In the inner circles of obesity specialists, they call it the Hunger Games. Every day, the drama of Wegovy, Ozempic, and Mounjaro plays out on the cultural arena—the stunning weight-loss results, the equally stunning price tags, the divide of patients who can get them versus those who can’t (to say nothing of those people who score and don’t actually need them). The stakes are high. Against the backdrop of an obesity epidemic affecting 42 percent of Americans and half of all Black adults, you’ve got shortages of the drugs, scammers pushing fakes, shamers bitching about “Ozempic face”—and in the fevered heat of it all, the hunger itself…which (what?) is gone.
Maybe you’re watching this battle of the body slimmers from the sidelines. Maybe you’re busy playing the “Is she or isn’t she?” game. Or maybe you’re curious about what it could mean for you or someone you love, and whether these meds are too good to be true or truly safe in the long run. Here’s the latest intel.
The key players
No one quite noticed when the FDA approved Ozempic, made by Danish drugmaker Novo Nordisk, in December 2017. But it soon became clear that the so-called GLP-1 drug, a hormone mimicker to treat diabetes, also seemed to make patients thinner. “Some patients lost 30 percent of their body weight,” says Howard Rosen, MD, who shared an endocrinology practice in Kansas City, Missouri, at the time. “They’d say, ‘It’s the strangest thing, but I don’t think about food all the time any more.’” For the next few years, some doctors prescribed it off-label to people who didn’t have diabetes, while Novo Nordisk studied the same drug (semaglutide) at a higher dose specifically for weight loss. That new drug, Wevogy, was approved by the FDA on June 4, 2021. In trials, patients who took it for two years lost an average of 15.2 percent of their body weight, while over a third dropped at least 20 percent, nearly double any other weight-loss medication on the market. And that’s just what you can see on the scale. In August, Novo Nordisk announced that the drug also reduced the risk of heart attack, stroke, and death in those with cardiovascular disease by 20 percent—findings that await publication in a peer-reviewed journal but are dazzling in their promise. That news was followed by a study showing the drug reduced symptoms for people with heart failure. It may even help with addiction, according to other research and anecdotal reports.
More From Oprah Daily
Completing the Big Three is tirzepatide (Mounjaro), by Eli Lilly, which impersonates two hunger-regulating hormones: GLP-1 and GIP. Currently approved only for diabetes, it’s following a similar track as semaglutide and is under FDA review for the treatment of obesity, with a decision expected by the end of the year. So far, it looks even more potent: On average, over 72 weeks, people at the highest doses lost 20.9 percent of their body weight.
How they work
What’s important to know is that the body has its own biological algorithm for determining your weight, and it’s calibrated by pathways of hormones that do things like make us hungry and store adipose tissue. In people with obesity, which is a chronic multi-metabolic and hormonal disease, as defined by the American Medical Association, these pathways are in some way dysfunctional or impaired. Back in the 1990s, there was a flurry of excitement around the discovery of the appetite hormones leptin and ghrelin, but those have yet to lead to successful drugs. Instead, scientists hit the jackpot when they tinkered with another player in the system called GLP-1, a hormone of interest since the 1980s because it’s secreted after you eat to help push insulin production, which regulates blood sugar levels.
“I must say, if you’d told me we were gonna create some gut hormones that would be the solution to weight problems, I would have said good luck with that,” says Thomas Wadden, PhD, professor of psychology in the department of psychiatry at the Perelman School of Medicine at the University of Pennsylvania, who was an investigator on the Wegovy trials. Why the early skepticism? “GLP-1 has such a short half-life,” Wadden explains. “You feel full for two to three minutes after you eat your dinner, but then it fades, and 15, 20 minutes later, you’re thinking, That’s a good-looking piece of cake.” The beauty of semaglutide (the drug in Ozempic and Wegovy), which mimics GLP-1, is that it has a half-life of seven days. Tirzepatide (Mounjaro) lasts for five.
It’s not entirely clear how these drugs make you lose weight. While they seem to delay gastric emptying and keep you full for longer, experts say their biggest effect is in the brain. They “sneak in,” says Randy Seeley, PhD, director of the Michigan Nutrition Obesity Research Center at the University of Michigan. “And it has been somewhat mysterious why they land in the places they can. But they include areas that control your food intake.”
