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  • Older Americans Are About to Lose a Lot of Weight

    Older Americans Are About to Lose a Lot of Weight

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    Imagine an older man goes in to see his doctor. He’s 72 years old and moderately overweight: 5-foot-10, 190 pounds. His blood tests show high levels of triglycerides. Given his BMI—27.3—the man qualifies for taking semaglutide or tirzepatide, two of the wildly popular injectable drugs for diabetes and obesity that have produced dramatic weight loss in clinical trials. So he asks for a prescription, because his 50th college reunion is approaching and he’d like to get back to his freshman-year weight.

    He certainly could use these drugs to lose weight, says Thomas Wadden, a clinical psychologist and obesity researcher at the University of Pennsylvania, who recently laid out this hypothetical in an academic paper. But should he? And what about the tens of millions of Americans 65 and older who aren’t simply trying to slim down for a cocktail party, but live with diagnosable obesity? Should they be on Wegovy or Zepbound?

    Already, seniors make up 26.6 percent of the people who have been prescribed these and other GLP-1 agonists, including Ozempic, since 2018, according to a report from Truveta, which draws data from a large network of health-care systems. In the coming years, that proportion could rise even higher: The bipartisan Treat and Reduce Obesity Act, introduced in Congress last July, would allow Medicare to cover drug treatments for obesity among its roughly 50 million Part D enrollees above the age of 65; in principle, about two-fifths of that number would qualify as patients. Even if this law doesn’t pass (and it’s been introduced half a dozen times since 2012), America’s retirees will continue to be prescribed these drugs for diabetes in enormous numbers, and they’ll be losing weight on them as well. One way or another, the Boomers will be giving shape to our Ozempic Age.

    Economists say the cost to Medicare of giving new drugs for obesity to just a fraction of this aging generation would be staggering—$13.6 billion a year, according to an estimate published in The New England Journal of Medicine last March. But the health effects of such a program might also be unsettling. Until recently, the very notion of prescribing any form of weight loss whatsoever to an elderly patient—i.e., someone 65 or older—was considered suspect, even dangerous. “Advising weight loss in obese older adults is still shunned in the medical community,” the geriatric endocrinologist Dennis Villareal and his co-authors wrote in a 2013 “review of the controversy” for a medical journal. More than a decade later, clinicians are still struggling to reach consensus on safety, Villareal told me.

    Ample research shows that interventions for seniors with obesity can resolve associated complications. Wadden helped run a years-long, randomized trial of dramatic calorie reduction—using liquid meal replacements, in part—and stringent exercise advice for thousands of overweight adults with type 2 diabetes. “Clearly the people who were older did have benefits in terms of improved glycemic control and blood-pressure control,” he told me. Other, smaller studies led by Villareal find that older people who succeed at losing weight through diet and exercise end up feeling more robust.

    Such outcomes are significant on their own terms, says John Batsis, who treats and studies geriatric obesity at the UNC School of Medicine. “When we talk about older adults, we really need to be thinking about what’s important to older adults,” he told me. “It’s for them to be able to get on the floor and play with their grandchildren, or to be able to walk down the hallway without being completely exhausted.” But weight loss can also have adverse effects. When a person addresses their obesity through dieting alone, as much as 25 percent of the weight they lose derives from loss of muscle, bone, and other fat-free tissue. For seniors who, through natural aging, are already near the threshold of developing a functional impairment, a sudden drop like this could be enfeebling. Wadden’s trial found that, among the people who were on the weight-loss program for more than a decade, their risk of fracture to the hip, shoulder, upper arm, or pelvis increased by 39 percent. An analogous increase has turned up in studies of patients who undergo bariatric surgery, Batsis told me.

    Read: Ozempic makes you lose more than fat

    The effect of dieting on muscle and bone can be attenuated, but not prevented, through resistance training. And obesity itself—which is associated with higher bone density, but perhaps also reduced bone quality—may pose its own fracture risks, Batsis said. But even when a weight-loss treatment benefits an older patient, what happens when it ends? People tend to regain fat, but they don’t recover bone and muscle, Debra Waters, the director of gerontology research at the University of Otago, in New Zealand, told me. That makes the long-term effects of these interventions for older adults very murky. “What happens when they’re 80? Are they going to have really poor bone quality, and be at higher risk of fracture? We don’t know,” Waters said. “It’s a pretty big gamble to take, in my opinion.”

    Villareal told me that doctors should apply “the general principle of starting slow and going slow” when their older patients are trying to lose weight. But that approach doesn’t necessarily square with the rapid and remarkable weight loss seen in patients who are taking semaglutide or tirzepatide, which may produce a greater proportional loss of muscle and bone. (For semaglutide, it appears to be about 40 percent.)

    Then again, when given to laboratory animals, GLP-1 drugs seem to tamp down inflammation in the brain; and they’re now in clinical trials to see whether they might slow the progression of Alzheimer’s disease and dementia. Their multiple established benefits could also help seniors address several chronic problems—diabetes, obesity, fatty liver disease, and kidney disease, for instance—all at once. “Such a ‘one-stop shop’ approach can lead to reduction of medication burden, adverse drug events, hypoglycemic episodes, medication costs, and treatment nonadherence,” one team of geriatricians proposed in 2019.

    Overall, Batsis remains optimistic. “As a clinician, I’m very excited about these medications,” he told me. As a scientist, though, he’s inclined to wait and see. It’s surely true that some degree of weight loss is a great idea for some older patients. “But the million-dollar question is: What’s the sweet spot? How much weight is really enough? Is it 5 to 10 percent? Or is it 25 percent? We don’t know.” Waters said that if Medicare is going to pay for people’s Wegovy, then it should also cover scans of their body composition, to help predict how weight loss might affect their muscles and bones. Wadden said he thinks that treatments should be limited to people who have specific, weight-related complications. For everyone else—as for the hypothetical 72-year-old man who is prepping for his college reunion—he counsels prudence.

