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Tag: bariatric surgery

  • Cartier Introduces New Diamond-Encrusted Gastric Lap-Band

    Cartier Introduces New Diamond-Encrusted Gastric Lap-Band

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    PARIS—Calling its latest piece a “must-have for anyone with a discerning eye” who is preparing to undergo bariatric surgery, the prestigious jewelry firm Cartier introduced a new diamond-encrusted gastric lap-band Friday retailing for $97,000. “The Maison Cartier is pleased to introduce a high-end implanted medical device for elegant consumers of taste and means who wish to add a bit of luxury to an upcoming weight-loss operation,” Cartier representative Angelique Moquin said as she pulled up an image from a helical CT scanner to show an adjustable white-gold gastric band paved with 3-carat brilliant-cut diamonds and tightened around the top portion of a jewelry model’s stomach. “No longer does reducing the capacity of your digestive system also mean cutting back on style. Why settle for a plain old silicone bariatric device now that you can treat yourself to a stunning and sophisticated belly piece by Cartier? Add some timeless refinement to your abdomen or show an obese loved one how much you care.” Cartier went on to announce it was including a pair of free rose-gold stomach staples with every purchase.

    Florida Students Given Lifelike Dolls To Simulate Responsibility Of Owning Slave

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  • Ozempic Can Turn Into No-zempic

    Ozempic Can Turn Into No-zempic

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    No medication in the history of modern weight loss has inspired as much awe as the latest class of obesity drugs. Wegovy and Zepbound are so effective that they are often likened to “magic” and “miracles.” Indeed, the weekly injections, which belong to a broader class known as GLP-1s, can lead to weight loss of 20 percent or more, fueling hype about a future in which many more millions of Americans take them. Major food companies including Nestlé and Conagra are considering tailoring their products to suit GLP-1 users. Underlying all this excitement is a huge assumption: They work for everyone.

    But for a lot of people, they just don’t. Anita, who lives in Arizona, told me she “took it for granted” that she would lose weight on a GLP-1 drug because “the people around me who were on it were just dropping weight like mad.” Instead, she didn’t shed any pounds. Likewise, Kathryn, from Florida, hasn’t lost any weight since starting the medication in October. “I was really hoping this was something that would be a game changer for me, but it feels like it was just a lot of wasted money,” she told me. (I’m identifying both Anita and Kathryn by their first name only to allow them to speak openly about their health issues.)

    Some people can’t tolerate the side effects of the drugs and have to stop taking them. Others simply don’t respond. For some, the strength of the dose, or length of the treatment, does not seem to make a difference. Appetites might remain robust; the “food chatter” in the brain may stay noisy. Together, both groups of less successful GLP-1 users account for a not-insignificant share of patients on these drugs—potentially up to a third. “We don’t really know why it happens, [but] we know it does happen,” Louis Aronne, an obesity-medicine specialist at Weill Cornell Medical College, told me. Despite the promise of a so-called Ozempic revolution, lots of “No-zempics” have been left behind.

    Of the two biggest reasons some people don’t lose weight on GLP-1 drugs—side effects and nonresponse—the former is much more straightforward. The GLP-1 drugs Wegovy and Zepbound (which contain the active ingredients semaglutide and tirzepatide, respectively), are known for causing potentially gnarly gastrointestinal symptoms, such as nausea and vomiting, although most people’s reactions are mild and temporary. Yet some have it far worse. Severe, albeit uncommon, side effects include pancreatitis, severe gastrointestinal distress, low blood sugar, and even hair loss, which “can push people off” the drugs, Steven Heymsfield, a professor who studies obesity at Louisiana State University, told me. In one of the biggest studies of semaglutide, encompassing more than 17,000 people over about five years, nearly 17 percent of patients discontinued the medication because of side effects.

    Far more mysterious are the people who tolerate the drugs but respond weakly to them—or sometimes not at all. Researchers have known this might happen since these drugs were in early clinical trials. About 14 percent of people who took semaglutide for obesity saw minimal impacts of less than 5 percent weight loss in one study, as did 9 to 15 percent of people who took tirzepatide in a similar one. In her own experience working with patients, “somewhere between a quarter and a third” are nonresponders, Fatima Cody Stanford, an obesity-medicine specialist at Harvard, told me, adding that it can take up to three months to determine whether the drug is working or not. That the same medication at the same dosage can lead to dramatic weight loss in one person and hardly any in another “remains confounding,” Aronne told me.

    The broad explanation is that it has something to do with genetics. The drugs work by masquerading as the appetite-suppressing hormone GLP-1 and binding to its receptor, like a key fitting into a lock. Although the lock’s overall shape is generally consistent from person to person, its nooks and crannies can vary because of genetic differences. “For some people, that key just won’t fit right,” Eduardo Grunvald, an obesity-medicine doctor at UC San Diego Health, told me. In other cases, genes may limit the effects of these drugs after they bind to GLP-1 receptors. One possibility is that people metabolize the drugs differently: Some patients may break them down too quickly for them to take effect; others may process them too slowly, potentially building up such high levels of the medications that they become toxic, Heymsfield said.

    For No-zempic patients, perhaps the most consequential impact of individual variation is on the propensity for obesity itself. “We are all very different from a genetic standpoint, in terms of our risk of weight gain,” Grunvald said. Numerous factors can drive obesity, including diet, environment, stress, and—most pertinent to GLP-1 drugs—altered brain function.

    GLP-1 drugs target a pathway that regulates appetite and insulin levels. Some cases of obesity can be caused by a disruption in that particular mechanism, in which case GLP-1s can indeed be wondrous. But “not everyone has dysfunction in this particular pathway,” Stanford said. When that is the case, the drugs won’t be very effective. A different pathway, for example, controls the absorption of fat from food; another increases energy expenditure. In these people, GLP-1s might tamp down appetite to a degree, maybe leading to some weight loss, but a different drug may be required to treat obesity at its root. “It is not all about food intake,” Stanford said.

    That’s not to say that No-zempics are out of options. They might have better success switching from one GLP-1 to the other, or even stacking them, Heymsfield said. Some patients who don’t respond to GLP-1s at all can get better results with older drugs that work on different obesity pathways, Aronne said. One, called Qysmia, a combination of the decades-old drugs phentermine and topiramate, can lead to an average weight loss of 14 percent body weight at its highest dose. If medications don’t work, bariatric surgery remains a powerful option, one that may even be growing in popularity. Last year, the number of bariatric surgeries performed in the U.S. grew despite the boom in GLP-1 usage, a trend that some expect to continue, because so many people don’t tolerate the drugs.