Seeley clarifies that people with obesity don’t lack GLP-1. “These drugs are not fixing what’s broken,” he says. We know that the natural GLP-1 hormones in your body are elevated after a large meal. But the drugs give you five times what you’d have after eating a Thanksgiving dinner. And the jolt is like giving the whole hormone pathway a chiropractic adjustment, affecting the hunger and satiety signals down the line. “This is a system that when we bang on it in the correct way, we get an enormous benefit.”
Another way to put it is that the drugs trick your body to lower your weight set point, or “defended fat mass,” as it’s now being called by experts like Ania Jastreboff, MD, Phd, director of the Yale Obesity Research Center and lead author on some of the Mounjaro studies. This is the weight your body thinks is normal, and when you try to nudge it downward by cutting calories, you get ravenous, besieged by cravings, and your metabolism slows down as your hormone systems fight back because they think you’re starving.
Jastreboff and other experts believe that these medications may lower that defended fat mass or set point. The result, as Rosen observed in his patients, is silence. The old “food noise,” that constant Muzak playing in the brain whether you’re talking on the phone or writing code (What am I going to have for lunch, for dinner, right now, yes…no! not the chips), is simply turned off. “My patients struggle with this their entire lives,” Jastreboff says. “It consumes so much thought. Then you provide them with something that targets biology, and suddenly they have all this space to think about all the other things in life.”
How to get (and pay for) them
Technically, to get an Rx for Wegovy, you need to have at least a BMI of 30—or 27 with a weight-related ailment; Ozempic and Mounjaro require a diagnosis of type 2 diabetes. But high demand, partly caused by people taking these drugs who don’t need them, has caused supply problems. As Novo Nordisk (shortage updates here) and Eli Lilly (which expects intermittent back orders of some doses through September) urgently try to solve that problem, most people face another. These drugs are expensive—Wegovy’s list price is $1,349.02 a month—and many private insurers, employers, and government plans won’t pay for it. Nor will they often cover Ozempic and Mounjaro, around $1,000 a month, when used off-label to treat obesity.
Medicare is actually prohibited by a 2003 law from covering any drugs specifically for weight loss—born partly out of skepticism that people will use them for cosmetic reasons. There is a push from the pharmaceutical companies to pass a bill in Congress, called the Treat and Reduce Obesity Act, that would change Medicare’s mandate; meanwhile, various behind-the-scenes analyses try to estimate the exorbitant costs of coverage and the potentially larger savings from preventing other diseases by treating obesity, but it will take real-time data to determine where it nets out. All to say, it’s gonna be a while.
Kimberly Gudzune, MD, medical director of the American Board of Obesity Medicine, says that in her clinical practice, she’s had some success getting coverage for patients with weight-related conditions like prediabetes, nonalcoholic fatty liver disease, polycystic ovary syndrome, or cardiovascular disease, but it can be a lengthy process that requires submitting appeals and reviews. She recommends that you talk to the HR or benefits folks at your job, as often it’s more up to your employer than just the health insurer. “Some companies are not aware that they are not covering these treatments and that their employees want them,” she says. Or, if you’re willing and able to travel, according to a report by the health policy research nonprofit KFF, Ozempic costs $936 a month in the U.S. but only $147 in Canada. You could probably even beat the price here by flying to France every four weeks to nab your supply for $83—and not even notice the patisseries.
One place not to get these drugs is at an online site—unless you find a legitimate telehealth company like Ro, Calibrate, or Knownwell. Many of the offers that pop up are scams. The FDA warns that some products sold as semaglutide may be salt formulations like semaglutide sodium and semaglutide acetate, which haven’t been shown to be safe or effective. The agency also says it has “received adverse event reports after patients used compounded semaglutide.” Novo Nordisk notes that it doesn’t sell either Wegovy or semaglutide for compounding with other products; nor does the FDA monitor the pharmacies that make them.
Compliance and commitment
Until there’s a daily tablet (in the works), you have to take Wegovy by weekly DIY injections. The same is true for the diabetes med Mounjaro, but you can get a pill version of Ozempic called Rybelsus. You also have to go on Wegovy for life if you want to keep the weight off, which brings up the larger conversation of obesity being a chronic disease. GLP-1 drugs are not designed to shrink you into your college reunion dress; instead they’re used like medication for hypertension. Quit Wegovy and in about a year, you’re likely to regain two thirds of the weight you lost. And as with your blood pressure med, if your GLP-1 becomes ineffective over time, you may need to switch to another treatment. No matter what you do, experts stress that a nutritious diet (not to be confused with dieting) and physical activity are still key to controlling your weight and staying healthy.
