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BIGGEST LOSER

A new generation of weight loss drugs makes bold promises, but who really wins?

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In the months after having her second child, Sarah found herself fed up. The 40-year-old Seattle resident was cutting carbs and sugar, and exercising regularly, but couldn’t seem to shed the pounds she had put on during pregnancy. So when an email newsletter mentioned a new weight-loss drug called Wegovy, Sarah decided to give it a try. Eight months later, she is out more than $10,000—and down more than 60 lbs.

“Wegovy made losing weight almost effortless,” Sarah, whose name has been changed to protect her identity, told Quartz. “I’m not hungry often anymore and it doesn’t take any willpower to eat less. I simply don’t have any desire to overeat.”

Sarah is one of 125,000 US-based patients now taking Wegovy (whose generic name is semaglutide), a member of a new class of weight-loss drugs. These drugs work differently than the appetite suppressants popular among previous generations of dieters. They are also hitting the market at a different moment: one in which people are more eager than ever for realistic, science-based methods for addressing excess weight, even as a growing faction of activists and doctors voice skepticism of weight as an accurate measure of health.

A new class of weight-loss drug

In the mid-1990s, experiments on Gila monster venom found it contained hormones that could help lower blood sugar. That led to the diabetes drug Ozempic, which ultimately went on the market in 2018. People on that drug discovered a funny side effect: They lost weight.

In 2021, that same compound was approved by the US Food and Drug Administration (FDA) under the name Wegovy for the express purpose of weight loss. Drugs like Wegovy work in more complex ways than simply suppressing appetite, and promise fewer (though not zero) side effects.

Like Wegovy, many of these drugs were originally approved for other conditions; liraglutide (brand name Saxenda for weight loss) was also originally approved as a diabetes drug (Victoza). In fact, semaglutide and liraglutide work similarly in the body: They’re known as GLP-1 receptor agonists because they activate receptors for the glucagon-like peptide-1 (GLP-1) hormone, reducing appetite by slowing digestion and the rate at which the body takes up glucose.

Perhaps most important, the new drugs promise significant weight loss. “The previous weight loss drugs were just modestly effective,” says John Buse, an endocrinologist at the University of North Carolina School of Medicine. The average patient would lose 5% of their body weight, in some cases up to 8%. But with semaglutide, he says, “we’ve gotten the kind of weight loss that makes people pay attention: 10-15% of body weight. That’s the average weight loss—half of people are losing more than that. It’s a gamechanger in the conversation…now that we have medicines for which a substantial proportion of patients can expect to lose 30 to 50 lbs.”

In one 68-week pre-approval clinical trial, patients on Wegovy did indeed lose 14.9% of their body weight on average, compared with 2.4% for people on a placebo. (Although, as several writers and scholars have pointed out, the study was funded by Novo Nordisk, which makes Wegovy.) Given the average weight of trial participants—100 kg, or 220 lbs.—that meant weight loss of about 15 kg, or 33 lbs.

Other drugs in development have had similar results. In a recent trial for one called tirzepatide from Eli Lilly, more than half of patients lost at least 20% of their body weight—50 lbs. in many cases.

What it takes to lose weight

This new class of drugs is entering a market that at first glance seems ripe for breakthrough. According to the US Centers for Disease Control and Prevention (CDC), 42% of Americans—70 million people—meet the criteria for obesity (having a BMI of 30 or more). At one point or another, most of those people will try a diet and exercise regimen to lose weight.

But a growing body of research shows that diets are not an effective way to lose weight and keep it off. “Obesity is a complex disease… ​for most people, lifestyle modifications, diet, and exercise are just not enough,” says Katherine Saunders, a doctor at the Comprehensive Weight Control Center at Weill Cornell Medicine and co-founder of Intellihealth, an app-based platform that brings evidence-based obesity treatment to patients.

In part because of that complexity, bariatric surgery has since 2009 been considered the standard of care for patients looking to lose a substantial amount of weight. But these procedures can be invasive and expensive, and can come with significant and long-lasting complications.

The dearth of other options leaves some patients and doctors excited about this new generation of drugs. “Right now, the field is really looking for more efficacy, number one. People will do almost anything to lose weight,” says Buse. “We have more than just surgery now for promoting substantial weight loss. The most exciting thing is that obesity is on the ropes.”

A complicated picture

While hopes are high, the realities of taking these drugs can be more complicated for patients. There are often side effects—the most common for semaglutide and liraglutide are diarrhea, vomiting, and nausea. On Wegovy, Sarah says she’s experienced diarrhea so severe that a few times she had to delay her next dose.

Physicians can sometimes gloss over or downplay those effects. But a visit to dedicated Reddit pages for these drugs shows whole communities of patients struggling to adhere to the regimen when they’re feeling sick, and seeking support from a community to understand whether what seems like a severe reaction is normal. (Novo Nordisk did not respond to a request for comment.)

How well a patient can tolerate a drug “is something we think about quite a lot,” Saunders says. “We always start with lower doses and increase gradually as tolerated. Everyone is different. We keep in close touch with the patient and monitor them closely.”

And while these new drugs are relatively well-studied, there are still unknowns. They seem to help patients keep weight off more reliably than diet and exercise alone, but those benefits fade after people stop taking the drugs, and patients do often regain weight. There are also questions about long-term effects. In 1997, weight loss drug fenfluramine/phentermine (fen-phen) was pulled off the market after it was found to cause heart problems. More recently, Belviq (lorcaserin), which the FDA approved for weight loss in 2012, was pulled from the US market in 2020 because long-term use was found to increase the incidence of various types of cancers.

