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  • The Future of Obesity Drugs Just Got Way More Real

    The Future of Obesity Drugs Just Got Way More Real

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    A wild idea recently circulated about the future of aviation: If passengers lose weight via obesity drugs, airlines could potentially cut down on fuel costs. In September, analysts at Jefferies Bank estimated that in the “slimmer society” obesity drugs will create, United Airlines could save up to $80 million in jet fuel annually.

    In the past year, as more Americans have learned about semaglutide, which is sold for diabetes under the brand name Ozempic and for obesity under the name Wegovy, hype has become completely divorced from reality. For all the grand predictions, just a fraction of Americans who qualify for obesity drugs are on them. With a list price of roughly $1,350 a month, Wegovy is far too expensive, under-covered by insurance, and in limited supply to be a routine part of health care.

    But that possibility is beginning to seem very real. The results of a highly anticipated study published on Saturday indicate that Wegovy can have profound effects on heart health, which potentially opens up the drug to even more patients. A few days earlier, the FDA approved Zepbound, an obesity drug that is a bit cheaper and appears more potent than Wegovy. If there was any doubt before, now it is undeniable: Obesity drugs “are here to stay,” Kyla Lara-Breitinger, a cardiologist at the Mayo Clinic, told me. “There’s only going to be more and more of them.” They are now poised to become deeply entrenched in American health care, perhaps eventually even joining the ranks of commonly used drugs such as statins and metformin.

    Considering that obesity is linked to all sorts of major heart ailments, it is no big surprise that a weekly shot for weight loss might have some cardiovascular benefits. But because this class of obesity drugs, known as GLP-1 agonists for the hunger hormone they target, is so new, doctors did not know that for sure. Starting in 2018, Novo Nordisk, the company that manufactures semaglutide, began to look for answers in a study of more than 17,600 people with obesity and cardiovascular disease. In this group, results of a trial named SELECT show that Wegovy reduced the risk of major cardiac events—stroke, heart attack, death—by 20 percent. Even compared with studies on common heart medications such as Praluent and Repatha, the Wegovy results are “impressive,” Eugene Yang, a cardiologist and professor of medicine at the University of Washington, told me.

    How exactly the drug prevents major cardiac events isn’t fully understood. Some of the effects can likely be chalked up to weight loss itself, which is associated with improvements in metrics that influence heart health, such as blood pressure, Yang said. But mechanisms independent of weight loss may also be at work. In the trial, lower rates of cardiovascular events began showing up before participants lost weight. One explanation is the drug’s impact on inflammation, which is associated with heart disease: C-reactive protein, a rough proxy for inflammation, dropped by nearly 40 percent in study participants.

    Regardless of how Wegovy works, Yang said, “it has the potential benefit of being very significant” as a new line of treatment for heart disease, the leading cause of death nationwide. Novo Nordisk has already applied for expanded FDA approval and anticipates receiving it within six months. Approval would also show that Wegovy has a medical benefit beyond weight loss, pressuring insurers to cover it. Right now, for instance, Medicare does not, in part because obesity has long been viewed as a cosmetic issue, not a medical one. Even with private coverage, the drug is still frequently out of reach. The SELECT trial makes it “unequivocally clear” that obesity is a health condition that can be treated with drugs, Ted Kyle, an obesity-policy expert, told me. Still, the study leaves room for pushback: The absolute risk reduction of cardiovascular events was 1.5 percent, which is, by some reckonings, quite small. A higher risk reduction would have “put more pressure” on insurers and manufacturers to make the drugs more affordable for Americans, Lara-Breitinger said.

    Still, the findings are robust enough that it seems likely that the heart benefits of obesity drugs will lead more Americans to take them—if not immediately, then eventually. The approval of a new drug could do the same. Tirzepatide, which Eli Lilly has sold as a diabetes drug under the name Mounjaro, will be marketed as Zepbound for obesity—and it is coming for Wegovy’s throne. In one study, people on tirzepatide lost an average of 18 percent of their body weight; for comparison, in another study patients on Wegovy lost an average of 15 percent. At a little over $1,000 a month, Zepbound is not cheap, but its list price is hundreds of dollars lower than that of Wegovy. (The manufacturers of both drugs have said that most insured patients pay far less than that.)

    Zepbound’s approval is just the beginning. Unlike semaglutide, which targets only one hormone, GLP-1, to exert its effects on appetite and fullness, tirzepatide targets two. Other drugs that target two or even three hormones are in the works, as are versions that come in a more appealing pill format rather than as an injection. Generic versions of these drugs, likely beginning with liraglutide, a predecessor to semaglutide sold as Saxenda, could become available soon, Yang said. This competition will help bring down costs, but it will go only so far. Drug pricing is “a little bit screwy,” Kyle said, complicated by the wide gap between the list price and the net price created by manufactures, insurers, and intermediaries between them.

    Each new competitor and new study is a step toward a future in which a substantial proportion of Americans with obesity are routinely prescribed these drugs. In a single week, obesity drugs leapt a new era—one in which they are about to become significantly more mainstream. No doubt that future is a bright one for millions of people who might benefit from treatment. Still, many questions about the drugs remain unanswered, such as their long-term safety and endless supply shortages.