What about side effects?
Kristin Lloyd, PhD, a psychotherapist and coach for patients who’ve had weight loss surgery through her company Bariatric Mindset, is concerned that the social stigma against men and women in larger bodies is causing desperation for the drugs. “I’ve seen people on Facebook: ‘Just gimme the shot!’” says Lloyd. She knows the feeling, having lost 200 pounds through bariatric surgery herself 10 years ago after trying everything else. “When they were thinking of pulling fen-phen, I said, ‘I don’t care. I just need to be thin,’” she recalls of the older diet drug. “I cared more about that than if I were to have a heart attack.” Fen-phen, a combo drug of phentermine and fenfluramine, bolted out of the gate as a potential blockbuster in the 1990s. It was only when millions of people went on it that rare side effects like pulmonary hypertension and heart valve damage emerged, and in some cases, proved deadly.
In contrast, GLP-1 has been used safely to treat type 2 diabetes for more than 15 years. But Wegovy is a higher dose, and it’s not for diabetes. What happens if you take it for a decade or two? And could some hidden danger emerge if it becomes accessible to people en masse? “As someone who has studied medications for over 13 years, I’d say dosing probably matters, and who’s getting it matters,” says Stacie Dusetzina, PhD, professor of health policy at Vanderbilt University School of Medicine. “We often see that trials exclude many people who would otherwise look like the population who takes the drugs—people with certain comorbidities or certain age groups. And when we then start to use these drugs in a population, sometimes things happen that we aren’t expecting. So I think you can be excited, but it’s also worth being cautious.”
For example, in the Wegovy trials, according to investigator Wadden, they screened out anyone with recent major depression or suicidal ideation to see whether it caused either. “And it doesn’t appear to,” he says, “but if you give the drug to people who have those problems in advance, it could be a different answer.” He’s also concerned about at-risk patients over 65 due to the likely loss of lean muscle mass and possibly bone mineral density from the rapid weight drop. “It just hasn’t been studied yet to see what these drugs do in these patients.”
Another question that has come up involves gastroparesis, also called delayed gastric emptying, which slows or stops food from moving out of the stomach. The companies have been clear that the drugs commonly cause nausea, constipation, and diarrhea, as well as vomiting (which 24 percent of Wegovy patients reported in one study), all side effects that usually go away after a month or two, while rarer ones include gallbladder problems and pancreatitis. But Jaclyn Bjorklund, a woman in Louisiana, claims she suffered severe vomiting and pain that required hospitalization due to gastroparesis after taking Ozempic and Mounjaro. In August, she sued their makers, alleging they “downplayed the severity of the gastrointestinal events” and that they didn’t “adequately warn of all possible adverse side effects” including the increased risk of gastroparesis.
Asked for comment on the lawsuit, spokespeople for both drug companies didn’t respond directly but stressed that they prioritized patient safety and worked carefully to ensure the labels contained accurate information. “GLP-1’s are known to cause a delay in gastric emptying, as noted in the label of each of our GLP-1 RA medications,” said Ambre James-Brown of Novo Nordisk. “Symptoms of delayed gastric emptying, nausea, and vomiting are listed as side effects.” Courtney Kasinger responded for Eli Lilly that “Mounjaro’s label states that use of Mounjaro may be associated with gastrointestinal adverse reactions, some of which can be severe. Its label also states that Mounjaro has not been studied in patients with severe gastrointestinal disease and is therefore not recommended in these patients.” Neither company has filed a formal response to the lawsuit.
Bottom line: These drugs aren’t for everyone
Despite her enthusiasm for the GLP-1 drugs, Fatima Cody Stanford, MD, associate professor of medicine and pediatrics at Harvard Medical School and an obesity medicine physician scientist at Massachusetts General Hospital, says they don’t always work. “Everyone is not a responder to these medications,” she explains. “And some people respond, but their side effects are so profound that it wouldn’t be something you’d continue them on, because they’re sick. I don’t believe that they’re a panacea by any stretch of the imagination.”
