A So-Called Game-Changing Weight Loss Drug Is Here — So What Happens Next?

A So-Called Game-Changing Weight Loss Drug Is Here — So What Happens Next?

In early February this year, on her YouTube channel “The Hangry Woman,” Mila Clarke Buckley shared her positive experiences taking Ozempic, an antidiabetic medication taken via weekly subcutaneous injection that was first approved by the U.S. Food and Drug Administration in 2017.

After two months on it, she recounted, her too-high average blood sugar level (the defining characteristic of diabetes) had steadily declined, her constant and intrusive cravings for food had gone away, and she began to lose weight consistently. But she also, like many users, experienced a week or so long bout of gastrointestinal symptoms like nausea and constipation once she moved up to a slightly higher dose, which was almost enough to make her stop taking the drug.

Buckley stuck through the initial turbulence, though, and in a six-month update video, she called it a wonder drug that finally helped her lower her blood sugar — a years-long frustration that she had discussed in earlier videos. In the comments of both her videos were curious onlookers and Ozempic users who backed up her claims of newfound success in managing their diabetes and losing weight.

“After I started taking it, it was almost immediate. I dropped like eight pounds within two months doing nothing differently. So for me, this was awesome, because I’ve always had trouble with this,” Buckley, an author, speaker, and blogger who largely talks about her experiences with diabetes on her channel, told Gizmodo over the phone. “But it’s really interesting that it’s working in this way. Both for weight loss, which is always something that I wanted for myself — my doctor’s never said that I have to lose weight — and then to also have it be something that was helping with my diabetes management.” 

Buckley’s review would soon be relevant to an even greater number of people than the 34 million Americans currently thought to have diabetes. Days after her latest video, Ozempic’s makers, Novo Nordisk, obtained approval from the Food and Drug Administration to sell a new, higher dose version of the drug called Wegovy — one explicitly meant to help people with obesity, long since (and more controversially as of late) defined as having a body mass index over 30, lose weight.

Scientists and doctors have praised the active ingredient in both drugs, known as semaglutide. They’re gone as far as to call it a “game-changer” that could usher in a new era of obesity treatment, both because it’s helped people lose considerably more weight than past remedies and because it seems to work on several aspects of our biology linked to obesity, like our metabolism.

Yet, there remain many hurdles standing in the way of its potential, from whether insurance carriers will even cover it to the unknown long-term risks of a treatment that’s likely to be needed for a lifetime. Additionally, some activists and experts question the inherent value of antiobesity drugs and worry about the floodgates of medical fatshaming and pharmaceutical profiteering that Wegovy’s approval will open up.

Semaglutide belongs to a class of drugs known as GLP-1 agonists, GLP-1 standing for the hormone glucagon-like peptide 1, which helps regulate many bodily functions. One of these roles, according to Donna Ryan, a longtime obesity researcher and professor emerita at the Pennington Biomedical Research Centre in Louisiana, is being part of the natural balancing act that is digestion and metabolism.

In the pancreas, for instance, it stimulates insulin production when blood sugar spikes, which stabilises blood sugar levels. In the stomach, it slows down the emptying of food and decreases stomach acid production, leading to the sensation of fullness. And in the brain, it tamps down our appetite and cravings between meals. Because GLP-1 drugs resemble GLP-1 molecularly, they essentially boost the body’s supply of it; but they also stick around in the body for longer.

“The drugs differ from native GLP-1 in that they have modifications to make them last longer — native GLP-1 only has a half life of 1-2 minutes, while Ozempic has an over 150 hour half life,” Ryan, who has received consulting fees and other financial payments from Novo Norodisk, told Gizmodo in an email.

By amplifying GLP-1, you can help rebalance the biological process that’s gone awry in most people with diabetes, specifically when it comes to insulin. (People with type 1 diabetes no longer produce insulin, but those with type 2 and latent autoimmune diabetes can continue to produce it until their condition progressively worsens.) And because some of these metabolic problems arise in people with obesity, itself a suspected risk factor for type 2 diabetes, the hope is GLP-1 drugs will repair these problems found in people with obesity, too.

