Ozempic or Bust - The Atlantic - 0 views
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June 2024 Issue
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it is impossible to know, in the first few years of any novel intervention, whether its success will last.
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The ordinary fixes—the kind that draw on people’s will, and require eating less and moving more—rarely have a large or lasting effect. Indeed, America itself has suffered through a long, maddening history of failed attempts to change its habits on a national scale: a yo-yo diet of well-intentioned treatments, policies, and other social interventions that only ever lead us back to where we started
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Through it all, obesity rates keep going up; the diabetes epidemic keeps worsening.
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The most recent miracle, for Barb as well as for the nation, has come in the form of injectable drugs. In early 2021, the Danish pharmaceutical company Novo Nordisk published a clinical trial showing remarkable results for semaglutide, now sold under the trade names Wegovy and Ozempic.
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Patients in the study who’d had injections of the drug lost, on average, close to 15 percent of their body weight—more than had ever been achieved with any other drug in a study of that size. Wadden knew immediately that this would be “an incredible revolution in the treatment of obesity.”
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Many more drugs are now racing through development: survodutide, pemvidutide, retatrutide. (Among specialists, that last one has produced the most excitement: An early trial found an average weight loss of 24 percent in one group of participants.
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In the United States, an estimated 189 million adults are classified as having obesity or being overweight
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The drugs don’t work for everyone. Their major side effects—nausea, vomiting, and diarrhea—can be too intense for many patients. Others don’t end up losing any weight
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For the time being, just 25 percent of private insurers offer the relevant coverage, and the cost of treatment—about $1,000 a month—has been prohibitive for many Americans.
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The drugs have already been approved not just for people with diabetes or obesity, but for anyone who has a BMI of more than 27 and an associated health condition, such as high blood pressure or cholesterol. By those criteria, more than 140 million American adults already qualify
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if this story goes the way it’s gone for other “risk factor” drugs such as statins and antihypertensives, then the threshold for prescriptions will be lowered over time, inching further toward the weight range we now describe as “normal.”
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How you view that prospect will depend on your attitudes about obesity, and your tolerance for risk
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The first GLP-1 drug to receive FDA approval, exenatide, has been used as a diabetes treatment for more than 20 years. No long-term harms have been identified—but then again, that drug’s long-term effects have been studied carefully only across a span of seven years
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the data so far look very good. “These are now being used, literally, in hundreds of thousands of people across the world,” she told me, and although some studies have suggested that GLP-1 drugs may cause inflammation of the pancreas, or even tumor growth, these concerns have not borne out.
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adolescents are injecting newer versions of these drugs, and may continue to do so every week for 50 years or more. What might happen over all that time?
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“All of us, in the back of our minds, always wonder, Will something show up? ” Although no serious problems have yet emerged, she said, “you wonder, and you worry.”
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in light of what we’ve been through, it’s hard to see what other choices still remain. For 40 years, we’ve tried to curb the spread of obesity and its related ailments, and for 40 years, we’ve failed. We don’t know how to fix the problem. We don’t even understand what’s really causing it. Now, again, we have a new approach. This time around, the fix had better work.
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The fen-phen revolution arrived at a crucial turning point for Wadden’s field, and indeed for his career. By then he’d spent almost 15 years at the leading edge of research into dietary interventions, seeing how much weight a person might lose through careful cutting of their calories.
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But that sort of diet science—and the diet culture that it helped support—had lately come into a state of ruin. Americans were fatter than they’d ever been, and they were giving up on losing weight. According to one industry group, the total number of dieters in the country declined by more than 25 percent from 1986 to 1991.
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Rejecting diet culture became something of a feminist cause. “A growing number of women are joining in an anti-diet movement,” The New York Times reported in 1992. “They are forming support groups and ceasing to diet with a resolve similar to that of secretaries who 20 years ago stopped getting coffee for their bosses.
