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  • The Ozempic Revolution Is Stuck

    The Ozempic Revolution Is Stuck

    Millions more Americans are now eligible for obesity drugs. But the injections remain maddeningly hard to find.

    Illustration by The Atlantic. Source: Getty.

    The irony undergirding the new wave of obesity drugs is that they initially weren’t created for obesity at all. The weight loss spurred by Ozempic, a diabetes drug in the class of so-called GLP-1 agonists, gave way to Wegovy—the same drug, repackaged for obesity. Zepbound, another medication, soon followed. Now these drugs have a new purpose: heart health.

    On Friday, the FDA approved the use of Wegovy for reducing the risk of heart attack, stroke, and death in adults who are overweight and have cardiovascular disease. The move had been anticipated since the publication of a landmark trial in the fall, which showed the drug’s profound effects on cardiovascular  health. The decision could usher in a new era where GLP-1 drugs become mainstream, opening up access to millions of Americans who previously didn’t qualify for Wegovy.

    Some of the obstacles stopping people from getting the drug may also begin to crumble. Insurance companies commonly deny coverage of Wegovy because obesity is seen as a cosmetic concern rather than a medical one, but that argument may not hold up for cardiovascular disease. “This new FDA indication is HUGE,” Katherine Saunders, an obesity-medicine physician at Weill Cornell Medicine, told me in an email. Wegovy may soon be within reach for many more Americans—that is, if they can find it.

    In practice, Wegovy is maddeningly hard to get hold of. Shortages of injectable semaglutide, the active ingredient in Wegovy and Ozempic, have been ongoing since March 2022; currently, most doses of Wegovy are in limited supply. As the popularity of semaglutide has skyrocketed, demand has completely outstripped the capacity of its manufacturer, Novo Nordisk. The drug comes in injection pens containing a glass vial; “these are not easy products to make,” Lars Fruergaard Jørgensen, the CEO of Novo Nordisk, said in August. In response to the shortages, the company withheld its supply of lower Wegovy doses last year. Because treatment on the medication must begin in low doses, this meant that new patients who wanted to start on Wegovy functionally couldn’t. In January, the company began “more than doubling the amount of the lower-dose strengths” of the drug, a Novo Nordisk spokesperson told me, and it plans to gradually increase overall supply throughout the rest of the year.

    The ongoing shortages have left providers and patients feeling stuck. “It is devastating to prescribe a lifesaving medication for a patient and then find out it’s not covered or we can’t locate supply,” Saunders said. Doctors are scrambling to make do with what’s available. Ivania Rizo, an endocrinologist at Boston Medical Center, told me she has had to turn to older GLP-1 drugs such as Saxenda to “bridge” patients to higher doses of Wegovy, although now that is in shortage too. Patients can spend each day calling pharmacy after pharmacy in search of one with Wegovy in stock, Rizo said. In desperation, some have turned to versions of the drug that are custom-made by compounding pharmacies with little oversight, despite the FDA expressing concerns about them. The shots are supposed to be taken weekly, but others have attempted to stretch their doses beyond that.

    That the new FDA approval could very mainstream obesity drugs may create long-needed pressure to help resolve these shortages. It makes clear that Wegovy is a lifesaving medication not only for people with obesity but also for those with cardiovascular disease—the leading cause of death in the U.S.—putting the impetus on Novo Nordisk to ramp up production. But in the short term, the access issues may persist. “The new approval is very likely to worsen shortages, because the demand for Wegovy will continue to climb—now at an even faster pace,” Saunders said.

    If patients think they’re stuck now, they’re about to feel entrenched. Wegovy is the only obesity drug that has been approved to reduce the risk of heart attacks, but none of its competitors is easily available either. Supplies of certain dosages of Eli Lilly’s Mounjaro, a diabetes drug whose active ingredient is sold for obesity as Zepbound, are limited, and shortages are expected later this year. “We need supply to increase dramatically,” Saunders said. Both Novo Nordisk and Eli Lilly have invested heavily in expanding production capacity, but some of the new plants won’t open until 2029.