    To some extent, such advice is beside the point. Older people are already on Ozempic, and they’re already on Trulicity, and some of them are already taking GLP-1 drugs as a treatment for obesity. Truveta reported that the patients in its member health-care systems who are over 65 have received 281,000 prescriptions for GLP-1 drugs across the past five years. Given the network’s size, one can assume that at least 1 million seniors, overall, have already tried these medications. Millions more will try them in the years to come. If we still have questions about their use, mass experience will start providing answers.

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    Daniel Engber

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  • BMI Won’t Die

    BMI Won’t Die

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    If anything defines America’s current obesity-drug boom, it’s this: Many more people want these injections than can actually get them. The roadblocks include exorbitant costs that can stretch beyond $1,000 a month, limited insurance coverage, and constant supply shortages. But before all of those issues come into play, anyone attempting to get a prescription will inevitably confront the same obstacle: their body mass index, or BMI.

    So much depends on the simple calculation of dividing one’s weight by the square of their height. According to the FDA, people qualify for prescriptions of Wegovy and Zepbound—the obesity-drug versions of the diabetes medications Ozempic and Mounjaro—only if their BMI is 3o or higher, or 27 or higher with a weight-related health issue such as hypertension. Many who do get on the medication use BMI to track their progress. That BMI is the single biggest factor determining who gets prescribed these drugs, and who doesn’t, is the result of how deeply entrenched this metric has become in how both doctors and regular people approach health: Low BMI is good and high BMI is bad, or so most of us have come to think.

    This roughly 200-year-old metric has never been more relevant—or maligned—than it is in the obesity-drug era. BMI has become like the decrepit car you keep driving because it still sort of works and is too much of a hassle to replace. Its numerous shortcomings have been called out for many years now: For starters, it accounts for only height and weight, not other, more pertinent measures such as body-fat percentage. In June, the American Medical Association formally recognized that BMI should not be used alone as a health measure. Last year, some doctors called for BMI to be retired altogether, echoing previous assertions.

    The thing is, BMI can be an insightful health metric, but only when used judiciously with other factors. The problem is that it often hasn’t been. Just as obesity drugs are taking off, however, professional views are changing. People are so accustomed to seeing BMI as the “be-all, end-all” of health indicators, Kate Bauer, a nutritional-sciences professor at the University of Michigan, told me. “But that’s increasingly not the way it’s being used in clinical practice.” A shift in the medical field is a good start, but the bigger challenge will be getting everyone else to catch up.

    BMI got its start in the 1830s, when a Belgian astronomer named Adolphe Quetelet attempted to determine the properties of the “average” man. Using data on primarily white people, he observed that weight tended to vary as the square of height—a calculation that came to be known as Quetelet’s index.

    Over the next 150 years, what began as a descriptive tool transformed into a prescriptive one. Quetelet’s index (and other metrics like it) informed height-weight tables used by life-insurance companies to estimate risk. These sorts of tables formed “recommendations for the general population going from ‘average’ to ‘ideal’ weights,” the epidemiologist Katherine Flegal wrote in her history of BMI; eventually, nonideal weights were classified as “overweight” and “obese.” In 1972, the American physiologist Ancel Keys proposed using Quetelet’s index—which he renamed BMI—to roughly measure obesity. We’ve been stuck with BMI ever since. The metric became embedded not only in research and doctor’s visits but also in the very definitions of obesity. According to the World Health Organization, a BMI starting at 25 and less than 30 is considered overweight; anything above that range is obese.

    But using BMI to categorize a person’s health was controversial from the start. Even Keys called it “scientifically indefensible” to use BMI to judge someone as overweight. BMI doesn’t account for where fat is distributed on the body; fat that builds up around organs and tissues, called visceral fat, is linked to serious medical issues, while fat under the skin—the kind you can pinch—is usually less of a problem. Muscularity is also overlooked: LeBron James, for example, would be considered overweight. Both fat distribution and muscularity can vary widely across sex, age, and ethnicity. People with high BMIs can be perfectly healthy, and “there are people with normal BMIs that are actually sick because they have too much body fat,” Angela Fitch, an assistant professor at Harvard Medical School and the president of the Obesity Medicine Association, told me.

    For all its flaws, BMI is actually useful at the population level, Fitch said, and doctors can measure it quickly and cheaply. But BMI becomes troubling when it is all that doctors see. In some cases, the moment when a patient’s BMI is calculated by their doctor may shape the rest of the appointment and relationship going forward. “The default is to hyper-focus on the weight number, and I just don’t think that that’s helpful,” Tracy Richmond, a pediatrics professor at Harvard Medical School, told me. Anti-obesity bias is well documented among physicians—even some obesity specialists—and can lead them to dismiss the legitimate medical needs of people with a high BMI. In one tragic example, a patient died from cancer that went undiagnosed because her doctors attributed her health issues to her high BMI.

    But after many decades, the medical community has begun to use BMI in a different way. “More and more clinicians are realizing that there are people who can be quite healthy with a high BMI,” Kate Bauer said. The shift has been gradual, though it was given a boost by the AMA policy update earlier this year: “Hopefully that will help clinicians make a change to supplement BMI with other measures,” Aayush Visaria, an internal-medicine resident at Rutgers Robert Wood Johnson Medical School who researches BMI’s shortcomings, told me.

    Physicians I spoke with acknowledged BMI’s flaws but didn’t seem too concerned about its continued use in medicine—even as obesity drugs make this metric even more consequential. BMI isn’t a problem, they said, as long as physicians consider other factors when diagnosing obesity or prescribing drugs to treat it. If you go to a doctor with the intention of getting on an obesity drug, you should be subject to a comprehensive evaluation including metrics such as blood sugar, cholesterol levels, and body composition that go “way beyond BMI,” Katherine Saunders, a clinical-medicine professor at Weill Cornell Medicine, said. Because Wegovy and other drugs come with side effects, she told me, doctors must be absolutely sure that a patient actually needs them, she added.