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Now Wadden and other obesity researchers were reaching a consensus that behavioral interventions might produce in the very best scenario an average lasting weight loss of just 5 to 10 percent
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National surveys completed in 1994 showed that the adult obesity rate had surged by more than half since 1980, while the proportion of children classified as overweight had doubled. The need for weight control in America had never seemed so great, even as the chances of achieving it were never perceived to be so small.
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Wadden wasn’t terribly concerned, because no one in his study had reported any heart symptoms. But ultrasounds revealed that nearly one-third of them had some degree of leakage in their heart valves. His “cure for obesity” was in fact a source of harm.
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In December 1994, the Times ran an editorial on what was understood to be a pivotal discovery: A genetic basis for obesity had finally been found. Researchers at Rockefeller University were investigating a molecule, later named leptin, that gets secreted from fat cells and travels to the brain, and that causes feelings of satiety. Lab mice with mutations in the leptin gene—importantly, a gene also found in humans—overeat until they’re three times the size of other mice. “The finding holds out the dazzling hope,”
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In April 1996, the doctors recommended yes: Dexfenfluramine was approved—and became an instant blockbuster. Patients received prescriptions by the hundreds of thousands every month. Sketchy wellness clinics—call toll-free, 1-888-4FEN-FEN—helped meet demand. Then, as now, experts voiced concerns about access. Then, as now, they worried that people who didn’t really need the drugs were lining up to take them. By the end of the year, sales of “fen” alone had surpassed $300 million.
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It was nothing less than an awakening, for doctors and their patients alike. Now a patient could be treated for excess weight in the same way they might be treated for diabetes or hypertension—with a drug they’d have to take for the rest of their life.
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the article heralded a “new understanding of obesity as a chronic disease rather than a failure of willpower.”
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News had just come out that, at the Mayo Clinic in Minnesota, two dozen women taking fen-phen—including six who were, like Barb, in their 30s—had developed cardiac conditions. A few had needed surgery, and on the operating table, doctors discovered that their heart valves were covered with a waxy plaque.
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Americans had been prescribed regular fenfluramine since 1973, and the newer drug, dexfenfluramine, had been available in France since 1985. Experts took comfort in this history. Using language that is familiar from today’s assurances regarding semaglutide and other GLP-1 drugs, they pointed out that millions were already on the medication. “It is highly unlikely that there is anything significant in toxicity to the drug that hasn’t been picked up with this kind of experience,” an FDA official named James Bilstad would later say in a Time cover story headlined “The Hot New Diet Pill.
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“I know I can’t get any more,” she told Williams. “I have to use up what I have. And then I don’t know what I’m going to do after that. That’s the problem—and that is what scares me to death.” Telling people to lose weight the “natural way,” she told another guest, who was suggesting that people with obesity need only go on low-carb diets, is like “asking a person with a thyroid condition to just stop their medication.”
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She’d gone off the fen-phen and had rapidly regained weight. “The voices returned and came back in a furor I’d never heard before,” Barb later wrote on her blog. “It was as if they were so angry at being silenced for so long, they were going to tell me 19 months’ worth of what they wanted me to hear. I was forced to listen. And I ate. And I ate. And ate.”
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For Barb, rapid weight loss has brought on a different metaphysical confusion. When she looks in the mirror, she sometimes sees her shape as it was two years ago. In certain corners of the internet, this is known as “phantom fat syndrome,” but Barb dislikes that term. She thinks it should be called “body integration syndrome,” stemming from a disconnect between your “larger-body memory” and “smaller-body reality.
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In 2003, the U.S. surgeon general declared obesity “the terror within, a threat that is every bit as real to America as the weapons of mass destruction”; a few months later, Eric Finkelstein, an economist who studies the social costs of obesity, put out an influential paper finding that excess weight was associated with up to $79 billion in health-care spending in 1998, of which roughly half was paid by Medicare and Medicaid. (Later he’d conclude that the number had nearly doubled in a decade.
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In 2004, Finkelstein attended an Action on Obesity summit hosted by the Mayo Clinic, at which numerous social interventions were proposed, including calorie labeling in workplace cafeterias and mandatory gym class for children of all grades.