Even if a patient does want to go on one of these drugs, she might not be able to. Many patients keen to try Wegovy can’t access it at the moment, due to a supply chain issue that its manufacturer doesn’t expect to resolve until later this year. Even then, most US health insurers, including Medicare, do not cover drugs like Wegovy, and paying out of pocket can cost thousands of dollars per month. After Sarah’s doctor told her she doesn’t prescribe Wegovy, Sarah secured a prescription through an online health provider; she pays for it out of pocket.

The lack of insurance coverage is in spite of the fact that the American Medical Association declared obesity to be a disease in 2013. “The conversation around insurance coverage needs to be had with insurance companies, but also with employers,” says Kimberly Gudzune, the medical director for the American Board of Obesity Medicine. “It needs to be seen as an investment in your workforce.” The Treat and Reduce Obesity Act, which would expand Medicare to include obesity treatments, has been introduced to US Congress every year since 2012, but has never passed.

America’s love/hate relationship with weight

Though excess body fat was once considered a sign of wealth or fertility, over the past century a stigma has developed against larger bodies. Today doctors associate excess weight with medical conditions like heart disease, cancer, type 2 diabetes, sleep apnea, osteoarthritis, and depression. Studies also show that life is harder when you move through the world in a larger body. Fat people are less likely to be hired for a job, are paid less, are less likely to get married, and are less likely to be happy (though not if they’re living around other fat people). One 2006 study found that 46% of respondents would rather give up one year of life than be obese; 5% said they’d rather lose a limb.

The current state of research makes it impossible to unravel the full complexity of weight and health, but the conversation is starting to accommodate more nuance. Ubiquitous metrics such as body mass index are increasingly understood to be unreliable indicators (though doctors often still use them), and even the language around larger bodies is under review. Many physicians use “obese” to describe people who have excess weight or a BMI over 30, but activists are shying away from the word. “The reason…we are reluctant to use the words ‘overweight’ and ‘obesity’ is that they are made up, they can change,” says Tigress Osborn, a fat activist and chair of the National Association to Advance Fat Acceptance.

In fact, some research suggests that fat may have a protective effect on the body. “The body’s weight-regulating mechanism is about survival. It’s a system with more moving parts than we understand,” says Marilyn Wann, a fat activist and author of the book Fat!So? “Trying to remove weight from an individual or from the population is like trying to take a sledgehammer to the weather—we don’t know the unintended negative consequences we’re going to create.”

There are signs that in the future physicians may be more accepting of bodies of different sizes. But as weight loss drugs get more effective and more available, those cultural gains for body positivity (or body neutrality, or fat acceptance) may also be called into question.

A new relationship between doctors and patients

Overweight patients who come to see Shelly Crane might have an experience they’ve never had before. “I don’t initiate a weight-loss conversation with a patient,” says Crane, a family physician at Advocate Aurora Health in Milwaukee, Wisconsin. Most weight-loss programs come with more risk of harm than good, she says, and there’s not enough evidence that people who do lose weight are healthier in the end.

Crane doesn’t regularly prescribe new drugs for weight loss, though she says more patients are coming in and asking for them lately. Instead, she prefers to keep conversations focused on goals of care. “Patients say, ‘I know I need to lose weight,’ and I say, ‘Why do you think you need to lose weight? What would change in your life if your weight was lower?’” That gives her an opening to talk about health more broadly—how is the patient’s sleep? Their diet? Their mobility? “I try to stay in my sphere of what I’m able to do as a family doctor and really address the root of the health issue as much as I can.”

Crane was drawn to this approach by listening to her patients talk about experiencing size discrimination, and by following the work of fat activists such as Ragen Chastain and Aubrey Gordon. Though she’s been trained in a more integrative style of medicine, her approach toward body acceptance was also shaped by her discovery of intuitive eating during medical school. Since then, she’s been working on deprogramming herself and her colleagues from anti-fat bias.

Crane is part of a burgeoning movement among doctors to improve the treatment of larger patients. For some, that means skipping the dreaded weigh-in, a practice that is somewhat controversial within medicine. Medical organizations like the Association of American Medical Colleges also offer guidelines to reduce anti-fat bias among clinicians.

For doctors, the updated approach at least engenders trust, which can in turn get patients to seek medical care more frequently and improve their overall health. At most, it broadens the definition of what “healthy” means, and looks like.

Some fat activists see this shift as an important step. “The thing we hear most often from the public is, ‘I thought I had this thing, but all the doctor wanted to talk to me about is weight loss, and now the thing is worse,’” Osborn says. “It’s progress to have people in the medical establishment recognizing that there are other healthcare concerns besides weight, if weight is a healthcare concern.”

The hope is that this evolution continues. Activists want more people, in the medical profession and outside of it, to respect their autonomy. That becomes even more pressing in a possible future filled with weight-loss drugs—a future where a person can simply take a drug and stop being fat. “The ease with which I could become smaller—why should I? That should be up to me. Just like, if you believe it’s a medical disorder, the treatment I choose should be up to me,” Osborn says. “Like with anything else, if you believe fat is a disorder, we should let people decide whether people will get treated or not.”

“Fatness isn’t a problem to be solved in and of itself. It is not the root cause of all ills, as much as [medicine] would like to think it is,” Crane says. “We can help people live full, rich lives when we focus on goals of care and not on weight.”

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