    The intense hype around the game-changing nature of GLP-1s makes it easy to forget that they are, in fact, just drugs. “Every drug that’s ever been made” works in some people and not in others, Heymsfield said; there’s no reason to think GLP-1s would be any different. Remembering that they are in an early stage of development has a sobering effect. Eventually, obesity drugs may leave fewer people behind. The category is expanding rapidly: By one count, more than 90 new drug candidates are in development.

    They are evolving to attack obesity from multiple fronts, which, at least in theory, widens their net of potential users. In an early study on an experimental candidate named retatrutide—called a triple agonist because it acts on GLP-1 as well as two other targets involved in obesity, GIP and glucagon receptors—100 percent of people on the highest dose lost 5 percent or more of their body weight. New candidates are also expected to have fewer side effects. They have to, Heymsfield said, because the competition is so steep that any new drug has to be “as good with less side effects, or better.”

    But no matter how good these drugs get, it’s unrealistic to think that they’ll become a one-size-fits-all treatment for everyone with obesity. The disease is simply too complex, with too many drivers, for a single type of medication to treat it. More than 200 different drugs exist for treating high blood pressure alone; in comparison, Aronne said, regulating weight is “far more complicated.” The future, rife with options, holds promise that No-zempics may find a way forward. Yet considering all the unknowns about obesity and what causes it, that may not be enough to guarantee that they will see the results they want.

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    Yasmin Tayag

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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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  • GoFundMe Is a Health-Care Utility Now

    GoFundMe Is a Health-Care Utility Now

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    GoFundMe started as a crowdfunding site for underwriting “ideas and dreams,” and, as GoFundMe’s co-founders, Andrew Ballester and Brad Damphousse, once put it, “for life’s important moments.” In the early years, it funded honeymoon trips, graduation gifts, and church missions to overseas hospitals in need. Now GoFundMe has become a go-to for patients trying to escape medical-billing nightmares.

    One study found that, in 2020, the number of U.S. campaigns related to medical causes—about 200,000—was 25 times higher than the number of such campaigns on the site in 2011. More than 500 campaigns are currently dedicated to asking for financial help for treating people, mostly kids, with spinal muscular atrophy, a neurodegenerative genetic condition. The recently approved gene therapy for young children with the condition, by the drugmaker Novartis, costs about $2.1 million for the single-dose treatment.

    Perhaps the most damning aspect of all this is that paying for expensive care with crowdfunding is no longer seen as unusual; instead, it is being normalized as part of the health system, like getting blood work done or waiting on hold for an appointment. Need a heart transplant? Start a GoFundMe in order to get on the waiting list. Resorting to GoFundMe when faced with bills has become so accepted that in some cases, patient advocates and hospital financial-aid officers recommend crowdfunding as an alternative to being sent to collections. My inbox and the Bill of the Month project (run by KFF Health News, where I am the senior contributing editor, and NPR) have become a kind of complaint desk for people who can’t afford their medical bills, and I’m gobsmacked every time a patient tells me they’ve been advised that GoFundMe is their best option.

    GoFundMe itself acknowledges the reliance of patients on the company’s platform. Ari Romio, a spokesperson for the company, said that “medical expenses” is the most common category of fundraiser it hosts. But she declined to say what proportion of campaigns are medically related, because people starting a campaign self-select the purpose of the fundraiser. They might choose the family or travel category, she said, if a child needs to go to a different state for treatment, for example. So although the company has estimated in the past that a third of the funds raised on the site are medical-related, that could be an undercount.

    Andrea Coy of Fort Collins, Colorado, turned to GoFundMe in 2021 as a last resort after an air-ambulance bill tipped her family’s finances over the edge. Her son Sebastian, then a year old, had been admitted with pneumonia to a local hospital and then transferred urgently by helicopter to Children’s Hospital Colorado in Denver when his oxygen levels dropped. REACH, the air-ambulance transport company that contracted with the hospital, was out-of-network, and billed the family nearly $65,000 for the ride—more than $28,000 of which Coy’s insurer, UnitedHealthcare, paid. Even so, REACH continued sending Coy’s family bills for the remaining balance, and later began regularly calling Coy to try to collect, enough that she felt the company was harassing her, she told me.

    Coy made multiple calls to her company’s human-resources department, REACH, and UnitedHealthcare for help in resolving the case. She applied to various patient groups for financial assistance and was rejected again and again. Eventually, she got the outstanding balance knocked down to $5,000, but even that was more than she could afford on top of the $12,000 the family owed out-of-pocket for Sebastian’s actual treatment.

    That’s when a hospital financial-aid officer suggested she try GoFundMe. But, as Coy said, “I’m not an influencer or anything like that,” so the appeal “offered only a bit of temporary relief—we’ve hit a wall.” They have gone deep into debt and hope to climb out of it.

    In an emailed response, a spokesperson for REACH noted that they could not comment on a specific case because of patient-privacy laws, but that, if the ride occurred before the federal No Surprises Act went into effect, the bill was legal. (That act protects patients from such air-ambulance bills and has been in force since January 1, 2022.) But the spokesperson added, “If a patient is experiencing a financial hardship, we work with them to find equitable solutions.” What is “equitable”—and whether that includes seeking an additional $5,000, beyond a $28,000 insurance payment, for transporting a sick child—is subjective, of course.

    In many respects, research shows, GoFundMe tends to perpetuate socioeconomic disparities that already affect medical bills and debt. If you are famous or part of a circle of friends who have money, your crowdfunding campaign is much more likely to succeed than if you are middle-class or poor. When the family of the former Olympic gymnast Mary Lou Retton started a fundraiser on another platform, *spotfund, for her recent ICU stay at a time when she was uninsured, nearly $460,000 in donations quickly poured in. (Although Retton said she could not get affordable insurance because of her preexisting condition—dozens of orthopedic surgeries—the Affordable Care Act prohibits insurers from refusing to cover people because of their prior medical histories, or charging them abnormally high rates.)

    And given the price of American health care, even the most robust fundraising can feel inadequate. If you’re looking for help to pay for a $2 million drug, even tens of thousands is a drop in the bucket.

    Rob Solomon, the CEO of the platform from 2015 to March 2020, who was named one of Time magazine’s 50 most influential people in health care, has said that he “would love nothing more than for ‘medical’ to not be a category on GoFundMe.” He told KFF Health News that “the system is terrible. It needs to be rethought and retooled. Politicians are failing us. Health-care companies are failing us. Those are realities.”