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he message at their core, that soda was a form of poison like tobacco, spread. In San Francisco and New York, public-service campaigns showed images of soda bottles pouring out a stream of glistening, blood-streaked fat. Michelle Obama led an effort to depict water—plain old water—as something “cool” to drink.
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Soon, the federal government took up many of the ideas that Brownell had helped popularize. Barack Obama had promised while campaigning for president that if America’s obesity trends could be reversed, the Medicare system alone would save “a trillion dollars.” By fighting fat, he implied, his ambitious plan for health-care reform would pay for itself. Once he was in office, his administration pulled every policy lever it could.
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Michelle Obama helped guide these efforts, working with marketing experts to develop ways of nudging kids toward better diets and pledging to eliminate “food deserts,” or neighborhoods that lacked convenient access to healthy, affordable food. She was relentless in her public messaging; she planted an organic garden at the White House and promoted her signature “Let’s Move!” campaign around the country.
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An all-out war on soda would come to stand in for these broad efforts. Nutrition studies found that half of all Americans were drinking sugar-sweetened beverages every day, and that consumption of these accounted for one-third of the added sugar in adults’ diets. Studies turned up links between people’s soft-drink consumption and their risks for type 2 diabetes and obesity. A new strand of research hinted that “liquid calories” in particular were dangerous to health.
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when their field lost faith in low-calorie diets as a source of lasting weight loss, the two friends went in opposite directions. Wadden looked for ways to fix a person’s chemistry, so he turned to pharmaceuticals. Brownell had come to see obesity as a product of our toxic food environment: He meant to fix the world to which a person’s chemistry responded, so he started getting into policy.
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The social engineering worked. Slowly but surely, Americans’ lamented lifestyle began to shift. From 2001 to 2018, added-sugar intake dropped by about one-fifth among children, teens, and young adults. From the late 1970s through the early 2000s, the obesity rate among American children had roughly tripled; then, suddenly, it flattened out.
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although the obesity rate among adults was still increasing, its climb seemed slower than before. Americans’ long-standing tendency to eat ever-bigger portions also seemed to be abating.
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sugary drinks—liquid candy, pretty much—were always going to be a soft target for the nanny state. Fixing the food environment in deeper ways proved much harder. “The tobacco playbook pretty much only works for soda, because that’s the closest analogy we have as a food item,
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that tobacco playbook doesn’t work to increase consumption of fruits and vegetables, he said. It doesn’t work to increase consumption of beans. It doesn’t work to make people eat more nuts or seeds or extra-virgin olive oil.
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Careful research in the past decade has shown that many of the Obama-era social fixes did little to alter behavior or improve our health. Putting calorie labels on menus seemed to prompt at most a small decline in the amount of food people ate. Employer-based wellness programs (which are still offered by 80 percent of large companies) were shown to have zero tangible effects. Health-care spending, in general, kept going up.
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From the mid-1990s to the mid-2000s, the proportion of adults who said they’d experienced discrimination on account of their height or weight increased by two-thirds, going up to 12 percent. Puhl and others started citing evidence that this form of discrimination wasn’t merely a source of psychic harm, but also of obesity itself. Studies found that the experience of weight discrimination is associated with overeating, and with the risk of weight gain over time.
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obesity rates resumed their ascent. Today, 20 percent of American children have obesity. For all the policy nudges and the sensible revisions to nutrition standards, food companies remain as unfettered as they were in the 1990s, Kelly Brownell told me. “Is there anything the industry can’t do now that it was doing then?” he asked. “The answer really is no. And so we have a very predictable set of outcomes.”
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she started to rebound. The openings into her gastric pouch—the section of her stomach that wasn’t bypassed—stretched back to something like their former size. And Barb found ways to “eat around” the surgery, as doctors say, by taking food throughout the day in smaller portions
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Bariatric surgeries can be highly effective for some people and nearly useless for others. Long-term studies have found that 30 percent of those who receive the same procedure Barb did regain at least one-quarter of what they lost within two years of reaching their weight nadir; more than half regain that much within five years.