    But BMI isn’t like most other health metrics. Because of its simplicity, it has seeped out of doctor’s offices and into the mainstream, where this more nuanced view still isn’t common. Whether we realize it or not, BMI is central to our basic idea of health, affecting nearly every aspect of daily life. Insurance companies are notorious for charging higher rates to people with high BMI and lowering premiums for people who commit to long-term weight loss. Fertility treatments and orthopedic and gender-affirming surgery can be withheld from patients until they hit BMI targets. Workplace wellness programs based on BMI are designed to help employees manage their weight. BMI has even been used to prevent prospective parents from adopting a child.

    The rise of obesity drugs may make these kinds of usages of BMI even harder to shake. Determining drug eligibility by high BMI supports the notion that a number is synonymous with illness. Certainly many people using obesity drugs take a holistic view of their health, as doctors are learning to do. But focusing on BMI is still common. Some members of the r/Ozempic Subreddit, for example, share their BMI to show their progress on the drug. Again, high BMI can be used to predict who has obesity, but it isn’t itself an obesity diagnosis. The problem with BMI’s continued dominance is that it makes it even harder to move away from simply associating a number on a scale with overall health, with all the downstream consequences that come along with a weight-obsessed culture. As obesity drugs are becoming mainstream, “there needs to be public education explaining that BMI by itself may not be a good indicator of health,” Visaria said.

    In another 200 years, surely BMI will finally be supplanted by something else. If not much sooner: A large effort to establish hard biological criteria for obesity is under way; the goal is to eliminate BMI-based definitions once and for all. Caroline Apovian, a professor at Harvard Medical School, gives it “at least 10 years” before a comparably cheap or convenient replacement arises—though any changes would take longer to filter into public consciousness.” Until that happens, we’re stuck with BMI, and the mess it has wrought.

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    Yasmin Tayag

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  • It’s the Best Time in History to Have a Migraine

    It’s the Best Time in History to Have a Migraine

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    Here is a straightforward, clinical description of a migraine: intense throbbing headache, nausea, vomiting, and sensitivity to light and noise, lasting for hours or days.

    And here is a fuller, more honest picture: an intense, throbbing sense of annoyance as the pain around my eye blooms. Wondering what the trigger was this time. Popping my beloved Excedrin—a combination of acetaminophen, aspirin, and caffeine—and hoping it has a chance to percolate in my system before I start vomiting. There’s the drawing of the curtains, the curling up in bed, the dash to the toilet to puke my guts out. I am not a religious person, but during my worst migraines, I have whimpered at the universe, my hands jammed into the side of my skull, and begged it for relief.

    That probably sounds melodramatic, but listen: Migraines are miserable. They’re miserable for about 40 million Americans, most of them women, though the precise symptoms and their severity vary across sufferers. For about a quarter, myself included, the onset is sometimes preceded by an aura, a short-lived phase that can include blind spots, tingling, numbness, and language problems. (These can resemble stroke symptoms, and you should seek immediate medical care if you experience them and don’t have a history of migraines.) Many experience a final phase known as the “migraine hangover,” which consists of fatigue, trouble concentrating, and dizziness after the worst pain has passed.

    These days, migraine sufferers are caught in a bit of a paradox. In some ways, their situation looks bright (but, please, not too bright): More treatments are available now than ever before—though still no cure—and researchers are learning more about what triggers a migraine, with occasionally surprising results. “It’s a really exciting time in headache medicine,” Mia Minen, a neurologist and the chief of headache research at NYU Langone, told me.

    And yet the enthusiasm within the medical community doesn’t seem to align with conditions on the ground (which, by the way, is a nice, cool place to press your cheek during an attack). Migraine sufferers cancel plans and feel guilty about it. They struggle to parent. They call in sick, and if they can’t, they move through the work day like zombies. In a 2019 survey, about 30 percent of participants with episodic migraines—attacks that occur on fewer than 15 days a month—said that the disorder had negatively affected their careers. About 58 percent with chronic migraines—attacks that occur more often than that—said the same.

    Migraines are still misunderstood, including by the people who deal with them. “We still don’t have a full understanding of exactly what causes migraine, and why some people suffer more than others do,” Elizabeth Loder, a headache clinician at Brigham and Women’s Hospital in Boston and a neurology professor at Harvard Medical School, told me. Despite scientific progress, awareness campaigns, and frequent reminders that migraines are a neurological disorder and not “just headaches,” too often, they’re not treated with the medical care they require. Yes, it’s the best time in history to have migraines. It just doesn’t feel that way.

    Humans have had migraines probably for as long as we’ve had brains. As the historian Katherine Foxhall argues in her 2019 book, Migraine: A History, “much evidence suggests migraine had been taken seriously in both medical and lay literature throughout the classical, medieval, and early modern periods as a serious disorder requiring prompt and sustained treatment.” It was only in the 18th century, when medical professionals lumped migraines in with other “nervous disorders” such as hysteria, that they “came to be seen as characteristic of sensitivity, femininity, overwork, and moral and personal failure.” The association persisted, Stephen Silberstein, the director of the headache center at Thomas Jefferson University, told me. When Silberstein began his training in the 1960s, “nobody talked about migraine in medical school,” he told me. Physicians still believed that migraines were “the disorder of neurotic women.”

    The first drug treatments for migraines appeared in the 1920s, and they were discovered somewhat by accident: Doctors found that ergotamine, a drug used to stimulate contractions in childbirth and control postpartum bleeding, also sometimes relieved migraines. (It could also cause pain, muscle weakness, and, in high enough doses, gangrene; some later studies have found that it’s little better than placebo.) The drug constricted blood vessels in the brain, so doctors assumed that migraine was a vascular disorder, the symptoms brought on by changes in blood flow and inflamed vessels. In the 1960s, a physician studying the effectiveness of a heart medication noticed that one of his participants experienced migraine attacks less frequently than he used to; a decade later, the FDA approved that class of drug, called beta-blockers, as a preventative treatment. (In the decades since their approval, studies have found that beta-blockers helped about a quarter of participants reduce their monthly migraine days by half, compared with 4 percent of people taking a placebo.)

