The Problematic Arrival of Anti-Obesity Drugs
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science
Jan 2023
A new wave of medicines that treat obesity have taken the world by storm and been met with applause, concern, and abuse.
These are "breakthrough drugs," writes Eric Topol, a professor of molecular medicine at Scripps Research and one of the best known practicing scientists in the United States. "While there are many drawbacks, we shouldn't miss such an extraordinary advance in medicine--the first real, potent, and safe treatment of obesity."
Novo Nordisk's semaglutide (also known as Wegovy or Ozempic) was approved as an obesity treatment in adults back in June 2021 in the US and in early 2022 in the United Kingdom and the European Union. At the end of 2022, the US Food and Drug Administration also approved it for treating obesity in children aged 12 and up. On its heels, Eli Lilly's tirzepatide (or Mounjaro)--approved for treating diabetes--is likely to be authorized for treating obesity in the US later this year. It's already being prescribed off-label for that purpose.
Developed about a decade ago, semaglutide works by stimulating the hormone GLP-1, which prompts the body to pump out more insulin (like tirzepatide, it began as a treatment for diabetes). Tirzepatide also stimulates GLP-1, along with a hormone called GIP that likewise leads to insulin secretion. Both drugs work to provide a sense of fullness. In clinical trials, the treatments--delivered by weekly injections for 15-16 months--reduced body weight substantially: On average, those receiving semaglutide lost around 15 percent of their body weight, those on tirzepatide roughly 20 percent. In conjunction with the shots, participants in both trials were supported to adhere to a reduced-calorie diet and get 150 minutes of exercise a week.
The success--and mushrooming popularity--of these drugs brings us to a crossroads. We can make bigger bodies smaller with them, but does that mean we should? They promise to help people whose weight poses a health risk. And by shedding more light on what drives obesity, they could also chip away at harmful stereotypes that being overweight is simply a personal failing. At the same time, framing fatness as a disease to be done away with could lead to even greater stigma--as well as turbocharging society's obsession with thinness.
Members of the fat acceptance community--a decades-old social justice movement that has sought to reclaim the word "fat"--warn that these treatments risk entrenching the fat stigma that pervades society. Celebrating these drugs is "reinforcing for the general public the idea that fat is diseased and bad, and that we should be trying to eradicate fat people," says Tigress Osborn, the chair of the National Association to Advance Fat Acceptance (NAAFA). (People within the fat activist community prefer the term "fat," as they view "obesity" as a medicalized term that pathologizes bigger bodies.)
The activists fear that fat people may feel pressured to take these medications in order to access the same rights as their non-fat counterparts, rather than out of any desire to improve their health. "Is it really about health improvement when a person is experiencing daily weight stigma and feeling shamed and blamed and is looking for a solution to decrease the influence of that in their life?" says Sarah Nutter, a psychologist at the University of Victoria in Canada who specializes in weight stigma and body image.
To go through life in a fat body means you are less likely to be hired for a job and will be paid less than non-fat people. The effects of weight discrimination--which can include poorer medical treatment, loneliness, psychological distress, and increased stress--may actually be cutting short the lives of fat people.
Deciding whether to take the drugs becomes a "devil's choice," says Osborn. "Assert that I have the right to be as I am right now--or exchange that right for significantly more rights and privileges in the culture." The fat acceptance movement instead pushes for fat people to be afforded the same rights as everybody else, regardless of size.
Novo Nordisk's campaign "It's Bigger Than Me," with actor Queen Latifah as its face, has drawn particular criticism. Through it, the company is trying to align itself with the talking points of fat acceptance--eliminating weight stigma and bias and shattering the misconception that obesity is simply a lack of willful control--while at the same time selling a drug that has the goal of making fat people smaller. "By saying that if you take away the fatness, you're giving them the chance to thrive, you're not--you're just making the person smaller, and you're selling them smallness as a gateway out of oppression," says Marquisele Mercedes, a doctoral student in public health at Brown University.
Yet these concerns are opposed by an obvious truth: Anti-obesity drugs are effective at tackling what is a complicated condition. While the underpinnings of obesity remain elusive, a colliding consensus among researchers has landed on one irrefutable fact: Obesity is not a physical manifestation of an absence of willpower. Research has proven, repeatedly, that dieting doesn't work to reduce weight and keep it off. Obesity is a complex, entangled mishmash of biological and environmental factors that scientists have yet to fully solve and which can't be boiled down to the simple matter of calories in, calories out. "That concept is wrong," says Francesco Rubino, a professor of metabolic surgery at King's College London. "It's not true that obesity is the consequence of too much energy."
Having working drugs that can step in where other interventions have failed will offer important health benefits for some. Obesity raises the risk of a number of debilitating and deadly conditions, including heart disease, diabetes, high blood pressure, stroke, and certain forms of cancer. These drugs could even help solve the mystery of the root causes of weight gain, Rubino says. On top of a reduced urge to eat, people who take semaglutide appear to have a lowered impulse to partake in dopamine-fueled behaviors, like drinking booze or shopping, according to David Macklin, a doctor who has treated many patients with the drug.
But these treatments aren't intended for the masses. They are indicated for a specific group of patients: people with a body mass index of 30 kg/m2, the clinical definition of obesity, or for people who have a BMI of 27 kg/m2 or higher (and so are classified as overweight) if they have another weight-related condition that threatens their health, such as high blood pressure. (It's worth mentioning that BMI, the diagnostic tool most commonly used globally to determine obesity, has been shown to be a flawed and discriminatory health metric.)
Unsurprisingly though, it hasn't taken long for people who don't fall into these categories to start taking the drugs for aesthetic reasons. In May 2022, Australian health authorities reported a widespread shortage of semaglutide, where it is still only used to treat diabetes, due to reports of people using it for weight loss. The shortage is so great that it will last until April 2023, leaving people who have diabetes without access. In the US, semaglutide is also a scarce commodity. Production problems are partly to blame, but the shortage is thought to have been exacerbated by a flurry of attention on TikTok--#Ozempic currently has about 433.5 million views on the social media platform. Semaglutide has been described as the worst-kept secret in Hollywood. Celebrities like Elon Musk have admitted to using it to slim down, and it's been promoted by celebrity television personality Dr Oz. It's become so in-demand that people are mixing the drug themselves at home using the raw ingredients purchased online.
There's also the looming unanswered question of how long people will have to take these drugs, owing to the strong likelihood that the weight will return when they cease treatment. Research has found that patients who stopped taking semaglutide and discontinued the supporting lifestyle interventions regained about two-thirds of their lost weight within a year. Given the probable need for patients to continue taking the drug, its price is no small issue: In the US, semaglutide costs over $1,000 a month, and Medicare, the government-provided health insurance program, doesn't cover it. As for long-term health effects, the brevity of the trials conducted so far can't tell us much, although Ozempic's website warns that potential side effects include thyroid tumors and pancreatitis.
None of these concerns have done much to dampen appetite for the treatments. Novo Nordisk is projected to pull in $3.5 billion this year from its versions of semaglutide. As for Eli Lilly's tirzepatide, it's estimated to bring the company $25 billion in annual sales if approved as a treatment for obesity, and it is projected to be "the biggest drug ever." If there were ever a time to reconsider whether these drugs should be embraced by the mainstream, this is that moment.
When the writer Roxane Gay wrote about her complicated decision to get weight-reduction surgery, she noted a depressing truth: "I had to accept that I could change my body faster than this culture will change how it views, treats, and accommodates fat bodies." With the arrival of anti-obesity drugs, it seems that the balance between accepting fat bodies and wishing to drive them out of existence is going to become even more skewed.