    But despite the noble ambitions of its original vision, GoFundMe is a privately held for-profit company. In 2015, the founders sold a majority stake to a venture-capital investor group led by Accel Partners and Technology Crossover Ventures. And when I asked about medical bills being the most common reason for GoFundMe campaigns, the company’s current CEO, Tim Cadogan, sounded less critical than his predecessor of the health system, whose high prices and financial cruelty have arguably made his company famous.

    “Our mission is to help people help each other,” he said. “We are not, and cannot, be the solution to complex, systemic problems that are best solved with meaningful public policy.”

    And that’s true. Despite the site’s hopeful vibe, most campaigns generate only a small fraction of the money owed. Almost all of the medical-expense campaigns in the U.S. fell short of their goal, and some raised little or no money, a 2017 study from the University of Washington found. The average campaign made it to just about 40 percent of the target amount, and there is evidence that yields—measured as a percent of their target—have gotten worse over time.

    Carol Justice, a recently retired civil servant and a longtime union member in Portland, Oregon, turned to GoFundMe after she faced a mammoth unexpected bill for bariatric surgery at Oregon Health & Science University.

    She had expected to pay about $1,000, the amount left in her deductible, after her health insurer paid the $15,000 cap on the surgery. She didn’t understand that a cap meant she would have to pay the difference if the hospital, which was in-network, charged more.

    And it did, leaving her with a bill of $18,000, to be paid all at once or in monthly $1,400 increments. “That’s more than my mortgage,” she told me. “I was facing filing for bankruptcy or losing my car and my house.” She made numerous calls to the hospital’s financial-aid office, many unanswered, and received only unfulfilled promises that “we’ll get back to you” about whether she qualified for help.

    So, Justice said, her health coach—provided by the city of Portland—suggested starting a GoFundMe. The campaign yielded about $1,400, just one monthly payment, including $200 from the health coach and $100 from an aunt. She dutifully sent each donation directly to the hospital.

    In an emailed response, the hospital system said that it couldn’t discuss individual cases, but that “financial assistance information is readily available for patients, and can be accessed at any point in a patient’s journey with OHSU. Starting in early 2019, OHSU worked to remove barriers for patients most in need by providing a quick screening for financial assistance that, if a certain threshold is met, awards financial assistance without requiring an application process.”

    This particular tale has a happy-ish ending. In desperation, Justice went to the hospital and planted herself in the financial-aid office, where she had a tearful meeting with a hospital representative who determined that—given her finances—she wouldn’t have to pay the bill.

    “I’d been through the gamut and just cried,” she said. She told me that she would like to repay the people who donated to her GoFundMe. But so far, the hospital won’t give the $1,400 back.

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    Elisabeth Rosenthal

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  • The Ozempic Plateau

    The Ozempic Plateau

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    The latest weight-loss drugs are rightly hailed as game changers for obesity, but in an important way, they are just like every other method of managing weight: They work only to a point for weight loss. The pounds melt off quickly at first and then gradually and then not at all. You can’t lose any more no matter what you do. You’ve hit the weight-loss plateau.

    It happens with dieting. It happens with bariatric surgery. And it happens now with both semaglutide (better known as Ozempic or Wegovy, depending on whether it’s prescribed for diabetes or weight loss) and tirzepatide (better known as Mounjaro or Zepbound). Weight loss triggers a set of powerful physiological changes in the body, which evolved over millions of years to keep us alive through periods of food scarcity. “Everybody plateaus,” says Jamy Ard, an obesity doctor at Wake Forest University. Exactly when varies quite a bit from person to person, but it happens after losing a certain percentage of body weight—meaning some people might plateau while still meeting the criteria for obesity.

    For Wegovy, it’s after losing, on average, 15 percent, usually more than a year into starting the drug. For Zepbound, it’s about 20 percent. These numbers are higher than is sustainable through diet and exercise alone, but they also do not reach the 30 percent achievable via the gold standard of bariatric surgery.

    These differences matter because they suggest that the level of the plateau is not permanently fixed. Recent advances in understanding the gut hormones that these drugs are designed to mimic hint at a possibility of even more powerful weight-loss drugs. Scientists are now testing ways to push the plateau down further; a drug could one day be even more effective than bariatric surgery.

    Read: Ozempic is about to be old news

    All of this raises an unsettled question: “How much weight loss is enough?” says Jonathan Campbell, who studies gut hormones at Duke. In studies, even 5 to 15 percent weight loss can substantially reverse high blood pressure, high blood sugar, and high cholesterol. Yet a patient who starts at 375 pounds with a BMI of 60 might still find themselves ineligible for a joint replacement that requires a BMI below 40, flawed as BMI may be. Or they may simply want to look thinner. The explosion of weight-loss drugs has reopened thorny questions about how they should be used, but nevertheless, pharmaceutical companies are racing ahead to develop more and more powerful ones.

    Weight loss is easiest at the beginning, before your body starts actively working against it. “Your brain doesn’t know you’re trying to lose weight on purpose,” Ard says. And once it notices, “it thinks that something is wrong.” So your body tries very, very hard to compensate.

    First of all, you become hungrier, obviously. And not just because you want to eat as much as you did before; you actually want to eat more than you did prior to losing weight. “With every one kilogram you lose, your appetite goes up above baseline by 90 or so calories per day,” says Kevin Hall, who studies metabolism at the National Institute of Diabetes and Digestive and Kidney Diseases. At the same time, your body looks for ways to conserve energy. Your muscles work more efficiently, for example, Ard says, so walking that normally burned 100 calories might now burn only 90. By making you want to eat more and burning fewer calories, your body is eventually able to slow weight loss down to zero. Here is your plateau. This is, all told, a remarkably elegant and robust system, if what you wanted to do is to maintain your weight.

    If you’re in fact trying to lose more weight, the plateau is psychologically frustrating. The same diet, the same exercise routine, the drug on which you were just losing weight will seem to have stopped working—but they haven’t. (If they did actually stop working, you would be regaining weight.) But your body is now fighting so hard against the weight loss that it requires a persistent effort just to keep the weight off, Hall says. Should you ease up, the weight will come right back, as seen in yo-yo dieting or weight regain after stopping Wegovy or Zepbound.

    The only way to get past a plateau is to up the intensity or number of interventions. Doctors might recommend, for example, bariatric surgery and a weight-loss drug. But in the future, novel drugs might be able to pharmacologically up the intensity. The progression from Wegovy to the more effective Zepbound has in fact already brought us one step closer.