    Things changed in the 1990s, when triptans, a new class of drugs made specifically for migraines, became available. Triptans were often more effective and faster at easing migraine pain than earlier drugs, though the effects didn’t last as long. Around the same time, genetic studies revealed that migraines are often hereditary. Meanwhile, new brain-imaging technology allowed researchers to observe migraines in real time. It showed that, although blood vessels could become inflamed during an attack and contribute to pain, migraine isn’t strictly a vascular disorder. The chaos comes from within the nervous system: Scientists’ best understanding is that the trigeminal nerve, which provides sensation in the face, becomes stimulated, which triggers cells in the brain to release neurotransmitters that produce headache pain. How exactly the nerve gets perturbed remains unclear.

    Read: Doctors suddenly got way better at treating eczema

    The past few years of migraine medicine have felt like the ’90s all over again. In 2018, the FDA approved a monthly injection that prevents migraines by regulating CGRP, a neurotransmitter that’s known to spike during attacks. For 40 percent of people with chronic migraines participating in one clinical trial, the treatment cut their monthly migraine days in half. Similar remedies followed; Lady Gaga, a longtime migraine sufferer, appeared in a commercial this summer to endorse Pfizer’s CGRP-blocking pill, and the company’s CEO launched a migraine-awareness campaign earlier this month. Solid evidence has emerged that cognitive behavioral therapy and relaxation techniques tailored to migraine can be helpful as part of a larger treatment plan. The FDA has cleared several wearable devices designed to curb migraines by delivering mild electric stimulation. Last year, the agency decided to speed up the development of a device that deploys gentle puffs of air into a user’s ears.

    Researchers are still, to this day, making progress on identifying migraine triggers. Experts agree on many common triggers, such as skipping meals, getting too little sleep, getting too much sleep, stress, the comedown from stress, and hormone changes linked to menstruation or menopause. They’re also realizing that some long-held beliefs about triggers might be entirely wrong. MSG, for example, probably doesn’t induce migraines; changes in air pressure don’t do so as often as many people who have migraines seem to think.

    Some supposed triggers might actually be signs of an oncoming migraine. The majority of migraine sufferers experience something called the premonitory phase, which can last for several hours or days before headache pain sets in and has its own set of symptoms, including food cravings. We migraine sufferers are frequently advised to steer clear of chocolate, but if you’re craving a Snickers bar, the migraine may already be coming whether or not you eat it. “When you get a headache, you blame it on the chocolate—even though the migraine made you eat the chocolate,” Silberstein said. “I always tell people, if they think they’re getting a migraine, eat a bar of chocolate … It’s more likely to do good than harm.”

    Silberstein’s advice sounded like absolute blasphemy to me. Virtually every migraine FAQ page in existence had led me to believe that chocolate is a ruthless trigger. Maybe I shouldn’t have been relying on general guidelines on the internet, even though they came from reputable medical institutions. But I had turned to the internet because I didn’t think my migraines necessitated a visit to a specialist. According to the American Migraine Foundation, the majority of people who have migraines never consult a doctor to receive proper diagnosis and treatment.

    Recent surveys have shown that people are reluctant to see a professional for a variety of reasons: They think their migraine isn’t bad enough, they worry that their symptoms won’t be taken seriously, or they can’t afford the care. The hot new preventative medications in particular “are extremely expensive, putting them out of reach of some of the people who might benefit the most,” Loder said. In 2018, when the much-heralded CGRP blocker hit the market, the journalist Libby Watson, a longtime migraine patient herself, interviewed migraine sufferers who described themselves as low-income, and found that most of them hadn’t heard of the new drug at all.

    Even if you can get them, the treatments don’t guarantee relief. One recent study showed that triptans might not relieve pain—or might not be tolerable—for up to 40 percent of migraine patients. Experts are still trying to figure out why the same treatment might work wonderfully for one person, and not at all for another, Minen said. Some patients find that drugs eventually stop working for them, or that they come with side effects bad enough to discourage continued use, such as dizziness and still more nausea.

    Read: Why has a useless cold medication been allowed on shelves for years?

    These problems remain unsolved in part because of a dearth of research. Like other conditions that mostly afflict women, migraines receive “much less funding in proportion to the burden they exert on the U.S. population,” Nature’s Kerri Smith reported in May. And many doctors are unaware of the research that exists: A 2021 study of non-migraine physicians found that 43 percent had “poor knowledge” of the condition’s symptoms and management, and just 21 percent were aware of targeted treatments. Specialists tend to have a much better knowledge base, but good luck seeing one: America has too few headache doctors, and there are significantly fewer of them in rural areas.

    Many migraine sufferers rely on over-the-counter pain relievers, myself included. Years ago, my primary-care physician prescribed me a triptan nasal spray. It produced a terrible aftertaste and worsened the throbbing in my head, and I gave up on it after only a couple of uses. Back to Excedrin I went, not realizing—until reporting this story—that nonprescription medications can cause even more attacks if you overuse them. Some people get by on home remedies that the journalist Katy Schneider, who battles migraines herself, has described as a “medicine cabinet of curiosities”; one person she interviewed shotguns an ice-cold Coke when she feels the symptoms coming on.

    When triptans and tricks fail, some people try to prevent migraines by avoiding triggers. Don’t stay up too late or sleep in. Don’t drink red wine. Put down that Snickers. This strategy of avoidance “interferes with the quality of their life in many cases,” Loder said, and probably doesn’t stop the attacks. And drawing associations is a futile exercise because most migraines are brought on by more than one trigger, Minen said. People can end up internalizing the 18th-century idea that migraines are a personal failure rather than a disease—and migraine FAQs perpetuate that myth by advising patients to live an ascetic life.

    Read: Adult ADHD is the Wild West of psychiatry

    The misconceptions surrounding migraine, combined with its invisibility, make the disorder easy to stigmatize. The authors of a 2021 review found that, compared with epilepsy, a neurological disorder with a physical manifestation, “people with chronic migraine are viewed as less trustworthy, less likely to try their hardest, and more likely to malinger.” Perhaps as a result, many feel pressure to grind through it. Migraines are estimated to account for 16 percent of presenteeism—being on the job but not operating at full capacity—in the American workforce.

