she's full within a few bites and not as interested in alcohol.
It's a net positive for Dunham, though the sudden lack of drive — to do work, to do laundry, to have sex — took her, and her husband of 10 years, by surprise.
On semaglutide, she has to tell herself when to eat, because her natural craving is muted. Sex is similar. Dunham said some of her girlfriends were taking GLP-1s too and had described a similar shift in libido.
Dunham has developed one urge she didn't have before: shopping. It's something to do with her hands in the evenings — she's replaced snacking with scrolling.
It's a rush, she says, because she has been "sized in." At her new weight, Dunham is comfortable shopping at places that she felt never catered to her body, like Lululemon. (For years, Lululemon steadfastly only designed clothes up to size 12; the brand recently added plus-size options.)
That's the rub. Weight loss is revered in our society, and it can be a thrill, being accepted in a way you never were in a bigger body. But it also feels incredibly uncomfortable seeing the world open up to you once you're in a smaller body.
For Tara Rothenhoefer, whose older sister died of obesity-related complications in 2018, Mounjaro felt like a lifesaver. She dropped from 342 pounds to 210 during an 18-month clinical trial sponsored by Eli Lilly, after a decadeslong cycle of unsuccessful diets and treatments that began when she was 13. After the clinical trial, she went on to lose even more weight once she was able to obtain a prescription for the drug.
Rothenhoefer, who's 47, felt transformed. She hadn't known what it was like to live without a persistent ache in her shoulders, knees, and ankles, or a nagging food noise that clouded out other thoughts.
She was also struck by how much attention and kindness she was receiving now that she was 200 pounds lighter. Sure, it was nice, but it laid bare a depressing truth.
Any unexpected emotional or physical discomfort from taking GLP-1s is worth it for Jeannette Simonton, a registered nurse who wants nothing more than to do her job. She says semaglutide allows her to care for patients, and walk around wards without incurring bone damage. That's if she can afford it.
Simonton is suing her insurer for access to GLP-1 drugs. Washington State Health Care Authority reserves use for patients with diabetes. Simonton says this is discrimination against people with her disease, obesity.
She's lost 80 pounds, first on Mounjaro, now on compounded semaglutide, to get to 189 pounds. Her prescription has been a significant financial burden without insurance coverage. At the same time, she was able to qualify for total knee-replacement surgery because of the weight loss.
"She has done phenomenal with her weight loss," said Simonton's doctor, Peter Billing, who prescribes her semaglutide. "But without the drugs, without Ozempic, she wouldn't have lost the weight." Billing performed bariatric surgery on Simonton when she weighed over 400 pounds a decade ago and has watched her adhere to programs like Weight Watchers. He says Ozempic has helped Simonton move past a weight "plateau."
Simonton knows what you may be thinking, by the way. She sees the judgmental comments from people online, telling her to just "get out and exercise more." For Simonton, knee issues have often made walking nearly impossible.
Simonton pays about $200 a month out of pocket for semaglutide, which she has to dose into a needle herself. She stocks her fridge with a month's worth of the drug, just to be safe given the supply shortages.
Some people are trying to cut costs by tapering their use. Rothenhoefer, who cannot afford $1,000 a month for Mounjaro, is trying to save the few pens she has left, using it only when the food noise gets too overwhelming. Her most recent dose was over one month ago.
It's not unheard of — Oprah Winfrey told People she used a GLP-1, but only occasionally: "I now use it as I feel I need it, as a tool to manage not yo-yoing." But some doctors have reservations. Dr. Shalender Bhasin, who covers diabetes and endocrinology at Brigham and Women's Hospital, says going on and off GLP-1s might actually lead to yo-yoing weight, or might inflict damage we don't yet appreciate.
"Epidemiologic studies have shown that people who have this yo-yoing of their body weight — weight regain followed by weight loss, weight regain — is associated with higher mortality than weight stability, even if people are obese," Bhasin told BI.
Simonton refuses to become an experiment.
(Simonton's insurer declined to comment for this story, citing the ongoing litigation.)
You'd be forgiven, at this point, for thinking these are miraculous drugs. Even doctors at typically mild-mannered professional conferences have erupted into cheers, gasps, and applause when new GLP-1 data is announced. But not everyone is so elated with their results on the drugs.