    Wegovy and Zepbound both belong to a class of drugs that mimic a gut hormone called GLP-1. Both of these drugs bind GLP-1 receptors in the brain, which seems to reduce hunger. Zepbound goes a step further, though. It can also bind receptors for a second gut hormone, called GIP. Years ago, researchers noticed that bariatric surgery changes the balance of gut hormones in the body, including GLP-1 and GIP. This—and not just the physical shrinking of the stomach—is now understood to be a key driver of weight loss, to the point that bariatric surgery is sometimes called “metabolic surgery.” These observations inspired research into drugs that target not just GLP-1 but also GIP and other hormones. Essentially, they’re performing metabolic surgery with a drug rather than a scalpel.

    Read: Did scientists accidentally invent an anti-addiction drug?

    Exactly why Zepbound outperforms Wegovy is still unclear. One obvious hypothesis is that it mimics a second gut hormone; the more hormonal pathways it can influence, perhaps, the more body parts it affects and the more weight loss it triggers. And a recent clinical trial of retatrutide, a further modified derivative of Zepbound that mimics a third hormone called glucagon, demonstrated even greater weight loss: 24 percent at the highest dose.

    A second hypothesis suggests that the difference between Wegovy and Zepbound still goes back to GLP-1. Although both drugs bind that receptor, they tickle it slightly differently, setting off slightly different chain reactions. Wegovy seems to also activate some cellular machinery that acts as a break, possibly limiting its efficacy. This suggests another strategy for fine-tuning gut-hormone drugs: Companies have so far focused on trying to design one drug that binds to multiple hormone receptors, like a master key that can open three different locks. This was a practical choice, Campbell says, because trying to study three separate new drugs in clinical trials would be a logistical “nightmare.” But the optimal combination for weight loss might actually require individual keys that can jigger individual receptors in just the right way—that is, a double or triple combination of drugs.

    It may also eventually be possible to keep increasing the dosage of GLP-1 drugs to push the weight-loss plateau down. Right now, the dose is limited by what people are willing to tolerate. The drugs can cause severe nausea, vomiting, and diarrhea, so they have to be ramped up slowly over many weeks to induce tolerance and minimize side effects. But Novo Nordisk is trialing the drug in Wegovy at up to 16 milligrams a week, more than six times the current maximum dose. Tinkering with other gut-hormone pathways could also help with side effects. GIP receptors, for example, are found in neurons whose activation might suppress nausea, which may in part be why Zepbound seems to have slightly milder side effects.

    Zepbound is likely the first of many leveling-ups from single-action GLP-1 drugs. Even as the science advances, no safe method of losing weight is meant to eliminate the weight-loss plateau—and indeed, you wouldn’t want to keep losing weight indefinitely. But lose more weight? Pharmaceutical companies are betting on a market for that. With obesity drugs projected to become a $100 billion industry by 2030, they are eager for a slice of that massive pie. “The dollar signs are so big now,” Campbell says. Zepbound is the newest weight-loss drug on the block, but it too may eventually be old news.

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    Sarah Zhang

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  • Lisa Marie Presley died of complications from prior weight-loss surgery, autopsy report shows | CNN

    Lisa Marie Presley died of complications from prior weight-loss surgery, autopsy report shows | CNN

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    CNN
     — 

    A report by the Los Angeles County Medical Examiner states Lisa Marie Presley’s death in January was caused by a “sequelae of a small bowel obstruction.”

    A small bowel obstruction is a blockage in the small intestine, often because of things like scar tissue, a hernia or cancer. Without surgery, it can cause bowel tissue to die or perforate, leading to death.

    Presley’s autopsy report, obtained by CNN on Thursday, included the official opinion of deputy medical examiner Dr. Juan M. Carrillo, who attributed her small bowel obstruction to “adhesions (or, scar tissue) that developed after bariatric surgery years ago. This is a known long term complication of this type of surgery.”

    Carrillo also stated that he reviewed the autopsy toxicology results, which showed “therapeutic” levels of oxycodone in Presley’s blood – i.e., levels that are in the range of medically helpful, and not dangerous. He added that quetapine metabolite (used to treat depression, schizophrenia or manic episodes) and buprenorphine (a painkiller that can also be used to treat opioid addiction) were present but “not contributory to death.”

    “There is no evidence of injury or foul play. The manner of death is deemed natural,” Carrillo concluded.

    Dr. Michael Camilleri, a consultant and professor in the Division of Gastroenterology and Hepatology at the Mayo Clinic, told CNN on Thursday that the medications found in Presley’s may “have slowed down the motility of the intestine and would have made it perhaps more likely” for it to get “obstructed by the adhesions.”

    “Unfortunately, adhesions can happen to anybody,” he added. “And just because there were these other medications on board doesn’t necessarily mean that the person was more prone to develop the complications.”

    Lisa Marie Presley, the only daughter of the late Elvis Presley and Priscilla Presley, died hours after being hospitalized following an apparent cardiac arrest on January 12. The medical examiner’s report also detailed that she was complaining of abdominal pain on the morning of her death.

    Dr. Folasade P. May, associate professor of medicine at the David Geffen School of Medicine at UCLA and director of the Melvin and Bren Simon Gastroenterology Quality Improvement Program, told CNN Thursday that she suspects Presley “developed a cardiac arrest because she had a severe complication from the small bowel obstruction.” Neither doctor interviewed by CNN for this report was directly involved in Presley’s case.

    She was 54.

    Video shows Lisa Marie Presley on the Golden Globes red carpet

    “Priscilla Presley and the Presley family are shocked and devastated by the tragic death of their beloved Lisa Marie,” the family said in a statement at the time. “They are profoundly grateful for the support, love and prayers of everyone, and ask for privacy during this very difficult time.”

    Lisa Marie Presley’s last public appearance just days before her death was at the Golden Globe Awards, which she attended with her mother to support the Baz Luhrmann film “Elvis,” about her late father.

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  • Did Scientists Accidentally Invent an Anti-addiction Drug?

    Did Scientists Accidentally Invent an Anti-addiction Drug?

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    This article was featured in One Story to Read Today, a newsletter in which our editors recommend a single must-read from The Atlantic, Monday through Friday. Sign up for it here.

    All her life, Victoria Rutledge thought of herself as someone with an addictive personality. Her first addiction was alcohol. After she got sober in her early 30s, she replaced drinking with food and shopping, which she thought about constantly. She would spend $500 on organic groceries, only to have them go bad in her fridge. “I couldn’t stop from going to that extreme,” she told me. When she ran errands at Target, she would impulsively throw extra things—candles, makeup, skin-care products—into her cart.