    For all of its advantages, the FDA approval has a sobering effect on the unrelenting hype around GLP-1s. So much of the excitement around obesity drugs has focused on the future, as dozens of pharmaceutical companies develop more powerful drugs, and commentators imagine a world without obesity. In the process, the issues of the present have gone overlooked. More drugs won’t make much of a difference if the drugs themselves are out of reach.

    Yasmin Tayag

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  • Ozempic Makes You Lose More Than Fat

    Ozempic Makes You Lose More Than Fat


    The newest and much-hyped obesity drugs are, at their core, powerful appetite suppressants. When you eat fewer calories than you burn, the body starts scavenging itself, breaking down fat, of course, but also muscle. About a quarter to a third of the weight shed is lean body mass, and most of that is muscle.

    Muscle loss is not inherently bad. As people lose fat, they need less muscle to support the weight of their body. And the muscle that goes first tends to be low quality and streaked with fat. Doctors grow concerned when people start to feel weak in everyday life—while picking up the grandkids, for example, or shoveling the driveway. Taken further, the progressive loss of muscle can make patients, especially elderly ones who already have less muscle to spare, frail and vulnerable to falls. People trying to slim down from an already healthy weight, who have less fat to spare, may also be prone to losing muscle. “You have to pull calories from somewhere,” says Robert Kushner, an obesity-medicine doctor at Northwestern University, who was also an investigator in a key trial for one of these drugs.

    Kushner worries about patients who start with low muscle mass and go on to become super responders to the drugs, losing significantly more than the average 15 to 20 percent of their body weight. The more these patients lose, the more likely their body is breaking down muscle. “I watch them very carefully,” he told me. The impacts of losing muscle may go beyond losing just strength. Muscle cells are major consumers of energy; they influence insulin sensitivity and absorb some 80 percent of the glucose flooding into blood after a meal. Extreme loss might alter these metabolic functions of muscle too.

    Exactly how all of this will affect people on Wegovy and Zepbound, which are still relatively novel obesity drugs, is too early to say. (You may have heard these same two drugs referred to as Ozempic and Mounjaro, respectively, which are their names when sold for diabetes.) These drugs cause a proportion of muscle loss higher than diet and exercise alone, though roughly on par with bariatric surgery. Lifestyle changes can blunt the loss, but pharmaceutical companies are on the hunt for new drug combinations that could build muscle while burning fat.

    The arrival of powerful weight-loss drugs has moved the field beyond simple weight loss, Melanie Haines, an endocrinologist at Massachusetts General Hospital, told me. That challenge is largely solved. Instead of fixating on the number of pounds lost, researchers, doctors, and ultimately patients can focus on where those pounds are coming from.

    Doctors currently offer two pieces of standard and unsurprising advice to protect people taking obesity drugs against muscle loss: Eat a high-protein diet, and do resistance training. These recommendations are perfectly logical, but their effectiveness against these drugs specifically is unclear, John Jakicic, a professor of physical activity and weight management at the University of Kansas Medical Center, told me. He is now surveying patients to understand their real-world behavior on these drugs.

    Fatigue, for example, is a common side effect. “When you’re tired, and you’re fatigued, do you really feel like exercising?” he said. Haines wonders the same about eating enough protein. The drugs are so good at suppressing appetite, she said, that some people might not be able to stomach enough food to get adequate protein. (Food companies have started pitching high-protein snacks and shakes to people on obesity drugs.)

    Read: The Ozempic plateau

    If patients stop taking Wegovy and Zepbound—and about half of patients do stop within a year, at least in real-world studies of people taking this class of drugs for diabetes—the weight regained comes back as fat more than muscle, says Tom Yates, a physical-activity professor at the University of Leicester. Muscle mass tends not to entirely recover. It’s “almost as if you’re better off staying where you are than going through cycles of weight loss,” he told me.

    Yet, he pointed out, the U.K. recommends Wegovy for a maximum of two years. In the U.S., patients who can’t afford the steep out-of-pocket price have been forced to stop when insurance companies abruptly cut off coverage or a manufacturer’s discount coupon expires. These policies are likely to trigger cycles of weight loss and gain that lead, ultimately, to net muscle loss.