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if the effects of Barb’s surgery were quickly wearing off, its side effects were not: She now had iron, calcium, and B12 deficiencies resulting from the changes to her gut. She looked into getting a revision of the surgery—a redo, more or less—but insurance wouldn’t cover it
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She found that every health concern she brought to doctors might be taken as a referendum, in some way, on her body size. “If I stubbed my toe or whatever, they’d just say ‘Lose weight.’ ” She began to notice all the times she’d be in a waiting room and find that every chair had arms. She realized that if she was having a surgical procedure, she’d need to buy herself a plus-size gown—or else submit to being covered with a bedsheet when the nurses realized that nothing else would fit.
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Barb grew angrier and more direct about her needs—You’ll have to find me a different chair, she started saying to receptionists. Many others shared her rage. Activists had long decried the cruel treatment of people with obesity: The National Association to Advance Fat Acceptance had existed, for example, in one form or another, since 1969; the Council on Size & Weight Discrimination had been incorporated in 1991. But in the early 2000s, the ideas behind this movement began to wend their way deeper into academia, and they soon gained some purchase with the public.
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“Our public-health efforts to address obesity have failed,” Eric Finkelstein, the economist, told me.
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Others attacked the very premise of a “healthy weight”: People do not have any fundamental need, they argued, morally or medically, to strive for smaller bodies as an end in itself. They called for resistance to the ideology of anti-fatness, with its profit-making arms in health care and consumer goods. The Association for Size Diversity and Health formed in 2003; a year later, dozens of scholars working on weight-related topics joined together to create the academic field of fat studies.
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As the size-diversity movement grew, its values were taken up—or co-opted—by Big Business. Dove had recently launched its “Campaign for Real Beauty,” which included plus-size women. (Ad Age later named it the best ad campaign of the 21st century.) People started talking about “fat shaming” as something to avoid
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By 2001, Bacon, who uses they/them pronouns, had received their Ph.D. and finished a rough draft of a book, Health at Every Size, which drew inspiration from a broader movement by that name among health-care practitioners
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But something shifted in the ensuing years. In 2007, Bacon got a different response, and the book was published. Health at Every Size became a point of entry for a generation of young activists and, for a time, helped shape Americans’ understanding of obesity.
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Some experts were rethinking their advice on food and diet. At UC Davis, a physiologist named Lindo Bacon who had struggled to overcome an eating disorder had been studying the effects of “intuitive eating,” which aims to promote healthy, sustainable behavior without fixating on what you weigh or how you look
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The heightened sensitivity started showing up in survey data, too. In 2010, fewer than half of U.S. adults expressed support for giving people with obesity the same legal protections from discrimination offered to people with disabilities. In 2015, that rate had risen to three-quarters.
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In Bacon’s view, the 2000s and 2010s were glory years. “People came together and they realized that they’re not alone, and they can start to be critical of the ideas that they’ve been taught,” Bacon told me. “We were on this marvelous path of gaining more credibility for the whole Health at Every Size movement, and more awareness.”
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that sense of unity proved short-lived; the movement soon began to splinter. Black women have the highest rates of obesity, and disproportionately high rates of associated health conditions. Yet according to Fatima Cody Stanford, an obesity-medicine physician at Harvard Medical School, Black patients with obesity get lower-quality care than white patients with obesity.
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That system was exactly what Bacon and the Health at Every Size movement had set out to reform. The problem, as they saw it, was not so much that Black people lacked access to obesity medicine, but that, as Bacon and the Black sociologist Sabrina Strings argued in a 2020 article, Black women have been “specifically targeted” for weight loss, which Bacon and Strings saw as a form of racism
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But members of the fat-acceptance movement pointed out that their own most visible leaders, including Bacon, were overwhelmingly white. “White female dietitians have helped steal and monetize the body positive movement,” Marquisele Mercedes, a Black activist and public-health Ph.D. student, wrote in September 2020. “And I’m sick of it.”