To her point, in the Wegovy trials demonstrating the 15 percent average loss, one out of five people didn’t reach 5 percent of their body weight, and a few gained pounds. Also, many people don’t want to take the drugs because they’re injections or they have to go on them long-term. If they’re not for you, there are other options. For eligible patients with severe obesity, bariatric surgery actually has a lot of similarities to the GLP-1 drugs—including effectiveness. On average, people who’ve had it lost 28.4 percent of their body weight after seven years, according to a long-term study funded by the National Institute of Diabetes and Digestive and Kidney Diseases. It seems obvious that downsizing your stomach would mean eating less food, but if that’s all it is, “you should be more hungry, right?” says Seeley, “and that’s not what happens. The surgery is changing the way your GI tract is talking to the rest of your body, and that changes the set point.” After 10 years, a lot of patients do start to gain the weight back, says Melanie Jay, MD, who practices obesity medicine at the VA New York Harbor, and is associate professor of medicine and population health at the NYU Grossman School of Medicine. “It just means we might have to add something.” Now many doctors are putting these patients on the new medications to maintain their loss.
But older anti-obesity medications can make a difference, too—and sometimes they’re the best choice. Contrave is a combination of naltrexone and bupropion, two drugs that are also prescribed for substance abuse and smoking cessation, respectively. “If someone has an addictive personality, it’s theoretically working on that pathway,” says Jay. It can also be helpful for people with food cravings or emotional eating, per the American Board of Obesity Medicine’s Gudzune, who is also an associate professor of medicine at Johns Hopkins University.
The most effective older drug by the numbers is Qsymia (phentermine and topiramate), which has been available since 2012. It causes an average loss of about 10 percent, but a good responder could find themselves in the range of Wegovy. “In my experience, this has been most helpful for people who have a sweet tooth,” says Gudzune. But she also stresses that there’s no “one size fits all” strategy when treating obesity. Sometimes her patients do well on hydrogel, a cellulose-based pill that’s considered a medical device because it absorbs water and expands in your stomach. “I like to think of it as eating a bunch of cucumbers before a meal,” she says.
The road ahead
In the next year or two, several more hormone-based options are likely to drop. With the success of the GLP-1 drugs, there’s a vigorous pipeline of new meds in the making, like Novo Nordisk’s Amycretin and CagriSema, which also target another hunger hormone called amylin. Already there’s been buzz about Eli Lilly’s newcomer retatrutide—not just one or two, but three hormone mimickers combined, giving it the irresistible nickname “Triple G.” It’s still being studied, but in one trial, at only 48 weeks, it’s leaping ahead of the first GLP-1’s and seems to be particularly effective in women, who dropped, on average, 28.5 percent of their body weight. “I don’t think it’s inconceivable that we could have weight loss of 35 percent with these drugs,” says Jastreboff, lead author of one of the trials.
It remains to be seen how numbers like this will reshape the obesity epidemic—and the deep well of shame and stigma over body size in our culture. A. Janet Tomiyama, PhD, director of UCLA’s Dieting, Stress, and Health research laboratory, is still figuring out where she comes down on the whole GLP phenomenon. “I can see how a medication like this can feel really scary to heavier people, who already feel under siege by a medical profession that they perceive is trying to eradicate everyone that looks like them,” she says. “But I’ve also heard from patients who wanted to scream every time their physician told them to try a new diet. They’d been on every diet. For people like that, these medications feel like a breath of fresh air because their physician is saying, ‘Let’s treat this medically, just like any other medical condition, and this is going to actually work.’”
Any content published by Oprah Daily is for informational purposes only and does not constitute medical advice, diagnosis, or treatment. It should not be regarded as a substitute for professional guidance from your healthcare provider.
Many obesity specialists work with pharmaceutical companies in hopes of advancing treatment. Kimberly Gudzune, Randy Seeley, Fatima Cody Stanford, Thomas Wadden, Ania Jastreboff have all done research and/or consulted with either Novo Nordisk or Eli Lilly or both.
In a groundbreaking conversation with Oprah, Oprah Daily Insiders, and obesity specialists Fatima Cody Stanford, MD, Melanie Jay, MD, Sima Sistani (CEO of WeightWatchers), and psychologist Rachel Goldman, PhD, we debunk long-standing myths about weight. Become an Oprah Daily Insider now to access this conversation and the full “The Life You Want” Class library.
link