Blake, a 38-year-old father of three, says his life has been changed forever because of just two doses of Mounjaro he took in late June and early July of this year. Blake, who asked BI to withhold his last name for privacy, said he wasn't looking for weight loss; his doctor recommended the weekly shot to control his blood sugar.
Blake's voice has been digitally altered:
A couple of days after his second dose of Mounjaro, Blake started to feel sick at work, and before he could make it to the bathroom he projectile-vomited everywhere, Blake told BI. Then the vomiting continued, nonstop, he said. It wasn't until the next day, when Blake passed out from dehydration in urgent care, that he was taken to the emergency room. After roughly 10 days of tests, Blake was given a diagnosis of stomach paralysis, or gastroparesis.
Blake is the main breadwinner in his family, and he says he took a financial hit when he was out on medical leave, having to borrow money from family to pay utility bills for a few months.
A Southern, self-described "meat-and-potatoes guy," Blake is now avoiding many foods he once loved, like chicken and steak, to manage his condition. He says he can no longer tolerate metformin, the diabetes drug he used to take before trying Mounjaro, so he's started taking insulin to manage his type 2 diabetes.
Sometimes, he says, the vomiting or diarrhea he experiences as a result of his new condition comes on so suddenly he can't control his bowels and he has to leave work and clean himself up. "You just hope, I guess, the good days outweigh the bad days, but the bad days will happen," he said. "You just have to ride 'em out."
The personal-injury law firm Morgan & Morgan, which is handling Blake's case, told BI that their firm had screened more than 10,000 gastroparesis cases that might be related to GLP-1 drugs and were under active investigation. More than a dozen of those cases, including Blake's, have led to lawsuits in the US, claiming that Novo Nordisk (the maker of Ozempic and Wegovy) and/or Eli Lilly (Mounjaro and Zepbound) failed to properly warn patients and doctors of the risk of stomach paralysis.
Novo Nordisk and Eli Lilly both assert that slowing down the stomach is part of how these drugs work. Their product labels state the risk of delayed gastric emptying. Besides, diabetes can seriously mess with your digestion; it is the most well-known cause of gastroparesis.
A spokesperson for Eli Lilly told BI that "Mounjaro's label warns that use of Mounjaro may be associated with gastrointestinal adverse reactions, sometimes severe," and shouldn't be used in patients with severe gastrointestinal disease.
Doctors say the weight-loss drug trend needs to slow down
Gastroparesis is not the only uncomfortable concern surrounding GLP-1s.
European Union regulators are investigating 150 cases of suicidal thoughts possibly linked to use of Wegovy, Ozempic, and Saxenda.
And then there's the question of how this works in children. Kids as young as 12 are being prescribed GLP-1 drugs to treat PCOS, obesity, and diabetes — and their parents don't have a road map. How does this work on the developing brain? Should kids plan to taper off these drugs, and, if so, when and how? Novo Nordisk and Eli Lilly assure parents that they are testing their weight-loss drugs on kids as young as 6. Which prompts another question: Is this how we want to handle weight control in our kids? Are we banking on a prescription to circumvent all the systemic factors steeped against kids' health, including weight stigma?
The pharmaceutical industry has a fairly uniform response to any concerns about GLP-1s. These are well-tolerated drugs, with huge potential benefits, and adverse reactions are rare. Above all, they say, these drugs have solved a question at the heart of a touchstone culture war in America: what obesity is and how to fix it. "It's bigger than me" is the slogan of Novo Nordisk's ad campaign, featuring Queen Latifah.
Plus, research funded by Novo Nordisk and Eli Lilly suggests these drugs may reduce one's risk of heart disease, colon cancer, kidney failure, and hypertension.
Doctors generally agree that these drugs are helping many patients. But some also wish we could pull the brakes a little. GLP-1s are so popular that people are getting knock-off versions online, whether a doctor would recommend it or not, and taking them without medical supervision.
GLP-1s are designed (like other drugs) to stop working shortly after you stop taking them. To sustain the stunning weight loss and health effects of these drugs, most patients will probably have to take their medication for life. That throws up big, as-yet-unanswerable questions: What are the physical effects of this drug in the long term? What happens when patients start to build a tolerance to their weight-loss drug? How do we expect patients to afford the official, FDA-approved versions of these drugs in the long term? Are we prepared for society, sold on the benefits of GLP-1s, to go rogue, buying cheap versions online, and experimenting with spaced-out doses, without medical assistance?