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Tensions over who had the standing to speak, and on which topics, boiled over. In 2022, following allegations that Bacon had been exploitative and condescending toward Black colleagues, the Association for Size Diversity and Health expelled them from its ranks and barred them from attending its events.
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As the movement succumbed to in-fighting, its momentum with the public stalled. If attitudes about fatness among the general public had changed during the 2000s and 2010s, it was only to a point. The idea that some people can indeed be “fit but fat,” though backed up by research, has always been a tough sell.
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Although Americans had become less inclined to say they valued thinness, measures of their implicit attitudes seemed fairly stable. Outside of a few cities such as San Francisco and Madison, Wisconsin, new body-size-discrimination laws were never passed.
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In the meantime, thinness was coming back into fashion
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In the spring of 2022, Kim Kardashian—whose “curvy” physique has been a media and popular obsession—boasted about crash-dieting in advance of the Met Gala. A year later, the model and influencer Felicity Hayward warned Vogue Business that “plus-size representation has gone backwards.” In March of this year, the singer Lizzo, whose body pride has long been central to her public persona, told The New York Times that she’s been trying to lose weight. “I’m not going to lie and say I love my body every day,” she said.
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Among the many other dramatic effects of the GLP-1 drugs, they may well have released a store of pent-up social pressure to lose weight.
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If ever there was a time to debate that impulse, and to question its origins and effects, it would be now. But Puhl told me that no one can even agree on which words are inoffensive. The medical field still uses obesity, as a description of a diagnosable disease. But many activists despise that phrase—some spell it with an asterisk in place of the e—and propose instead to reclaim fat.
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Everyone seems to agree on the most important, central fact: that we should be doing everything we can to limit weight stigma. But that hasn’t been enough to stop the arguing.
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Things feel surreal these days to just about anyone who has spent years thinking about obesity. At 71, after more than four decades in the field, Thomas Wadden now works part-time, seeing patients just a few days a week. But the arrival of the GLP-1 drugs has kept him hanging on for a few more years, he said. “It’s too much of an exciting period to leave obesity research right now.”
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When everyone is on semaglutide or tirzepatide, will the soft-drink companies—Brownell’s nemeses for so many years—feel as if a burden has been lifted? “My guess is the food industry is probably really happy to see these drugs come along,” he said. They’ll find a way to reach the people who are taking GLP‑1s, with foods and beverages in smaller portions, maybe. At the same time, the pressures to cut back on where and how they sell their products will abate.
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the triumph in obesity treatment only highlights the abiding mystery of why Americans are still getting fatter, even now
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Perhaps one can lay the blame on “ultraprocessed” foods, he said. Maybe it’s a related problem with our microbiomes. Or it could be that obesity, once it takes hold within a population, tends to reproduce itself through interactions between a mother and a fetus. Others have pointed to increasing screen time, how much sleep we get, which chemicals are in the products that we use, and which pills we happen to take for our many other maladies.
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“The GLP-1s are just a perfect example of how poorly we understand obesity,” Mozaffarian told me. “Any explanation of why they cause weight loss is all post-hoc hand-waving now, because we have no idea. We have no idea why they really work and people are losing weight.”
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The new drugs—and the “new understanding of obesity” that they have supposedly occasioned—could end up changing people’s attitudes toward body size. But in what ways
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When the American Medical Association declared obesity a disease in 2013, Rebecca Puhl told me, some thought “it might reduce stigma, because it was putting more emphasis on the uncontrollable factors that contribute to obesity.” Others guessed that it would do the opposite, because no one likes to be “diseased.”
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why wasn’t there another kind of nagging voice that wouldn’t stop—a sense of worry over what the future holds? And if she wasn’t worried for herself, then what about for Meghann or for Tristan, who are barely in their 40s? Wouldn’t they be on these drugs for another 40 years, or even longer? But Barb said she wasn’t worried—not at all. “The technology is so much better now.” If any problems come up, the scientists will find solutions.