    Earlier this year, she began taking semaglutide, also known as Wegovy, after being prescribed the drug for weight loss. (Colloquially, it is often referred to as Ozempic, though that is technically just the brand name for semaglutide that is marketed for diabetes treatment.) Her food thoughts quieted down. She lost weight. But most surprisingly, she walked out of Target one day and realized her cart contained only the four things she came to buy. “I’ve never done that before,” she said. The desire to shop had slipped away. The desire to drink, extinguished once, did not rush in as a replacement either. For the first time—perhaps the first time in her whole life—all of her cravings and impulses were gone. It was like a switch had flipped in her brain.

    As semaglutide has skyrocketed in popularity, patients have been sharing curious effects that go beyond just appetite suppression. They have reported losing interest in a whole range of addictive and compulsive behaviors: drinking, smoking, shopping, biting nails, picking at skin. Not everyone on the drug experiences these positive effects, to be clear, but enough that addiction researchers are paying attention. And the spate of anecdotes might really be onto something. For years now, scientists have been testing whether drugs similar to semaglutide can curb the use of alcohol, cocaine, nicotine, and opioids in lab animals—to promising results.

    Semaglutide and its chemical relatives seem to work, at least in animals, against an unusually broad array of addictive drugs, says Christian Hendershot, a psychiatrist at the University of North Carolina at Chapel Hill School of Medicine. Treatments available today tend to be specific: methadone for opioids, bupropion for smoking. But semaglutide could one day be more widely useful, as this class of drug may alter the brain’s fundamental reward circuitry. The science is still far from settled, though researchers are keen to find out more. At UNC, in fact, Hendershot is now running clinical trials to see whether semaglutide can help people quit drinking alcohol and smoking. This drug that so powerfully suppresses the desire to eat could end up suppressing the desire for a whole lot more.

    The history of semaglutide is one of welcome surprises. Originally developed for diabetes, semaglutide prompts the pancreas to release insulin by mimicking a hormone called GLP-1, or glucagon-like peptide 1. First-generation GLP-1 analogs—exenatide and liraglutide—have been on the market to treat diabetes for more than a decade. And almost immediately, doctors noticed that patients on these drugs also lost weight, an unintended but usually not unwelcome side effect. Semaglutide has been heralded as a potentially even more potent GLP-1 analog.

    Experts now believe GLP-1 analogs affect more than just the pancreas. The exact mechanism in weight loss is still unclear, but the drugs likely work in multiple ways to suppress hunger, including but not limited to slowing food’s passage through the stomach and preventing ups and downs in blood sugar. Most intriguing, it also seems to reach and act directly on the brain.

    GLP-1 analogs appear to actually bind to receptors on neurons in several parts of the brain, says Scott Kanoski, a neurobiologist at the University of Southern California. When Kanoski and his colleagues blocked these receptors in rodents, the first-generation drugs exenatide and liraglutide became less effective at reducing food intake—as if this had eliminated a key mode of action. The impulse to eat is just one kind of impulse, though. That these drugs work on the level of the brain—as well as the gut—suggests that they can suppress the urge for other things too.

    In particular, GLP-1 analogs affect dopamine pathways in the brain, a.k.a. the reward circuitry. This pathway evolved to help us survive; simplistically, food and sex trigger a dopamine hit in the brain. We feel good, and we do it again. In people with addiction, this process in the brain shifts as a consequence or cause of their addiction, or perhaps even both. They have, for example, fewer dopamine receptors in part of the brain’s reward pathway, so the same reward may bring less pleasure.

    In lab animals, addiction researchers have amassed a body of evidence that GLP-1 analogs alter the reward pathway: mice on a version of exenatide get less of a dopamine hit from alcohol; rats on the same GLP-1 drug sought out less cocaine; same for rats and oxycodone. African vervet monkeys predisposed to drinking alcohol drank less on liraglutide and exenatide. Most of the published research has been conducted with these two first-generation GLP-1 drugs, but researchers told me to expect many studies with semaglutide, with positive results, to be published soon.

    In humans, the science is much more scant. A couple of studies of exenatide in people with cocaine-use disorder were too short or small to be conclusive. Another study of the same drug in people with alcohol-use disorder found that their brain’s reward centers no longer lit up as much when shown pictures of alcohol while they were in an fMRI machine. The patients in the study as a whole, however, did not drink less on the drug, though the subset who also had obesity did. Experts say that semaglutide, if it works at all for addiction, might end up more effective in some people than others. “I don’t expect this to work for everybody,” says Anders Fink-Jensen, a psychiatrist at the University of Copenhagen who conducted the alcohol study. (Fink-Jensen has received funding from Novo Nordisk, the maker of Ozempic and Wegovy, for separate research into using GLP-1 analogs to treat weight gain from schizophrenia medication.)  Bigger and longer trials with semaglutide could prove or disprove the drug’s effectiveness in addiction—and identify whom it is best for.

    Semaglutide does not dull all pleasure, people taking the drug for weight loss told me. They could still enjoy a few bites of food or revel in finding the perfect dress; they just no longer went overboard. Anhedonia, or a general diminished ability to experience pleasure, also hasn’t shown up in cohorts of people who take the drug for diabetes, says Elisabet Jerlhag Holm, an addiction researcher at the University of Gothenburg. Instead, those I talked with said their mind simply no longer raced in obsessive loops. “It was a huge relief,” says Kimberly Smith, who used to struggle to eat in moderation. For patients like her, the drug tamed behaviors that had reached a level of unhealthiness.

    The types of behaviors in which patients have reported unexpected changes include both the addictive, such as smoking or drinking, and the compulsive, such as skin picking or nail biting. (Unlike addiction, compulsion concerns behaviors that aren’t meant to be pleasurable.) And although there is a body of animal research into GLP-1 analogues and addiction, there is virtually none on nonfood compulsions. Still, addictions and compulsions are likely governed by overlapping reward pathways in the brain, and semaglutide might have an effect on both. Two months into taking the drug, Mary Maher woke up one day to realize that the skin on her back—which she had picked compulsively for years—had healed. She used to bleed so much from the picking that she avoided wearing white. Maher hadn’t even noticed she had stopped picking what must have been weeks before. “I couldn’t believe it,” she told me. The urge had simply melted away.

    The long-term impacts of semaglutide, especially on the brain, remain unknown. In diabetes and obesity, semaglutide is supposed to be a lifelong medication, and its most dramatic effects are quickly reversed when people go off. “The weight comes back; the suppression of appetite goes away,” says Janice Jin Hwang, an obesity doctor at UNC School of Medicine. The same could be true in at least certain forms of addiction too. Doctors have noted a curious link between addiction and another obesity treatment: Patients who undergo bariatric surgery sometimes experience “addiction transfer,” where their impulsive behaviors move from food to alcohol or drugs. Bariatric surgery works, in part, by increasing natural levels of GLP-1, but whether the same transfer can happen with GLP-1 drugs still needs to be studied in longer trials. Semaglutide is a relatively new drug, approved for diabetes since 2017. Understanding the upshot of taking it for decades is, well, decades into the future.