    Meanwhile, drug companies are already thinking about the next generation of weight-loss therapies. “Wouldn’t it be great to have another mechanism that’s moving away from just appetite regulation?” Haines said. Companies are testing ways to preserve—perhaps even enhance—muscle during weight loss by combining Wegovy or Zepbound with a second muscle-boosting drug. Such a combination could, in theory, allow patients to lose fat and gain muscle at the same time.

    Years ago, scientists first became interested in potential muscle-enhancing drugs that mimic mutations found in certain breeds of almost comically ripped dogs and cattle. At the time, they hoped to treat muscle-wasting diseases. The drugs never quite worked for that purpose, but the trial for one such drug, an antibody called bimagrumab, found that patients also lost fat in addition to gaining lean mass. A start-up acquired the drug and began testing it for weight loss in combination with semaglutide, the active ingredient in Wegovy, or Ozempic. And last year, Eli Lilly, the maker of Zepbound, snapped up that company for up to $1.9 billion—in hopes of making its own combination therapy.

    Read: Are you sure you want an Ozempic pill?

    Pairing bimagrumab with an existing obesity drug could potentially maximize the weight loss from both. Losing weight tends to get harder over time; as you lose muscle, your body burns fewer calories. A drug that minimizes that muscle loss—or even flips it into muscle gain—could help patients boost the amount of energy their body expends, while Wegovy or Zepbound suppresses calories consumed. The mechanisms of how this might actually work in the body still need to be understood, though. Previous studies of bimagrumab found that patients grew more muscle, but they didn’t necessarily become faster or stronger. Haines, who is planning a small study of her own with bimagrumab, is most interested in how the combination affects not the structural but the metabolic functions of muscle.

    Bimagrumab is the furthest along of several drugs that tinker with the same pathway for muscle growth. The biotech company Regeneron recently published promising data on two of its muscle-enhancing antibodies paired with semaglutide in primates; a trial in humans is due to begin later this year. The start-up Scholar Rock is testing another antibody called apitegromab. Other companies are interested in combining the obesity drugs with different potential muscle boosters that work by mimicking certain hormones such as apelin or testosterone. If they succeed, the next generation of drugs could help sculpt a more muscular body, not just a smaller one. Eating less can only do so much to better your health.



    Sarah Zhang

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  • Are You Sure You Want an Ozempic Pill?

    Are You Sure You Want an Ozempic Pill?

    Within the first five seconds of a recent Ozempic commercial, a sky-blue injector pen tumbles toward the viewer, encircled by a big red O. Obesity drugs have become so closely associated with injections that the two are virtually synonymous. Like Ozempic, whose name is now a catchall term for obesity drugs, Wegovy and Zepbound come packaged in Sharpie-like injection pens that patients self-administer once a week. Patients “don’t come in asking for Wegovy,” Laura Davisson, a professor of medical weight management at West Virginia University, told me. “They come in asking for one of ‘those injectables.’”

    Needles are the present, but supposedly not the future. Nobody really likes injections, and taking a pill would be far easier. In the frenzy over obesity drugs, a class known as GLP-1 agonists, drugmakers have raced to create them in pill form, and Wall Street investors are hungry at the prospect. Earlier this year, Pfizer’s CEO, Albert Bourla, estimated that obesity pills could be worth $30 billion, or a third of the total obesity-drug market. Because people have a “preference” for pills, he said at a conference, they will be what ultimately “unlocks the market” for obesity medications. By one count, at least 32 oral GLP-1 drugs, from many different companies, are in the works.

    But a future dominated by obesity pills is hardly certain. So far, the only oral GLP-1 that exists is a pill for diabetes called Rybelsus. Like Ozempic and Wegovy, its active ingredient is a compound called semaglutide, but the shots come in far more powerful doses, making it possible to lose even more weight. Developing oral obesity drugs that are as tolerable and effective as their injectable counterparts has so far been a challenge. Earlier this month, Pfizer stopped testing one of its pill candidates, citing concerns about side effects and patient adherence. Even when pills do come to market, doctors told me, there’s no guarantee that people will flock to them.