    Before reporting this story, I had never thought to call my migraines a neurological disorder, let alone a “debilitating” one, as Minen and other experts do. Migraines were just this thing that I’ve lived with for more than a decade, and had accepted as an unfortunate part of my existence. Just my Excedrin and me, together forever, barreling through the wasted days. The attacks began in my late teens, around the same time that my childhood epilepsy mysteriously vanished. I never got an explanation for my seizures, despite years of daily medication and countless EEGs. A neurologist once told me that the two might be related, but he couldn’t say for sure; research has shown that people who have epilepsy are more likely to experience migraines. And so I assumed that I just had a slightly broken brain, prone to electrochemical misfiring.

    All of the experts I spoke with were politely horrified when I told them about my migraines and how I manage them. I promised them that I’d make an appointment with a specialist. Before we got off the phone, Silberstein gave me a tip. “Put a cold pack on your neck and then a heating pad, 15 minutes alternating,” he said. “It’ll take the migraine away.” He told me that researchers are developing a device that does this, but the old-fashioned way can be effective too. At this point, my cabinet of curiosities is falling apart, its hinges squeaking from overuse. I’m already rethinking my entire migraine life, so I may as well try this too.

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    Marina Koren

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  • We’ve Had a Cheaper, More Potent Ozempic Alternative for Decades

    We’ve Had a Cheaper, More Potent Ozempic Alternative for Decades

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    The Ozempic craze shows no signs of slowing. Demand for the drug, popularly used for weight loss, is so monumental that it is already changing the diet industry and spurring a “marketing bonanza” among the dozens of telehealth start-ups that now prescribe it. A highly public ad campaign from one start-up, Ro, banks on the drug’s simple premise: “A weekly shot to lose weight.”

    Never before has a weight-loss treatment been hyped this way and been able to deliver on its promise. Ozempic itself is technically a diabetes drug, but its active ingredient, semaglutide, has been approved by the FDA for weight loss under the brand name Wegovy, and can reduce a person’s body weight by up to 20 percent through a weekly injection. An even more powerful drug, known as tirzepatide, or Mounjaro, may soon be approved for weight loss, and a host of new medications are coming down the pipeline. All signs suggest that America is on the verge of a weight-loss revolution.

    But for people with obesity, semaglutide isn’t even the most effective weight-loss treatment around—not even close. Bariatric surgery, which has existed for many decades, is still significantly more potent. This class of procedures, which, broadly speaking, reconfigure the digestive system so people feel less hungry and more full, is considered to be the “gold standard” for treating obesity, Holly Lofton, an obesity-medicine physician at NYU, told me. Most people experience weight loss of 50 percent and, with one procedure, up to 80 percent, according to the Cleveland Clinic.

    Despite the impressive abilities of the new crop of weight-loss drugs—and bold assertions that such drugs could someday replace surgery outright—several doctors told me that surgery will likely continue to be the top-line treatment for obesity, even as the medications improve. People may seek out treatment with the new drugs because they’re so popular, but “long term, there will be an increase in surgery,” Shauna Levy, a professor specializing in bariatric surgery at Tulane University School of Medicine, told me. The new drugs, however potent, may be less a revolutionary fix for obesity and more a powerful tool for treating it—one of many that already exist.

    Unlike semaglutide, bariatric surgery, first introduced in the 1950s, took several decades to become accepted by the medical community. Initial attempts made people so sick that, at times, the surgery had to be reversed. The term bariatric surgery refers to several different procedures that reshape the gastrointestinal tract so that it absorbs fewer nutrients, holds less food, or both. These days, the most commonly performed surgery is called a Roux-en-Y, which shrinks the stomach to the size of a walnut—so people need less food to feel satisfied—and then reconnects it to the small intestine in a Y shape, rather than linearly. This gastric bypass lets food circumvent most of the stomach, leaving fewer opportunities for the body to harvest nutrients. In another common procedure, surgeons sculpt the stomach into a banana-size “sleeve” and toss the rest; another common type involves rerouting the intestines in a way that minimizes the area where calories can be absorbed.

    But bariatric surgery does more than shrink gastrointestinal real estate. It exerts a less visible but equally powerful effect on the many different hormones that control hunger. Some procedures remove the part of the gut that produces the “hunger hormone,” ghrelin, while the rerouting of food through a Roux-en-Y ramps up the release of “incretin” hormones that create the feeling of fullness after eating.

    In a sense, the new weight-loss drugs are essentially trying to re-create the effects of bariatric surgery: The success of these drugs is due to their ability to mimic the incretin hormones and get people to feel satisfied with less food. Semaglutide masquerades as the hormone GLP-1, whereas Mounjaro poses as both GLP-1 and GIP. But these are just two hormones; bariatric surgery “touches on multiple different hormones and different pathways” and, as such, is “more comprehensive,” Levy said. In one study, Mounjaro, considered the most powerful of the current crop of medications, led to 20 percent or more weight loss in 57 percent of people who took the highest dose—an impressive feat, but still a far cry from what is possible with surgery. Similarly, Ozempic and Mounjaro, both technically diabetes drugs, have powerful effects on blood-sugar levels over time, but many surgery patients “leave the hospital already in remission from their diabetes,” Levy said.

    In addition to sheer potency, surgery is also much more affordable than these weight-loss drugs. Unlike the drugs, bariatric surgery is covered by Medicare if the patient meets certain criteria, including having a BMI equal to or greater than 35 and at least one comorbidity related to obesity. Many private insurers cover it too, albeit to varying degrees. Out of pocket, surgery costs $15,000 to $25,000—not cheap, but still cheaper than shelling out more than $1,000 a month indefinitely. “The patient must understand that they have to continue taking medication forever,” Lofton said. People who stop taking semaglutide generally regain the weight they lost. Lofton told me about one patient who had to forgo rent just to pay for the drugs: Factoring in insurance, “you can pay for three months of medicine and then have surgery at the same price.”