    Maher told me she hopes to stay on the drug forever. “It’s incredibly validating,” she said, to realize her struggles have been a matter of biology, not willpower. Before getting on semaglutide, she had spent 30 years trying to lose weight by counting calories and exercising. She ran 15 half marathons. She did lose weight, but she could never keep it off. On semaglutide, the obsessions about food that plagued her even when she was skinny are gone. Not only has she stopped picking her skin; she’s also stopped biting her nails. Her mind is quieter now, more peaceful. “This has changed my thought processes in a way that has just improved my life so much,” she said. She would like to keep it that way.

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    Sarah Zhang

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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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  • Ozempic Is About to Be Old News

    Ozempic Is About to Be Old News

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    All of a sudden, Ozempic is everywhere. The weight-loss drug that it contains, semaglutide, is a potent treatment for obesity, and Hollywood and TikTok celebrities have turned it into a sensation. In just a few months, the medication has been branded as “revolutionary” and “game-changing,” with the power to permanently alter society’s conceptions of fatness and thinness. Certainly, a drug like semaglutide could be all of those things: Never in the history of medicine has one so safely led to such dramatic weight loss in so many people.

    But let’s not get ahead of ourselves. As weight-loss medications go, Ozempic is far from perfect. Though the drug has profound impacts, it requires weekly injections, a tolerance for uncomfortable side effects, and the stamina—not to mention the budget—for long-term treatment. (Ozempic has somehow become a catchall term for semaglutide but technically that product has gotten FDA sign-off only as a diabetes medication. A larger dose of semaglutide, marketed as Wegovy, has been approved for weight loss.)

    Made by the Danish drugmaker Novo Nordisk, semaglutide dominates the U.S. weight-loss market right now, but its reign might be short-lived. The colossal demand for these drugs has spurred a competition in the pharmaceutical industry to develop even more potent and powerful medications. The first of them could become available as soon as this summer. For all its hype, semaglutide is the stepping stone and not the final destination of a new class of obesity drugs. Just how good they get, and how quickly, will go a long way in determining whether this pharmaceutical revolution actually meets its full promise.

    In a sense, semaglutide hardly represents a major step forward in science. Diet drugs are nothing new, and even the category of pharmaceuticals that these new products belong to, called “GLP-1 agonists,” has been around for several years. These drugs mimic the hormone GLP-1 (glucagon-like peptide one) and bind to its receptor in the body. This triggers a sense of fullness associated with having just eaten, and also slows the release of food from the stomach. (It also increases insulin secretion, keeping blood sugar in check, which is why Ozempic is still intended as a diabetes drug.) Already, these pharmaceuticals have gotten better over time: A daily injection called liraglutide and sold as Saxenda, which was approved by the FDA in 2014 for obesity, leads to the loss of 5 to 10 percent of a person’s body weight in most cases. But one reason semaglutide took off in a way that liraglutide didn’t is that it can lead to weight loss of up to 20 percent. “Now you have a shot that’s once a week instead of every day, you’re making dramatic improvements, and people notice more,” Angela Fitch, the president of the Obesity Medicine Association and the chief medical officer of the obesity-care start-up Knownwell, told me.

    But not everyone who takes these drugs can achieve that level of weight loss. More than 60 percent of those on Wegovy experience smaller changes, in part because the drug can’t account for the complex drivers of obesity that aren’t related to food. The next generation of drugs is reaching for more. The first leap forward is Mounjaro, known generically as tirzepatide, a diabetes drug from Eli Lilly that the FDA is expected to approve for weight loss this year. In one study, it led to 20 percent or more weight loss in up to 57 percent of people who took the highest dose; The Wall Street Journal recently called it the “King Kong” of weight-loss drugs. People on Mounjaro tend to lose more weight more quickly and generally have a “better experience” than those on Wegovy, Keith Tapper, a biotech analyst at BMO Capital Markets, told me. It’s also cheaper, though by no means cheap, at roughly $980 for the highest-dose option, he said; a dose of Wegovy costs about $1,350.

    These leaps in potency are happening on the molecular level. Like semaglutide, Mounjaro mimics the effects of GLP-1, but it also hits receptors for another hormone—GIP. That leads to even more weight loss by further attenuating focus on food and potentially also increasing the activity of a fat-burning enzyme, said Tapper. So-called dual-agonist drugs “offer a step change” in both weight loss and blood-sugar control, he added.

    And why stop at two receptors when so many others are involved in regulating hunger? “This area is exploding in terms of research and testing different combinations of hormones,” which are still poorly understood, Shauna Levy, a professor specializing in bariatric surgery at Tulane University School of Medicine, told me. Eli Lilly has another drug in the works that targets three receptors; one from the drugmaker Amgen works by “putting the brakes” on the GIP receptor and “putting the gas” on GLP-1’s, a company spokesperson told me. Several other companies have already joined what some have dubbed a “race” to develop the next great obesity drug, in which Lilly, Pfizer, Amgen, Structure Therapeutics, and Viking Therapeutics are expected to be the front-runners, said Tapper.

    The potency of weight-less drugs is not the only factor that will determine the shape of their future trajectory. Wegovy and Mounjaro injections are tolerable for most people, but they are less convenient than a pill. Making oral versions of these drugs isn’t as easy as packing everything into a capsule, though. Semaglutide is a molecule that gets chewed up in the stomach. For this reason, the semaglutide pill Rybelsus, which is already approved for diabetes, leads to far less dramatic weight loss than its injectable kin. But drugmakers are undeterred by this complication, because a pill even more powerful than semaglutide would no doubt have many customers. In January, Pfizer’s CEO Albert Bourla said that an oral weight-loss drug “unlocks the market,” which he estimated could eventually be worth $90 billion. Pfizer doesn’t have any weight-loss drugs yet but is developing a twice-daily GLP-1 agonist pill; Eli Lilly also has an oral version in the works. Tapper expects those drugs to become available in 2026, and a similar offering from Structure Therapeutics is likely to follow the next year.