What’s made semaglutide so tantalising to researchers isn’t just the biology behind it but the actual results. Earlier this year, Novo Norodisk published the first of several double-blinded, placebo-controlled, and randomised large trials testing out semaglutide for people with obesity. Compared to those on placebo, with both groups given standard counseling on dieting and exercise, people taking the drug — injected once weekly just under the skin — lost substantial amounts of weight. In one of the pivotal trials reviewed for FDA approval, the average weight loss from a person’s baseline was around 15% over 68 weeks.

Like Ozempic, Wegovy is taken via a weekly subcutaneous injection in gradually increasing doses to help users adjust. It’s formally approved for people with obesity or people with a BMI over 27 and at least one suspected weight-related condition, and it’s the first new weight loss drug approved since 2014. But even that undersells how difficult it has been to find any treatment capable of helping people lose weight and keep it off.

Exercise is one of the best things you can do to have a long, healthy life, for instance, but it’s not a major driver of weight loss. Eating healthy is great, too, but even with sustained changes to your diet, it’s notoriously difficult to maintain long-term weight loss. And most medical treatments now marketed for weight loss only provide a modest boost, if any at all, while past treatments like Fen Phen and 2,4-Dinitrophenol (DNP) were pulled from the market for their dangerous, sometimes fatal side effects (DNP in particular could cause heat stroke by raising a person’s core body temperature too high). The most effective bariatric surgeries help people lose 20% to 30% of their original weight on average, but they are often an expensive and life-altering option that only a small percentage of those eligible for it actually take.

“[The results] were very impressive — it’s not something that any of the other drugs have gotten close to. So there’s really very strong reason to think about using this kind of drug as a primary form of weight loss,” Clifford Rosen, one of the editors at the New England Journal of Medicine who co-authored an editorial discussing Novo Nordisk’s research on semaglutide, told Gizmodo by phone.

Rosen, who is also director of clinical and translational research at the Maine Medical Centre Research Institute, added: “After the editorial came out, I got a note from one of my physician colleagues who said she lost like 16 kg with it, that it’s a miracle drug.”

On paper, Wegovy does seem to be the sort of miracle people worried about their weight dream about, particularly in the wake of scolding media coverage and research telling us that people have gained weight during the covid-19 pandemic. Even before the pandemic, it’s estimated that about 42% of American adults were obese from 2017 to 2018. In reality, though, it’s likely to be a more complicated bargain.

For one, there’s the problem of medical coverage. Traditionally, despite the possible health benefits, approved weight loss treatments are considered cosmetic, meaning that Wegovy wouldn’t be covered through basic insurance plans provided by employers or by the government via Medicare and Medicaid. And without coverage, Wegovy is expected to cost somewhere between $US1 ($1),000 ($1,361) and $US1 ($1),500 ($2,042) a month out of pocket, or somewhere around one-fifth of the median American’s household income annually.

On their website, Novo Nordisk is now offering potential patients coupons and other ways to save on out-of-pocket costs. It’s also reportedly doing a full court press in trying to convince private insurers and third party pharmacy benefit managers that Wegovy should be considered an essential treatment just like other medications taken for chronic conditions, including type 2 diabetes. But it’s not clear whether these efforts will bear fruit.

Of the several major insurers in the U.S. that Gizmodo reached out to regarding Wegovy, only Cigna responded. Soon after its approval, Cigna announced that its health services company Evernorth would include Wegovy for coverage in its specialty weight management program (the program is offered through Express Scripts, the pharmacy benefit manager that merged with Cigna in 2018). But it’s a plan that employers would have to agree to provide to employees and that employees would have to buy into first for them to gain access to Wegovy with a doctor’s prescription. Cigna’s own baseline coverage of Wegovy is up in the air.

“As with any newly approved medication, our independent Pharmaceuticals & Therapeutics committee will be reviewing Wegovy and making a coverage determination in the coming weeks,” Cigna said.

The situation looks even more dire for those on public plans. In the very statutes that established the Medicare Part D program in 2006, which provides coverage for prescription drugs, weight loss drugs are considered exempt from basic coverage. Individual Part D providers might still cover Wegovy, but only under enhanced plans, and state Medicaid plans are allowed to cover these drugs if they choose. But under the current law, a representative for Centres for Medicare & Medicaid Services told Gizmodo, basic Medicare plans will not cover weight loss drugs, Wegovy included.