    But the potential for obesity drugs to truly change America has never felt closer—with all of the dizzying questions this creates about what “a slimming society” might mean for exercise, the food industry, and apparently even airline jet fuel.

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    Yasmin Tayag

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  • Can You Have a Fun Vacation on Ozempic?

    Can You Have a Fun Vacation on Ozempic?

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    At Christmas dinner, Jenny Burriss remembers eating exactly one bite of beef before feeling full. She had just upped her dose of semaglutide—the diabetes and obesity drug better known by the brand names Ozempic and Wegovy—and her appetite had plummeted. She had also lost her taste for alcohol, a side effect of the drug. So before her vacation a couple of months later, she decided to skip a dose. She was going to Disney World, and she wanted to enjoy the food—at least a little.

    She was indeed hungrier after skipping her weekly injection, but not ravenously so. At the Biergarten buffet in Epcot’s Germany pavilion—where she might have once piled her plate high, justifying to herself that, after all, this is vacation—she was satisfied by just a small taste of everything. At the French pavilion, she savored a Grand Marnier orange slush. She didn’t lose weight at Disney World, but she didn’t gain any either.

    Semaglutide works by suppressing the appetite and promoting a feeling of fullness. More fundamentally though, it works by altering one’s relationship with food. Doctors see the drug as a powerful biochemical tool to help patients build healthy long-term habits. Eating becomes a source not of comfort or pleasure, but simply of sustenance. “It takes a little bit of the enjoyment out of it,” Burriss told me. “But that’s healthy,” she added, for someone like her, who had a compulsive relationship with food. Semaglutide has helped her lose about 40 pounds. As the drug has exploded in popularity for weight loss, though, people who use semaglutide to reset their eating habits are navigating a world where food and the anticipation of it are still central to celebration. Semaglutide is meant to be taken regularly as a lifelong drug. So what to do on vacation, when enjoyment is kind of the point?

    For some, deciding to forgo the dose while traveling is just a practical consideration. Semaglutide’s side effects usually taper off as the body adjusts, but they can range from the mildly inconvenient to the terribly uncomfortable: nausea, vomiting, fatigue, constipation, diarrhea, heartburn, sulfur burps. No one wants to get hit with a bout of diarrhea as a plane is taking off.

    For others, staying on the drug removes the compulsion and distraction of thinking about food. They enjoy that peace, even on vacation. Semaglutide quiets what some patients call the “food noise” in their brains: waking up in the morning and immediately wondering what to eat today. Mexican? Pizza? Oh, let me look at some menus. It can be overwhelming to experience and exhausting to constantly counter. Fatima Cody Stanford, an obesity-medicine doctor at Harvard, told me that her patients on semaglutide like being able to attend a wedding or a party “without having to worry about overindulging.” Janice Jin Hwang, an obesity-medicine doctor at the UNC School of Medicine, says she tells patients not to see vacations as cheat days. “I don’t like to make it a dichotomy where it’s your normal time and your vacation time,” she says, advocating instead for a more balanced approach all the time.

    People who want to skip while on vacation, though, are swapping tips and experiences online, sometimes in lieu of official medical advice. By and large, those I spoke with, like Burriss, told me that they were looking for a middle ground, not to go completely overboard on food. “I certainly didn’t want to pig out,” says Sarah, who skipped a dose for a 10-year-anniversary trip to the Bahamas. “I just didn’t want to have that weird nauseous feeling or not be able to enjoy wine.” Sarah, whose last name I’m not using to protect her medical privacy, has always loved researching the best restaurants on vacation. This time, she felt some of the thrill of anticipation, but she ate moderately and chose healthy options, such as fresh fish. Allyson Gelman, who skipped while on vacation in Mexico City, told me she still ended up canceling an eagerly awaited 12-course tasting menu. When she eats too much or too unhealthily on semaglutide, she has to vomit; she’s sometimes had to run to the bathroom after overdoing it in a nice restaurant. In Mexico City, she could still feel the drug’s effects lingering in her system, and she knew she wasn’t getting through 12 courses without throwing up.

    Semaglutide does take several weeks to clear from the body, so skipping just one dose attenuates but doesn’t eliminate the effects of the drug. Marnie, whom I’m also identifying by only her first name for medical privacy, has been regularly taking her prescribed Wegovy every other week. In the second week, she can feel her side effects start to fade and her hunger start to return. For her, skipping is largely about managing her side effects, because the drug still leaves her very tired. She’s probably losing weight more slowly this way, she says, but she’s okay with that. In certain cases, Stanford, the doctor at Harvard, told me she has instructed patients who don’t need the full dose for weight loss to go longer between injections to modulate severe side effects. (Bafflingly, she’s found that insurance won’t cover a smaller-dose injection pen.)

    The explosion of interest in semaglutide is so new, though, that doctors and patients alike are still figuring out what it means in the long term—not just in two or three years, but in 20 or 30. How long do the effects last, and how permanent are these new habits? Burriss believes that, for her, there is room for the occasional indulgence, during a special event or vacation. “It’s not an everyday thing,” she said. And indulging while on semaglutide is still nothing like bingeing without it.

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    Sarah Zhang

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