    That drugmakers view the injectable nature of GLP-1s as one of their biggest flaws is no surprise. Getting a shot is a broadly despised experience, something people generally tolerate rather than choose. Children get stickers for enduring immunizations; adults who get vaccinated do so only because they must (and they are often rewarded with stickers too). The CDC estimates that one in four adults, and two out of three children, have strong fears about needles. “Some people hate needles, plain and simple,” Ted Kyle, an obesity-policy expert, told me.

    But not all needles are made equal. Wegovy and Zepbound are injected subcutaneously, or just under the skin. Relative to COVID or flu shots, which are jabbed into muscle, they don’t cause much discomfort. “I’ve been really surprised at how receptive my patients have been to using injectable medications,” Davisson said. Other doctors I spoke with agreed. “More patients than you would expect really don’t mind injectables,” because they’re easy and relatively painless to administer, Katherine Saunders, a clinical-medicine professor at Weill Cornell Medicine, told me.

    The unobtrusive dosing schedule of the injectables adds to their appeal. Wegovy and Zepbound are administered once weekly, unlike many of the pills in development, which are meant to be taken once or more daily. That can be a hassle, especially if they have to be taken at the same time every day, or if they come with restrictions on eating or drinking. “For some people, it’s easier to take an injection and forget about it for a week” than to remember to take a pill every day, Eduardo Grunvald, an obesity-medicine physician at UC San Diego Health, told me. Assuming pills are preferable to shots is a “knee-jerk reaction,” he added.

    Despite the unexpected upsides of the shots, they’re far from perfect. Making injectable pens is generally more expensive than pills and requires a lot of hardware, including the pen casing, cap, and needle cover. On top of that, the injectable obesity drugs must be refrigerated before they are first used, adding to storage and production costs. Pills are generally shelf-stable and don’t require much packaging beyond a child-proof bottle. Saunders predicts they would be less expensive and less prone to shortages that have plagued Wegovy.

    Still, creating an obesity pill isn’t as simple as packaging the same drugs in capsule form. Drugmakers have already run into a number of issues. Absorption is a big one: Because pills pass through the stomach before entering the bloodstream, they must be able to withstand a large degree of degradation. One way to get these drugs to lead to greater weight loss is to increase the dose. While the highest dose of Wegovy is 2.4 milligrams, Rybelsus maxes out at 14 milligrams.

    Hiking up the dose seems to work, though doing so could have consequences beyond weight loss. All GLP-1 drugs come with a range of unpleasant side effects involving the gastrointestinal system, and patients report nausea at similar rates in Rybelsus and Ozempic, according to the FDA. But this may differ in practice, as other doctors have noted. Saunders said that her patients on oral semaglutide report more nausea than those using injectables. Regardless, newer oral medications may have even more distinct differences, as drugmakers race to create more potent pills. In Pfizer’s discontinued trial of danuglipron, nausea rates reached up to 73 percent.

    Drugmakers also skirt the issue of degradation by pursuing sturdier drugs. The problem with semaglutide is that it’s a peptide—essentially a small protein—precisely the kind of molecule that the stomach excels at digesting. Some new drugs in the pipeline are so-called non-peptide small molecules, which are sturdier but still have the same biological effect. Orforglipron, a pill that Eli Lilly is testing, falls into this category, as does danuglipron, the drug responsible for Pfizer’s recent setbacks. Small-molecule drugs have the added benefit of being cheaper to produce at scale than peptides, Kyle, the obesity-policy expert, added.

    Another pesky problem with oral drugs is that they tend to come with strict dosing requirements. People on Rybelsus, for example, are instructed to take it 30 minutes before eating or drinking anything and can drink only four ounces of plain water along with it, because otherwise absorption could be compromised. “It can be a nuisance,” Grunvald said. Similarly bothersome instructions likely played a part in the drop-out rates reaching more than 50 percent in Pfizer’s recently discontinued trial: Danuglipron had to be taken twice daily. “A lot of people found it not worth the trouble,” Kyle said, noting that Pfizer is still pursuing a once-daily version of the same drug. A recent review of GLP-1 drugs showed that, compared with the injectable form, oral semaglutide is associated with lower rates of side-effect reporting but higher discontinuation rates, potentially reflecting its bothersome dosage requirements.