Beyond the financial hurdles, there are the lingering long-term questions about semaglutide left unanswered.

Many common drugs we take, like antibiotics, are only taken for a brief time, until the relevant condition is cleared up. But it’s looking unlikely that semaglutide will be one of those, at least if you want the weight to stay gone. In another trial funded by Novo Nordisk, people who had taken the drug for about 20 weeks and then went off it were compared to those who had kept taking it for the next 48 weeks. While both groups remained at a lower BMI than before they started the trial, those off semaglutide regained more than half of the weight they lost on average, while maintainers continued to lose weight.

Sixty-eight weeks is a decent length for a clinical trial to run, but it still won’t represent the years, possibly decades of time that some users may take semaglutide. And though it was generally well tolerated in trials, with the most common side effects being the sort of temporary gastrointestinal symptoms described by Buckley and other users, there is at least a theoretical possibility of more serious or longer term risks. Acute pancreatitis, or an inflamed pancreas, has been rarely linked to GLP-1 use, which has raised concerns of a possible further risk of pancreatic cancer. And in trials with rats, GLP-1 drugs were found to raise the risk of a relatively rare form of thyroid cancer called medullary thyroid cancer.

There’s also precedent for this issue showing up with weight loss drugs. Just last year, the FDA successfully requested that Japanese pharmaceutical Eisai pull its appetite suppressant drug Belviq from the U.S., after postmarket safety data suggested that those on it were more likely to develop cancer.

There isn’t evidence that any such cancer risk exists with semaglutide specifically. But some researchers have noticed a possible connection between medullary thyroid cancer in people and different GLP-1 drugs. Other research, however, has so far found no connection between pancreatic cancer and GLP-1 use. All GLP-1 drugs on the market, including Wegovy, do warn people to be on the lookout for pancreatitis and warn doctors against prescribing them to people with a family history or genetic mutations linked to a higher risk of medullary thyroid cancer.

“These weight loss studies are powered for FDA approval based on short-term data. And if you really think about it, we haven’t had long-term drugs for weight loss. But now we’re talking five, 10 years for certain drugs. That’s a whole different ballgame. And yes, there may be some off-target effects,” Clifford Rosen said. At the same time, he added, the chances of finding something “startlingly off target” are probably very small, and he points out that some people with type 2 diabetes have been taking these drugs for years now, with no major issues reported.

It’s worth noting that other weight loss aids have carried a risk of abuse. These drugs have typically been stimulants, which can not only reduce appetite but also provide a sense of euphoria that can become addictive. But none of the experts I talked to believed that Wegovy would have a similar risk, at least in the same way that stimulants do. For one, it doesn’t seem to affect mood, and any person trying to take a much higher dose for would probably be dissuaded by the added probability of experiencing nausea and vomiting, Ryan said. She also felt that the possibility of people using it when not indicated, including people with disordered eating patterns like anorexia, was low for the time being, given its current prescription requirements.

“I am sure that people with anorexia might want to take Wegovy, as would people who want cosmetic weight loss but don’t meet BMI criteria, but it would be hard to get it, and no reputable physician would prescribe it,” she said. “In Brazil, the GLP-1 RAs are taken off label for cosmetic weight loss, but this has not occurred in the U.S. The price tag ($US1,300 ($1,770) per month) is a deterrent.”

No matter the drug, they all have their side effects and risks and have to be measured against the benefits they provide to see if they’re worthwhile for people to take. The FDA and many experts firmly believe that semaglutide meets that standard by treating obesity more effectively than any prescription drug that’s come along so far.

It’s a framing that presumes obesity and fatness are something to be repaired, though there’s disagreement on what that something is. The current medical consensus is that obesity is a chronic disease caused by a complex mix of not always controllable factors, including our environment and genetics — one that robs people of their good health and quality of life. Much of the general public, meanwhile, might agree that obesity is a serious health problem but still see it as an individual failing of lifestyle and willpower, despite the evidence that shows otherwise. Yet there are other people, including academic researchers and doctors, who are sceptical about both prevailing narratives. And to some of them, Wegovy isn’t a paradigm shift — it’s just more of the same propaganda they’ve seen their entire lives.