    Neither treatment, of course, is without its potential downsides. Semaglutide can cause temporary but nasty side effects such as nausea, vomiting, and diarrhea—and though it is considered safe for treating obesity, long-term data on this usage span just two years. Because many surgeries are done laparoscopically—using only tiny incisions—mortality is vanishingly low, and many patients go home after two or three days; full recovery usually takes four to six weeks. In the long term, complications such as hernias, gallstones, and low blood sugar can develop.

    But there’s a reason bariatric surgery has not led to a weight-loss revolution of the kind that now gets associated with semaglutide. Despite its dramatic effects, and obesity’s prevalence across America, only 1 percent of people eligible for surgery actually get it. People hesitate for many reasons, medical and otherwise, but the most pervasive issue is a lack of awareness that surgery is even a safe or realistic option for weight loss. Bariatric surgery is plagued by stigma even within the medical community: In the 1990s, it was dismissed as a “barbaric” way to address an issue that, many believed, could be treated with diet and exercise. “There are a lot of primary-care doctors who are not talking enough about surgery” because they were trained with that old mindset, Levy said. ​​It doesn’t help that bariatric surgery hasn’t exactly been a media sensation, with few high-profile patient advocates beyond Al Roker and Mariah Carey. In contrast, stories of celebrities on weight-loss drugs abound. Unlike surgery, semaglutide has the potential to be taken recreationally.

    The advantages that surgery has over weight-loss drugs may change as the drugs become more potent and eventually cheaper. But for now, semaglutide won’t dramatically shift the way obesity is treated, doctors told me—in fact, these new drugs may act as a conduit to surgery itself. Levy predicts that their sheer popularity will trigger a brief dip in the bariatric-surgery rate, but as price remains an issue, and people with obesity are unable to reach their weight-loss goals on the drugs alone, “they may start opening their mind to surgery.”

    Certainly, in some patients, weight-loss drugs alone could lead to lasting weight loss. And they can benefit those who are overweight but don’t qualify for surgery. But more widely, these drugs will likely be used in tandem with bariatric surgery to produce more dramatic, longer-lasting results, experts told me. “I don’t see this as an either/or,” Fatima Cody Stanford, an obesity-medicine physician at Massachusetts General Hospital and Harvard Medical School, told me. “I see it as surgery plus medicine.”

    Drugs can help fill in any gaps that surgery leaves behind. Weight can rebound after a procedure, because the body has a way of rebalancing itself; hormones that were tamped down due to bariatric surgery, Stanford said, can “start to reemerge with a vengeance.” About a fifth of people, and perhaps even more, regain a significant amount of weight—15 percent or more—two to five years after surgery. All of the doctors I spoke with said that medication could be a powerful tool to prevent post-surgery weight rebounds—though to keep that weight off, the medication would still have to be taken in perpetuity. Stanford estimated that more than 90 percent of her patients are on weight-loss drugs after surgery—and not necessarily semaglutide; older medications often suffice. Drugs could also be used to help people prepare for surgery, Lofton said. Some doctors encourage patients to lose weight beforehand to decrease the risk of complications such as blood clots, heart attack, and infection.

    Despite the hype, weight-loss drugs were never a perfect treatment for obesity. Neither is bariatric surgery, for that matter. “It is not a cure,” Lofton told me. A cure, she explained, would ensure that hunger doesn’t return and that fat cells don’t get bigger, a hallmark of obesity: “We have nothing that does that”—not even more potent next-gen drugs will provide a permanent fix. But the effect of combining surgery and medication could come close, she said.

    That no cure for obesity exists is evidence of its complexity. All of the experts I spoke with pointed out that obesity has long been misunderstood as a failure of personal will, as laziness or gluttony. That misunderstanding has led to inadequate care: Many people who regain weight after a bariatric procedure are made to feel by their doctors like they “wasted the surgery,” even if human biology is to blame, Stanford said. Ozempic and other weight-loss medications frame obesity as a condition that can be treated with drugs—in other words, a disease. Patients on those medications may realize, “Hey, maybe it’s not just me being lazy this whole time—maybe there is science to it and an actual disease here,” said Levy. Collectively understanding obesity as an illness that exists alongside heart disease and cancer—diseases routinely treated with medication and surgery—instead of as a matter of personal inadequacy will have far more profound impacts on people with obesity than any drug alone.

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    Yasmin Tayag

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  • Long COVID Has Forced a Reckoning for One of Medicine’s Most Neglected Diseases

    Long COVID Has Forced a Reckoning for One of Medicine’s Most Neglected Diseases

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    Kira Stoops lives in Bozeman, Montana—a beautiful mountain town where it sometimes feels like everyone regularly goes on 50-mile runs. Stoops, however, can’t walk around her own block on most days. To stand for more than a few minutes, she needs a wheeled walker. She reacts so badly to most foods that her diet consists of just 12 ingredients. Her “brain fog” usually lifts for a mere two hours in the morning, during which she can sometimes work or, more rarely, see friends. Stoops has myalgic encephalomyelitis, or chronic fatigue syndrome (ME/CFS). “I’m considered a moderate patient on the mild side,” she told me.

    ME/CFS involves a panoply of debilitating symptoms that affect many organ systems and that get worse with exertion. The Institute of Medicine estimates that it affects 836,000 to 2.5 million people in the U.S. alone, but is so misunderstood and stigmatized that about 90 percent of people who have it have never been diagnosed. At best, most medical professionals know nothing about ME/CFS; at worst, they tell patients that their symptoms are psychosomatic, anxiety-induced, or simply signs of laziness. While ME/CFS patients, their caregivers, and the few doctors who treat them have spent years fighting for medical legitimacy, the coronavirus pandemic has now forced the issue.

    A wide variety of infections can cause ME/CFS, and SARS-CoV-2, the coronavirus that causes COVID-19, is no different: Many cases of long COVID are effectively ME/CFS by another name. The exact number is hard to define, but past studies have shown that 5 to 27 percent of people infected by various pathogens, including Epstein-Barr virus and the original SARS, develop ME/CFS. Even if that proportion is 10 times lower for SARS-CoV-2, the number of Americans with ME/CFS would still have doubled in the past three years. “We’re adding an immense volume of patients to an already dysfunctional and overburdened system,” Beth Pollack, a scientist at MIT who studies complex chronic illnesses, told me.