    Despite these hurdles, it seems inevitable that obesity-drug pills will eventually become available. Novo Nordisk is expected to file for FDA approval for its high-dose semaglutide obesity pill this year; Pfizer is forging ahead with a once-daily version of danuglipron, with more data expected “in the first half of 2024,” a spokesperson told me. A report from BMO Equity Research published in September predicted that oral formulations could be approved “by the late 2020s.” The biggest upside to pills may not be that they are pills but that they will, eventually, be cheaper than injectables—and cost is among the biggest impediments to more people taking obesity drugs.

    Whether they’ll replace injectables outright is far from certain. “It will come down to patient preference,” Grunvald said. Most likely, pills and injections will coexist to meet different needs, and perhaps even be used together to treat individual patients. In the so-called phased approach, obesity treatment could start with more expensive and powerful injectable drugs, then transition to less potent but cheaper orals for the long term. Eli Lilly, for one, sees its oral candidate, orforglipron, as a potential weight-loss-maintenance drug.

    There is so much competition in the obesity-drug space that future medications may take more unexpected forms. Amgen is studying a once-monthly injection; Novo Nordisk is developing a hydrogel form of semaglutide that would need to be taken only three times a year. If the future of obesity drugs will come down to what patients prefer, then the more options, the better.

    Yasmin Tayag

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  • The Cold-Medication Racket

    The Cold-Medication Racket

    You wake up with a stuffy nose, so you head to the pharmacy, where a plethora of options awaits in the cold-and-flu aisle. Ah, how lucky you are to live in 21st-century America. There’s Sudafed PE, which promises “maximum-strength sinus pressure and nasal congestion relief.” Sounds great. Or why not grab DayQuil in case other symptoms show up, or Tylenol Cold + Flu Severe should whatever it is get really bad? Could you have allergies instead? Good thing you can get Benadryl Allergy Plus Congestion, too.

    Unfortunately for you and me and everyone else in this country, the decongestant in all of these pills and syrups is entirely ineffective. The brand names might be different, but the active ingredient aimed at congestion is the same: phenylephrine. Roughly two decades ago, oral phenylephrine began proliferating on pharmacy shelves despite mounting—and now damning—evidence that the drug simply does not work.

    “It has been an open secret among pharmacists,” says Randy Hatton, a pharmacy professor at the University of Florida, who filed a citizen petition in 2007 and again in 2015 asking the FDA to reevaluate phenylephrine. This week, an advisory panel to the FDA voted 16–0 that the drug is ineffective orally, which could pave the way for the agency to finally pull the drug.

    If so, the impact would be huge. Phenylephrine is combined with fever reducers, cough suppressants, or antihistamines in many popular multidrug products such as the aforementioned DayQuil. Americans collectively shell out $1.763 billion a year for cold and allergy meds with phenylephrine, according to the FDA, which also calls the number a likely underestimate. That’s a lot of money for a decongestant that, again, does not work.

    Over-the-counter oral decongestants weren’t always this bad. But in the early 2000s, states began restricting access to pseudoephedrine—a different drug that actually is effective against congestion—because it could be used to make meth; the Combat Methamphetamine Epidemic Act, signed in 2006, took the restrictions national. You can still buy real-deal Sudafed containing pseudoephedrine, but you have to show an ID and sign a logbook. Meanwhile, manufacturers filled over-the-counter shelves with phenylephrine replacements such as Sudafed PE. The PE is for phenylephrine, but you would be forgiven for not noticing the different name.

    “Thet switch from pseudoephedrine to phenylephrine was a big mistake,” says Ronald Eccles, who ran the Common Cold Unit at Cardiff University until his retirement. Eccles was critical of the switch back in 2006. The evidence, he wrote at the time, was already pointing to phenylephrine as a lousy oral drug.

    Problems started showing up quickly. Hatton, who was then a co-director of the University of Florida Drug Information Center, started getting a flurry of questions about phenylephrine: Does it work? What’s the right dose? Because my patients are complaining that it’s not doing anything. He decided to investigate, and he went deep. Hatton filed a Freedom of Information Act request for the data behind FDA’s initial evaluation of the drug in 1976. He soon found himself searching through a banker’s box of records, looking for studies whose raw data he and a postdoctoral resident typed up by hand to reanalyze. The 14 studies the FDA had considered at the time had mixed results. Five of the positive ones were all conducted at the same research center, whose results looked better than everyone else’s. Hutton’s team thought that was suspicious. If you excluded those studies, the drug no longer looked effective at its usual dose.