“It was immediate, these alarms in my head, because I was like, ‘There’s no such thing as a game-changer drug.’ In the past, with other medications that have been approved for weight loss, they have been extremely harmful, have had serious tolls on people taking them,“ Marquisele Mercedes, an activist in the fat acceptance movement, researcher, and doctoral student at Brown University’s School of Public Health, told Gizmodo by phone. “And pharmaceutical companies are notably shitty, so I was absolutely like, ‘There’s no way this is the whole story.’”

In late June, Mercedes wrote a detailed criticism of Wegovy’s approval and the praise surrounding it. Among other things, she noted that the trials used for approval were funded by Novo Nordisk and that many of the top researchers behind these studies or promoting the success of Wegovy had gotten research funding or outside payments from Novo Nordisk in the past. (Industry-funded research is an all-too-common practice, and these studies tend to provide rosier results than non-industry research.)

Mercedes also pointed out that the company once settled a lawsuit from the federal government and was forced to cough up $US60 ($82) million over its attempts to downplay the possible risks of medullary thyroid cancer from another of its antidiabetic GLP-1 drugs, Victoza, in its marketing to doctors. (At the same time, FDA had endorsed Victoza for its added benefits in reducing the risk of heart disease and stroke in type 2 diabetes patients.)

Aside from these arguments, the underlying premise of weight loss treatment that Mercedes and others in the fat acceptance and body positivity movements criticise — that it’s something that absolutely has to be treated — may be on shakier ground than most think.

“There’s this assumption that runs so deep — that if you’re fat, it’s going to be bad for your health, end of story. Like it’s not even questioned,” Harriet Brown, an author and journalist who has written about the science of weight loss, told Gizmodo. In the past, she’s argued that diets and other true-and-tired methods of weight loss are both ineffective and counterproductive to helping people stay healthy.

Plenty of people have lamented the use of BMI as a standard measure of health for many reasons. It’s well known, for instance, that two people with the same BMI can have very different types of bodies, depending on how tall they are and how much muscle and body fat they have. But more perplexing is that a higher BMI isn’t always neatly correlated to worse health. At least some studies have shown a so-called obesity paradox, where people who are overweight or mildly obese appear to live longer or have better health outcomes than people at “normal” BMI (people on either extremes of BMI tend to have the worst outcomes).

Some researchers have also argued that while people living with obesity do experience worse health in some ways, much of that harm can be attributed to the weight stigma and discrimination they face from others, including from their own doctors (weight stigma might even keep people from adopting healthy behaviours like exercise). Other studies have suggested that frequently losing weight, only to gain it back, can damage people permanently and could account for some of the health risk linked to obesity.

This debate over obesity and health remains contentious, and there’s a stronger link between obesity and certain health conditions, particularly type 2 diabetes, than there is for others (even so, most people with obesity do not develop diabetes). But it at least brings up the possibility that being overweight or obese in of itself isn’t the death sentence it’s commonly portrayed to be (some researchers have even called for BMI to be abandoned as a primary screening tool for health). And if that’s the case, then maybe Wegovy isn’t the answer to our prayers — not because it doesn’t work as intended, but because it’s trying to solve a perceived crisis of fatness that might not be dire as many think it is.

“My question would be: Does this drug — does it actually make people healthier? And I don’t think we have an answer to that.” Brown said.

Social movements related to fat activism have existed for decades, and as of late, seem to have only gotten more positive attention as concepts like body positivity have become mainstream (if not always productively). But that’s not to say there won’t be people eager for Wegovy. And for many of these potential users, Wegovy won’t just represent a sure-fire way to lose weight. Some obesity doctors and researchers argue that finally having an effective antiobesity drug on hand will help reduce weight stigma by making it clear that obesity isn’t a matter of willpower — it’s a metabolic condition that doctors now have a reliable way to manage.