    The U.S. has so few doctors who truly understand the disease and know how to treat it that when they convened in 2018 to create a formal coalition, there were only about a dozen, and the youngest was 60. Currently, the coalition’s website lists just 21 names, of whom at least three have retired and one is dead, Linda Tannenbaum, the CEO and president of the Open Medicine Foundation, told me. These specialists are concentrated on the coasts; none work in the Midwest. American ME/CFS patients may outnumber the population of 15 individual states, but ME/CFS specialists couldn’t fill a Major League Baseball roster. Stoops, who is 39, was formally diagnosed with ME/CFS only four years ago, and began receiving proper care from two of those specialists—Lucinda Bateman of the Bateman Horne Center and David Kaufman from the Center for Complex Diseases. Bateman told me that even before the pandemic, she could see fewer than 10 percent of the patients who asked for a consultation. “When I got into those practices, it was like I got into Harvard,” Stoops told me.

    ME/CFS specialists, already overwhelmed with demand for their services, now have to decide how to best use and spread their knowledge, at a time when more patients and doctors than ever could benefit from it. Kaufman recently discharged many of the more stable ME/CFS patients in his care—Stoops among them—so that he could start seeing COVID long-haulers who “were just making the circuit of doctors and getting nowhere,” he told me. “I can’t clone myself, and this was the only other way to” make room for new patients.

    Bateman, meanwhile, is feverishly focused on educating other clinicians. The hallmark symptom of ME/CFS—post-exertional malaise, or PEM—means even light physical or mental exertion can trigger major crashes that exacerbate every other symptom. Doctors who are unfamiliar with PEM, including many now running long-COVID clinics, can unwittingly hurt their patients by encouraging them to exercise. Bateman is racing to spread that message, and better ways of treating patients, but that means she’ll have to reduce her clinic hours.

    These agonizing decisions mean that many existing ME/CFS patients are losing access to the best care they had found so far—what for Stoops meant “the difference between being stuck at home, miserable and in pain, and actually going out once or twice a day, seeing other humans, and breathing fresh air,” she told me. But painful trade-offs might be necessary to finally drag American medicine to a place where it can treat these kinds of complex, oft-neglected conditions. Kaufman is 75 and Bateman is 64. Although both of them told me they’re not retiring anytime soon, they also won’t be practicing forever. To make full use of their expertise and create more doctors like them, the medical profession must face up to decades spent dismissing illnesses such as ME/CFS—an overdue reckoning incited by long COVID. “It’s a disaster possibly wrapped up in a blessing,” Stoops told me. “The system is cracking and needs to crack.”

    Many ME/CFS specialists have a deep knowledge of the disease because they’ve experienced it firsthand. Jennifer Curtin, one of the youngest doctors in the field, has two family members with the disease, and had it herself for nine years. She improved enough to make it through medical school and residency training, which showed her that ME/CFS “just isn’t taught,” she told me. Most curricula don’t include it; most textbooks don’t mention it.

    Even if doctors learn about ME/CFS, America’s health-care system makes it almost impossible for them to actually help patients. The insurance model pushes physicians toward shorter visits; 15 minutes might feel luxurious. “My average visit length is an hour, which doesn’t include the time I spend going over the patient’s 500 to 1,700 pages of records beforehand,” Curtin said. “It’s not a very scalable kind of care.” (She works with Kaufman at the Center for Complex Diseases, which bills patients directly.) This also explains why the cohort of ME/CFS clinicians is aging out, with little young blood to refresh them. “Hospital systems want physicians to see lots of patients and they want them to follow the rules,” Kaufman said. “There’s less motivation for moving into areas of medicine that are more unknown and challenging.”

    ME/CFS is certainly challenging, not least because it’s just “one face of a many-sided problem,” Jaime Seltzer, the director of scientific and medical outreach at the advocacy group MEAction, told me. The condition’s root causes can also lead to several distinct but interlocking illnesses, including mast cell activation syndrome, Ehlers-Danlos syndrome, fibromyalgia, dysautonomia (usually manifesting as POTS), and several autoimmune and gastrointestinal disorders. “I’m still amazed at how often patients come in with Complaint No. 1, and then I find five to seven of the other things,” Kaufman said. These syndromes collectively afflict many organ systems, which can baffle doctors who’ve specialized in just one. Many of them disproportionately affect women, and are subject to medicine’s long-standing tendency to minimize or psychologize women’s pain, Pollack told me: An average woman with Ehlers-Danlos syndrome typically spends 16 years getting a diagnosis, while a man needs only four.

    People with long COVID might have many of these conditions and not know about any—because their doctors don’t either. Like ME/CFS, they rarely feature in medical training, and it’s hard to “teach someone about all of them when they’ve never heard of any of them,” Seltzer said. Specialists like Bateman and Kaufman matter because they understand not just ME/CFS but also the connected puzzle pieces. They can look at a patient’s full array of symptoms and prioritize the ones that are most urgent or foundational. They know how to test for conditions that can be invisible to standard medical techniques: “None of my tests came back abnormal until I saw an ME/CFS doctor, and then all my tests came back abnormal,” said Hannah Davis of the Patient-Led Research Collaborative, who has had long COVID since March 2020.

    ME/CFS specialists also know how to help, in ways that are directly applicable to cases of long COVID with overlapping symptoms. ME/CFS has no cure but can be managed, often through “simple, inexpensive interventions that can be done through primary care,” Bateman told me. Over-the-counter antihistamines can help patients with inflammatory problems such as mast cell activation syndrome. Low doses of naltrexone, commonly used for addiction disorders, can help those with intense pain. A simple but rarely administered test can show if patients have orthostatic intolerance—a blood-flow problem that worsens other symptoms when people stand or sit upright. Most important, teaching patients about pacing—carefully sensing and managing your energy levels—can prevent debilitating crashes. “We don’t go to an ME/CFS clinic and walk out in remission,” Stoops told me. “You go to become stabilized. The ship has 1,000 holes, and doctors can patch one before the next explodes, keeping the whole thing afloat.”