    Drugmakers will also likely vie to create drugs with fewer side effects. Novo Nordisk notes that gastrointestinal issues are common with semaglutide; accounts of horrible nausea, constipation, and vomiting have proliferated online. As one actor put it to New York Magazine, people on Ozempic are “shitting their brains out.” With Wegovy, more serious issues, such as pancreatitis, thyroid cancer, and kidney failure, are also possible but are considered rare. Although nothing to scoff at, side effects tend to subside with prolonged treatment and can usually be managed with help from a doctor, said both Fitch and Levy, who regularly prescribe semaglutide to patients with obesity. It’s possible, Levy added, that people experiencing really terrible effects may be getting their drugs from shady compounding pharmacies or even from other countries.

    The fact that people are turning to sketchy outlets to get weight-loss drugs underscores the biggest issue with them: access. Medicare and most private insurance companies don’t cover anti-obesity drugs. (Such drugs are classified as “cosmetic” by the Centers for Medicare and Medicaid Services, and thus don’t qualify for coverage.) “I am hopeful that the price will come down with more competition,” Fitch told me. But there’s no guarantee that will happen: Competition typically makes a product cheaper over time, but research suggests that isn’t always the case in pharmaceuticals. Even if the drugs do become cheaper, they may not become cheap enough. The oral forms of these drugs, some of which could be available by 2026, are expected to cost about $500 a month, Tapper said. By 2030, the cost of obesity drugs could come down to about $350 a month, according to a recent Morgan Stanley analysis, which would still be out of reach for many Americans.

    Levy estimates that the next five years will bring about a “huge explosion” of next-gen obesity drugs. In that case, the market will likely expand to accommodate a variety of drugs with different price points and efficacies. Some people may aim to lose 20 or more percent of their body weight; some may be content with less. The market is so diverse that it will likely “support a broad range of options,” said Tapper, such as cheaper, lower-dose oral drugs for people who have milder medical issues, and more expensive injectables for those with more severe medical concerns. That opens up the possibility that medically mediated weight loss could soon be an option for a far greater proportion of people.

    Regardless of how much these drugs’ costs may decrease, they will always add up if people are paying out of pocket for them. They are meant to be taken long term: Once a person stops taking Wegovy, the weight tends to come right back. The current crop of weight-loss medications are essentially maintenance drugs, much like the cholesterol-busting drug Lipitor, which is taken daily to treat long-term disease. But Lipitor, unlike obesity drugs, is generally covered by insurance. Unless obesity drugs receive the same kind of coverage, no level of improvement will lead them to deliver on what Ozempic is promising us now.

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    Yasmin Tayag

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  • New Guidelines for Kids With Obesity: What Parents Should Know

    New Guidelines for Kids With Obesity: What Parents Should Know

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    Jan. 13, 2023 — The American Academy of Pediatrics last week issued their first new guidelines in 15 years for evaluating and treating kids and adolescents with overweight or obesity. 

    If you only saw the headlines, you might think that when a youngster is a few pounds overweight, their pediatrician will prescribe a weight loss drug or bariatric surgery. The reality is much less alarming. The guidelines take a deep dive into evidence-based treatments at various levels.

    “It’s a misunderstanding, it’s being sensationalized,” says Lori Fishman, PsyD, a child psychologist who specializes in pediatric weight management. “There’s so much more to the process. It’ll be a small percentage of kids who’ll even qualify for these treatments.” 

    Treating the Whole Child

    Before writing the guidelines, the AAP’s Subcommittee on Obesity spent years analyzing and synthesizing information from nearly 400 studies. 

    “We now have more information than ever that supports that obesity is a chronic, complex disease that requires a whole-child approach,” says Sarah Hampl, MD, one of two lead authors of the guidelines. “And many kids will not outgrow it, so it’s important to identify children with obesity early and offer them evidence-based treatments.”

    In the new guidelines, treatment of overweight and obesity doesn’t mean putting a kid on a diet and expecting their parents to manage it. Instead, multi-pronged approaches might include nutrition support, physical activity specialists, behavioral therapy, medications for adolescents 12 and up, and surgery for teenagers with severe obesity. 

    Before starting any of these evidence-based treatments, the guidelines remind pediatricians to consider each child’s individual circumstances — their living situation, their access to healthy food, and more.

    “As pediatricians, we ought to be especially mindful of the influences that child and family are surrounded by,” Hampl says. “We should help guide them, whether it’s to local resources for healthy food or support for a child who’s being bullied.”

    Because obesity is often stigmatized, the pediatricians’ group also included guidance for pediatricians to help them examine their own biases. It calls on them to acknowledge the myriad genetic and environmental factors that contribute to obesity and treat children and their parents with respect and sensitivity.

    The Rise of Childhood Obesity

    For kids 2-18, obesity is defined as having a BMI at or above the 95th percentile for a child’s age and sex. Rates of pediatric obesity have more than tripled since the 1960s, from 5% to nearly 20%. Just last month, the CDC released updated growth charts to take into account how many more children and adolescents now have severe obesity, well beyond the 95th percentile. By 2018, more than 4.5 million kids qualified, but the old charts didn’t go high enough.

    If these trends continue, researchers estimate that 57% of children aged 2 to 19 will have obesity by the time they hit 35. And the pandemic has only made things worse.

    “It’s about much more than what we eat and drink or how physically active we are,” Hampl says. Risk factors for obesity include genetics, socioeconomics, race and ethnicity, government policies, a child’s environment, neighborhood, and school, and even their exposure to unhealthy food marketing. Because each child is so different, these factors combine in unique ways.

    You can see an example of the variability in Jill’s family. She’s a New Jersey mom with two teenage sons. For privacy reasons, we’re using only her first name. 

    “I have two children who I raised the same way, who were offered the same foods, and yet one weighs 80 pounds more than the other,” she says. “My 16-year-old is happy to choose fruit over a cookie. He’s able to stop, to not eat another bite. The 14-year-old will eat cookies until they’re gone.”

    No More Watch and Wait

    The last set of guidelines, from 2007, called for pediatricians to monitor kids with obesity via “watchful waiting.” It would give children a chance to outgrow their excess pounds before being treated. Research conducted since then shows that’s not effective. 

    “The risk of watching and waiting, in my experience, is that a 10-pound-overweight child a year later might be 30 pounds overweight,” says Fishman. “That’s a lot harder to tackle.”

    In the new guidelines, the AAP stresses the urgency of treating children with overweight and obesity as soon as it’s diagnosed. Instead of hoping a growth spurt might take care of the problem, pediatricians should move quickly, “at the highest level of intensity appropriate for and available to the child.”

    By guiding children and their families to adopt healthier habits early, it may help to reduce some of the weight-related health issues that have also increased in the last few decades. Just within the 21st century, diabetes rates for children and teenagers have skyrocketed — between 2001 and 2017, the number of kids with type 2 went up an astonishing 95%.