Raychel Vasseur is one of the first customers of Calibrate, a company aiming to help people lose weight by pairing nutritional and lifestyle counseling with prescription medication, particularly GLP-1 drugs (Donna Ryan is one of Calibrate’s scientific advisors). According to Vasseur, she had been hesitant to take medication for weight loss. But after consulting with her Calibrate doctor, she felt it was the best thing to keep her metabolic problems and overall health under control. She said in an email that it has also helped reduce her cravings for often unhealthy foods, along with the fatigue she regularly experienced after eating them, writing, “I finally feel, for the first time in my life, that I don’t give food power anymore.”

In the months and years to come, Wegovy is likely to be only the first of many newfangled obesity treatments. Various pharmaceutical companies are running ongoing clinical trials of their own GLP-1 candidates, as well as drugs meant to mimic other gut hormones. This past May, Novo Nordisk released the preliminary results from a Phase I trial of semaglutide combined with the amylin analogue cagrilintide, which seemed to show an even greater weight loss effect than using semaglutide alone (albeit, with adverse events like nausea, vomiting, and indigestion being more frequently reported for the combination group).

Researchers like Donna Ryan are hopeful that future studies will not only demonstrate that GLP-1 drugs help people with obesity lose weight but also improve other markers of health. To that end, she’s one of many scientists behind the SELECT trial, which is measuring cardiovascular outcomes among overweight and obese people with a history of cardiovascular disease who take semaglutide or placebo.

“One of the barriers to obesity medicine is that we have not heretofore had evidence that weight loss improves hard outcomes (heart attack, stroke, death), only that it improves risk factors,” she said. “That is one thing that has contributed to the popular belief that weight is something that can be easily controlled and that obesity is really the patient’s fault.”

People who join Calibrate can enroll in a year-round program, which currently costs $US129 ($176) per month or $US1 ($1),550 ($2,110) per year. However, as part of this program, the company claims it will negotiate with private insurance companies to ensure drugs like Wegovy are covered, though those with high deductibles would still need to reach their out-of-pocket limit. According to Calibrate, it will refund customers if they’re unsatisfied with their insurance coverage.

And for those with Medicare who want Wegovy, that might be less of a problem in the future. This past March, Senators Kevin Cramer (R-ND), Tom Carper (D-DE), and Bill Cassidy (R-LA) reintroduced the Treat and Reduce Obesity Act, legislation that would remove the restriction of Medicare coverage for obesity treatments, including drugs like Wegovy. The bill is a rare example of bipartisanship these days, and it’s gotten backing from a long list of public health and obesity-related organisations. But it’s also gotten support from companies that would stand to benefit from the law, including Novo Nordisk, and two of the three co-sponsors have received significant campaign donations from the healthcare or insurance industry in recent years.

Wegovy may yet be the start of a new golden era for obesity research and treatment. And it may very well improve people’s health with little to no long-term complications, save for long-term weight reduction with continued use. But people like Mercedes and Brown fear what will come next if Wegovy does turn out to be every bit as popular and profitable as they expect it to be (even mediocre weight loss drugs like Novo Norodisk’s Saxenda have made around $US1 ($1) billion in annual sales recently).

Leaving aside any direct risks from the drug itself, Mercedes brings up the possibility of users going through cycles of losing and gaining weight if they try to stop taking it, or others feeling further stigmatised for not using Wegovy. She also takes umbrage with the idea that simply having more effective antiobesity drugs around will actually make life easier for fat people. She says that treating fatness as a disease, even for the sake of arguing that people’s obesity is not their fault, is still harmful.

“It doesn’t matter, because you’re still pathologising the condition,” Mercedes said, citing research suggesting that discrimination toward fat people, including from doctors, isn’t necessarily reduced when people believe that obesity is a disease. “So people are not going to experience less stigma just because there’s a medication that proves that their weight is not in their control.”

At the same time, Brown and Mercedes say they don’t begrudge anyone for wanting to take it.

“I totally understand why the idea of weight loss is appealing, and I would encourage anyone to do what it is they feel they want to do. But I would ask them to look at why they want to take this. Do you want to take this drug for the rest of your life, because you believe it will make you healthier? The jury’s out on that, I think,” Brown said. “But people will have other reasons in this fatphobic culture for wanting to live in a smaller body. And how can you not acknowledge that? I’ve been through that whole dieting cycle many times myself. But if health is really your concern, I would say that there are much more productive ways to go at thinking about that.”