Sometimes, harm isn't immediately apparent. A high-profile longevity physician, Dr. Peter Attia, posted a viral Instagram Reel earlier this year warning that he was concerned about rapid muscle loss among patients he'd spoken with. "They've lost muscle mass at a rate that alarms me," he said.
Bhasin shares Attia's concern, particularly for older or disabled patients, who are among those most in need of obesity drugs. Bhasin studies the cascading effects of losing muscle mass. Aside from making you feel weaker, muscle loss can also lead to bone loss and osteoporosis, increasing the risk of bone fractures from minor falls or exercise, Bhasin explained. Muscle loss can also damage metabolic function, potentially slowing fat loss.
Millions of people are already using these drugs. It isn't just people who have a genuine, diagnosed medical condition that affects their weight. It's healthy people with bigger bodies who are shamed by society. People who are tired postpartum and just want to lose their baby weight already. Teens who are bullied as their bodies develop. Anyone who wants to look more like the edited Instagram models they're bombarded with daily. Anyone who lives in a part of the US where healthy, unprocessed foods are inaccessible and most time outside the home is spent in a car.
GLP-1 drugs are starting to look like an individual Band-Aid for a society that's deeply sick. People are getting second or even third jobs to afford these drugs that they believe will make them look and feel healthier — spending over a thousand dollars a month in an effort to correct for problems that are much bigger than any of us.
2024, the beginning of a complex future for weight-loss drugs
The weight-loss-drug boom has, to date, been buoyed by the pharmaceutical industry. The drugs' manufacturers have been dishing out coupons for patients to try Wegovy, Mounjaro, Zepbound, and Ozempic at a discount. They have also been running clinical trials, which give patients an opportunity to try the drug for a year or more at no cost.
Now, the pressure on health insurers, employers, states, and Medicare to pay for these drugs is building. Patients and doctors are urging them to provide coverage.
Pharma companies are weighing in, too. They're trying to convince insurers that their drugs improve people's health beyond weight loss — and therefore could cut how much they spend on patients' weight-related conditions over time.
But many companies and other payers aren't yielding, keeping the expensive drugs out of reach. In a recent survey by the employee-benefits firm Mercer, 19% of US companies said they were considering adding coverage, but a larger chunk — 40% — said they had no plans to pay for the drugs. "Many just don't have the budget," said Renee Rayburg, a consultant at Pharmaceutical Strategies Group who works with employers on their pharmacy programs.
Terrified of seeing their health-plan costs soar, many companies are instead making it harder for people to get their hands on weight-loss drugs. They started by cracking down on use of Ozempic by people without type 2 diabetes. Now some are trying to restrict weight-loss drugs to people with higher BMIs, or to those who also participate in a behavior-change program. Some are limiting how long members can take the drugs — the Mayo Clinic told workers that, starting in 2024, it planned to cap lifetime spending on weight-loss drugs at $20,000 per health-plan member. Other employers, including the University of Texas System, are ending coverage altogether.
Government health plans aren't rushing to cover them, either, and the law prohibits Medicare from covering weight-loss drugs. That could change, but it would require Congress to act. And though there's been heavy lobbying from drugmakers and patient advocacy groups on that front, analysts at Capital Alpha Partners predict Medicare won't cover the drugs even partially until at least 2027.
Those barriers won't stem the flow of weight-loss drugs into society. The dam has been broken — patients and doctors have gotten a taste of how revolutionary these drugs could be.
Without institutional support, Tchang fears we may simply reinforce the same societal issues that made Ozempic such a hit. On the well-heeled Upper East Side, where Tchang works, prescriptions for GLP-1s abound. Many of her patients there are using GLP-1s as preventive medicine, battling against a family history of obesity, or hoping to correct a weight that's been slowly creeping higher and higher with age. Tchang hopes that one day we will all have the opportunity to approach our health like that. That's not our reality, though.
Design and development by Annie Fu. Photo editing by Isabel Fernandez-Pujol.