    “Now we understand the consequences of untreated obesity, especially severe obesity,” says Mary Ellen Vajravelu, MD, a doctor-scientist at the Center for Pediatric Research in Obesity and Metabolism in Pittsburgh. “That includes type 2 diabetes, fatty liver disease, high blood pressure, high cholesterol. It’s important to treat obesity in childhood to avoid the complications we’re seeing in young adults.”

    Also important: Reversing the trend while a child is young can help them avoid the emotional impact of growing up with obesity. 

    “I saw the recommendations and thought, ‘How different would my life have been for the past 35 years if they had treated my obesity when I was a child?” says Heather, the mother of a 10-year-old in Florida. She’s been carrying shame and limiting herself since childhood, for instance by avoiding activities where her size might prove embarrassing. “For kids who are struggling, I think it’ll be life-changing.”

    What the Guidelines Really Say

    In a world where fat-shaming is rampant, parents often want to protect their children by encouraging them to lose weight — but parental pressure adds another layer of bad feelings. The AAP advises against putting a child on a diet or restricting their access to food without professional help. Guidelines recommend that pediatricians:

    • Treat obesity as a chronic disease. That calls for long-term care strategies and ongoing monitoring.
    • Implement a model known as the “medical home.” It takes treatment beyond the exam room to shape behavior and lifestyle changes. Pediatricians should build partnerships with families in their care and serve as a care coordinator, working with a team that may include obesity treatment specialists, dietitians, psychologists, nurses, exercise specialists, and social workers.
    • Use a patient-centered counseling style called motivational interviewing. Rather than a doctor prescribing changes for a child’s family to figure out, the process guides families to identify which behaviors to adjust based on their own priorities and goals — that might mean cutting back on sugary drinks or walking together after dinner. Research has shown it takes less than 5 hours of motivational interviewing with a pediatrician or dietitian to help bring down BMI.
    • Opt for an approach called intensive health behavior and lifestyle treatment (IHBLT) whenever feasible. As the name suggests, it’s an intense treatment that calls for at least 26 hours of face-to-face, family counseling on nutrition and exercise over a period of 3 to 12 months. More sessions produce larger reductions in BMI, with 52 hours or more over the same duration having the greatest impact. Unfortunately this treatment program isn’t available everywhere, and for many families the time and financial demands put it out of reach.
    • Offer approved weight loss drugs to adolescents 12 years and older who have obesity. Medication should always be used together with nutrition and exercise therapies.
    • Refer adolescents 13 and up with severe obesity for possible weight loss surgery. That referral should be to a surgical center with experience in working with adolescents and their families, where the teen would undergo a thorough screening process.

    Medication and Surgery

    Those last two recommendations have garnered most of the headlines, and it’s understandable. Medicating a child — or performing an operation that would permanently change their body — might seem extreme. But the research shows that for children with obesity and severe obesity, these treatments work.

    “This isn’t for a kid who’s a little overweight,” says Fishman. “It’s obesity that’s limiting this child’s ability to function. When we face something this disabling, we want to attack it from every direction we can.”

    Right now, only a handful of medications are approved to treat obesity in adolescents. Some are taken orally, while others, like the recently approved Wegovy, are injected. 

    Jill, the New Jersey mom, is using Wegovy herself. 

    “The fact that I’ve had success with it makes me more comfortable about approaching it as an option for my son,” she says. “And ultimately, it’s his choice. If he wants to see if he can just do things differently first, we’ll try that. A nutritionist’s guidance will be part of this for him regardless, so he can understand what’s involved. It’s not like he’ll get the shot and all of a sudden magic happens.”

    Losing weight with medication can help remove some of the shame that often comes with obesity. Heather, the Florida mom, is also using an injectable drug.

    “It’s all the morality stuff like, if you had more self-control, if you worked harder and really tried, if you just made the choice,” she says. “This pulls all the morality out of it. Obesity is a medical condition. It’s so clear. In the same way I take thyroxin because my thyroid doesn’t work well, this makes my insulin receptors work properly.”

    For kids 13 and older with severe obesity — a BMI over 35, or 120% of the 95th percentile for age and sex — metabolic or bariatric surgery may be recommended. Of course, surgery is much more invasive than medication, with a greater risk of complications. The guidelines acknowledge this and stress the need for thorough screening before proceeding.

    “The pediatrician would refer a child for evaluation. They wouldn’t say, ‘You definitely need to have surgery,’” Hampl says. “They’d say, ‘As your pediatrician, I feel that you would benefit from a comprehensive evaluation at a pediatric bariatric surgical center.’ These types of centers do a very thorough pre-op evaluation over at least 6 months, and then careful monitoring is done for years afterward.”

    Weight loss surgery for adolescents does have certain drawbacks. Any surgery has the risk of complications, and some surgical patients do gain back a significant amount of weight. Some research suggests that adolescents who have the surgery are more likely to have alcohol problems later in life.

    Even with those risks, for some teens surgery may prove life-saving.

    “We know much more about the complications of obesity in adults, we know those are devastating,” says Hampl. “If we can prevent heart attacks, stroke, sleep apnea, diabetes, and other really serious medical complications, that in itself is a huge benefit to the person’s health.”

    The Question of Equity

    The guidelines point out that obesity has inequities baked into the condition. Risk factors increase depending on your economic status and your race. Access to treatment is lopsided. Some of the most effective treatments, like intensive health behavior and lifestyle treatment, aren’t available everywhere. Providers may not be in-network or even accept insurance. 

    If the family of a child with overweight can’t access effective programs to help them build healthy habits, the child’s odds for developing obesity grow. As they get older and their BMI reaches the level of obesity or severe obesity, treatments like medication and surgery become an option. But they’re even more costly, which leaves many families with no help at all.

    That’s why the guidelines also include policy recommendations aimed at covering comprehensive obesity prevention, evaluation, and treatment. They call attention to the ways unhealthy food is marketed, the effects of limited resources on a community, how socioeconomic and immigration status factor in, and the challenges posed by food insecurity.

    “We hope the guidelines will serve as impetus to help improve access to care for all children with obesity,” Hampl says. “That includes everything from infrastructure and policy to systems change as well.”

    For parents who struggle to help their children with overweight and obesity, having such an authoritative resource can pave the way to getting real help.

    “It’s good that they issued these guidelines. I’m hoping, for my son and all the kids out there who are struggling, that it will help to have it recognized as something worthy of clinical, medical management,” Jill says. “It’s validating.” 

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