    All told, the case for phenylephrine was not great, but the case against was no slam dunk either. When Hatton and colleagues at the University of Florida, including Leslie Hendeles, filed a citizen petition, they asked the agency to increase the maximum dose to something that could be more effective. They did not ask to pull the drug entirely.

    There was more damning evidence to come, though. The petition led to a first FDA advisory committee meeting, in 2007, where scientists from a pharmaceutical company named Schering-Plough, which later became Merck, presented brand-new data. The company had begun studying the drug, Hatton and Hendeles recalled, because it was interested in replacing the pseudoepinephrine in its allergy drug Claritin-D. But these industry scientists did not come to defend phenylephrine. Instead, they dismantled the very foundation of the drug’s supposed efficacy.

    They showed that almost no phenylephrine reaches the nasal passages, where it theoretically could reduce congestion and swelling by causing blood vessels to constrict. When taken orally, most of it gets destroyed in the gut; only 1 percent is active in the bloodstream. This seemed to be borne out by what people experienced when they took the drug—which was nothing. The scientists presented two more studies that found phenylephrine to be no better than placebo in people congested because of pollen allergies.

    These studies, the FDA later wrote, were “remarkable,” changing the way the agency thought about how oral phenylephrine works in the body. But experts still weren’t ready to write the drug off entirely. The 2007 meeting ended with the advisory committee asking for data from higher doses.

    The story for phenylephrine only got worse from there. In hopes of making an effective product, Merck went to study higher doses in two randomized clinical trials published in 2015 and 2016. “We went double, triple, quadruple—showed no benefit,” Eli Meltzer, an allergist who helped conduct the trials for Merck, said at the FDA-advisory-panel meeting this week. In other words, not only is phenylephrine ineffective at the labeled dosage of 10 milligrams every four hours, it is not even effective at four times that dose. These data prompted Hatton and Hendeles to file a second citizen petition and helped prompt this week’s advisory meeting. This time, the panel didn’t need any more data. “We’re kind of beating a dead horse … This is a done deal as far as I’m concerned. It doesn’t work,” one committee member, Paul Pisarik, said at the meeting. The advisory’s 16–0 vote is not binding, though, so it’s still up to the FDA to decide what to do about phenylephrine.

    In any case, phenylephrine is not the only cold-and-flu drug with questionable effectiveness in its approved form. The common cough drugs guaifenesin and dextromethorphan have both come under fire. But we lack the robust clinical-trial data to draw a definitive conclusion on those one way or the other. “What really helped our case is the fact that Merck funded those studies,” Hatton says. And that Merck let its scientists publish them. Failed studies from drug companies usually don’t see the light of day because they present few incentives for publication. Changing the consensus on phenylephrine took an extraordinary set of circumstances.

    It also required two dogged guys who have now been at this work for nearly two decades. “We’re just a couple of older professors from the University of Florida trying to do what’s best for society,” Hatton told me. When I asked whether they would be tackling other cold medications, he demurred: “I don’t know if either one of us has another 20 years in us.” He would instead like to see public funding for trials like Merck’s to reevaluate other over-the-counter drugs.

    There are other effective decongestants on pharmacy shelves. Even though phenylephrine does not work in pill form, “phenylephrine is very effective if you spray it into the nose,” Hendeles says. Neo-Synephrine is one such phenylephrine spray. Other nasal sprays containing other decongestants, such as Afrin, are also effective. But the only other common oral decongestant is pseudoephedrine, which requires that extra step of asking the pharmacist.
    Restricting pseudoephedrine has not  curbed the meth epidemic, either. Meth-related overdoses are skyrocketing, after Mexican drug rings perfected a newer, cheap way to make methamphetamine without using pseudoephedrine at all. This actually effective drug still remains behind the counter, while ineffective ones fill the shelves.

    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

    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.

    Yasmin Tayag

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