    That’s why the prospect of losing specialists is so galling. Stoops understands why her doctors might choose to focus on education or newly diagnosed COVID long-haulers, but ME/CFS patients are “just so lost already, and to lose what little we have is a really big deal,” she said. Kaufman has offered to refer her to generalist physicians or talk to primary-care doctors on her behalf. But it won’t be the same: “Having one appointment with him is like six to eight appointments with other practitioners,” she said. He educates her about ME/CFS; with other doctors, it’s often the other way round. “I’m going to have to work much harder to receive a similar level of care.”

    At least, she will for now. The ME/CFS specialists who are shifting their focus are hoping that they can use this moment of crisis to create more resources for everyone with these diseases. In a few years, Bateman hopes, “there will be 100 times more clinicians who are prepared to manage patients, and many more people with ME/CFS who have access to care.”

    For someone who is diagnosed with ME/CFS today, the landscape already looks very different than it did just a decade ago. In 2015, the Institute of Medicine published a landmark report redefining the diagnostic criteria for the disease. In 2017, the CDC stopped recommending exercise therapy as a treatment. In 2021, Bateman and 20 other clinicians published a comprehensive guide to the condition in the journal of the Mayo Clinic. For any mainstream disease, such events—a report, a guideline revision, a review article—would be mundane. For ME/CFS, they felt momentous. And yet, “the current state of things is simply intolerable,” Julie Rehmeyer, a journalist with ME/CFS, told me. Solving the gargantuan challenge posed by complex chronic diseases demands seismic shifts in research funding, medical training, and public attitudes. “Achieving shifts like that takes something big,” Rehmeyer said. “Long COVID is big.”

    COVID long-haulers have proved beyond any reasonable doubt that acute viral infections can leave people chronically ill. Many health-care workers, political-decision makers, and influencers either know someone with long COVID or have it themselves. Even if they still don’t know about ME/CFS, their heightened awareness of post-viral illnesses is already making a difference. Mary Dimmock’s son developed ME/CFS in 2011, and before the pandemic, one doctor in 10 might take him seriously. “Now it’s the flip: Only one doctor out of 10 will be a real jerk,” Dimmock told me. “I attribute that to long COVID.”

    But being believed is the very least that ME/CFS patients deserve. They need therapeutics that target the root causes of the disease, which will require a clear understanding of those causes, which will require coordinated, well-funded research—three things ME/CFS has historically lacked. But here, too, “long COVID is going to be a catalyst,” Amy Proal, the president of the Polybio Research Foundation, told me. She is leading the Long Covid Research Initiative—a group of scientists, including ME/CFS researchers, that will use state-of-the-art techniques to see exactly how the new coronavirus causes long COVID, and rapidly push potential treatments through clinical trials. The National Institutes of Health has also committed $1.15 billion to long-COVID research, and while some advocates are concerned about how that money will be spent, Rehmeyer notes that the amount is still almost 80 times greater than the paltry $15 million spent on ME/CFS every year—less than any other disease in the NIH’s portfolio, relative to its societal burden. “Even if 90 percent is wasted, we’d be doing a lot better,” she said.

    While they wait for better treatments, patients also need the medical community to heed the lessons that they and their clinicians have learned. For example, the American Academy for Family Physicians website still wrongly recommends exercise therapy and links ME/CFS to childhood abuse. “That group of doctors is very important to these patients,” Dimmock said, “so what does that say to them about what this disease is all about?”

    Despite all evidence to the contrary, many clinicians and researchers still don’t see ME/CFS as a legitimate illness and are quick to dismiss any connection between it and long COVID. To ensure that both groups of patients get the best possible treatments, instead of advice that might harm them, ME/CFS specialists are working to disseminate their hard-won knowledge. Bateman and her colleagues have been creating educational resources for clinicians and patients, continuing-medical-education courses, and an online lecture series. Jennifer Curtin has spent two years mapping all the decisions she makes when seeing a new patient, and is converting those into a tool that other clinicians can use. As part of her new start-up, called RTHM, she’s also trying to develop better ways of testing for ME/CFS and its related syndromes, of visualizing the hefty electronic health records that chronically ill patients accumulate, and of tracking the treatments they try and their effects. “There are a lot of things that need to be fixed for this kind of care to be scalable,” Curtin told me.

    Had such shifts already occurred, the medical profession might have had more to offer COVID long-haulers beyond bewilderment and dismissal. But if the profession starts listening to the ME/CFS community now, it will stand the best chance of helping people being disabled by COVID, and of steeling itself against future epidemics. Pathogens have been chronically disabling people for the longest time, and more pandemics are inevitable. The current one could and should be the last whose long-haulers are greeted with disbelief.

    New centers that cater to ME/CFS patients are already emerging. RTHM is currently focused on COVID long-haulers but will take on some of David Kaufman’s former patients in November, and will open its waiting list to the broader ME/CFS community in December. (It is currently licensed to practice in just five states but expects to expand soon.) David Putrino, who leads a long-COVID rehabilitation clinic in Mount Sinai, is trying to raise funds for a new clinic that will treat both long COVID and ME/CFS. He credits ME/CFS patients with opening his eyes to the connection between long COVID and their condition.

    Every ME/CFS patient I’ve talked with predicted long COVID’s arrival well before most doctors or even epidemiologists started catching up. They know more about complex chronic illnesses than many of the people now treating long COVID do. Despite having a condition that saps their energy, many have spent the past few years helping long-haulers navigate what for them was well-trodden terrain: “I did barely anything but work in 2020,” Seltzer told me. Against the odds, they’ve survived. But the pandemic has created a catalytic opportunity for the odds to finally be tilted in their favor, “so that neither patients nor doctors of any complex chronic illness have to be heroes anymore,” Rehmeyer said.

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    Ed Yong

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