The one, big unanswered question about Ozempic

Vox

28-07-2025

covers health for Vox, guiding readers through the emerging opportunities and challenges in improving our health. He has reported on health policy for more than 10 years, writing for Governing magazine, Talking Points Memo, and STAT before joining Vox in 2017.
We are nearing a point of no return for GLP-1 drugs.
More than one in 10 Americans have already taken a GLP-1 agonist, be it Ozempic, Wegovy or Mounjaro. The medications, originally developed for diabetes treatment, have proven to be remarkably effective in helping people lose weight — and America is in the throes of an obesity crisis. They have shown promise in treating cardiovascular diseases, the country's leading killer and a direct consequence of the obesity epidemic.
With each additional study finding yet another application for these drugs, you might find yourself asking: Should I be taking Ozempic? Should everybody take it? Is there anything these drugs can't do?
And indeed, right now it can seem like everyone will be taking GLP-1, sooner or later. These drugs currently require regular injections and can cost more than $1,000 out of pocket, but cheaper and more easily used versions are coming.
Eli Lilly will soon bring a pill version to the market, with a version expected to debut at a lower price than injectable Ozempic or Wegovy did.
A generic GLP-1 agonist is on track to arrive at Canadian pharmacies in 2026 and a US version will likely follow within the next decade. Some of the newer versions in development may prove to be even more effective than the first generation, which will only create more demand among doctors and patients.
Put it all together, and we can expect many, many more people taking them. GLP-1 drug prescriptions for adults with commercial insurance increased by a staggering 364 percent from 2019 to 2024, but they were still only prescribed to 4 percent of insured US adults; more than 100 million US adults — 40 percent of the population — are obese, the Wall Street Journal reported earlier this year, and as more insurers cover these drugs for weight loss, more patients will be able to access them.
These drugs' power comes from their mysterious ability to control people's compulsions. Patients who take an GLP-1 agonist say that the fatty ultraprocessed foods they used to find irresistible are no longer so tempting, though sometimes those old cravings for unhealthy junk come rushing back after taking the drugs for a while. Substances as habit-forming as coffee no longer hold the same sway. Others notice decreased desires that have nothing to do with their diet — to bite their nails, for example.
We are entering the Ozempic era, and even as excitement grows about the possibilities for these medications, now is the time to take seriously the possible risks from this new class of drugs.
A lot of people experience brand-new cravings, sometimes for healthier foods. 'Beans — I get cravings for beans. I never really ate them before, now I crave homemade baked beans in a tomato sauce,' Sarah, a charity development worker from Scotland who has been taking a GLP-1 compound for a few months, told me by email. 'It used to bother me if a cafe served beans on a cooked breakfast; now beans is the main part of my breakfast.'
Swapping salad greens for carbs sound like a clear win — in fact, it sounds almost too good to be true. In the long term, what does it mean to modulate our desire? Are we sure we can suppress the harmful compulsion to eat too much without compromising the productive ones — such as the desire to succeed or the pleasure we find in personal relationships? How might these drugs impact our experience of joy and pain? What might that do to impact the messy human experience of…simply living?
'What are the very long-term effects of these drugs? The literature will say, 'Well, there isn't really bad long-term effects because some people have been taking it for diabetes for 10 years, and they don't have bad effects,'' Kent Berridge, a professor of psychology and neuroscience at the University of Michigan, told me. 'And I think that's a fair argument. But then 10 years is not 20 years or 30 years.'
We are entering the Ozempic era, and even as excitement grows about the possibilities for these medications, now is the time to take seriously the possible risks from this new class of drugs. In my conversations with some of the top experts on the science of cravings, they offered a cautious outlook in regard to messing with our brain's desire pathways. But they were also optimistic that these drugs could deliver benefits to many Americans without turning us into emotionless robots.
Why GLP-1s work for so many different medical conditions
In the 1980s, scientists had identified the naturally occurring hormone GLP-1 and its importance in regulating people's digestion. By the end of the decade, investigators had confirmed that the hormone encouraged insulin production — offering the potential to treat people with diabetes, who struggle to produce insulin that regulates their blood sugar. Then just a few years later, a scientist identified a peptide from the Gila monster that was similar to the human hormone GLP-1 but came in a more stable form, offering therapeutic potential.
By the mid-2000s, the first GLP-1 agonist drugs were approved for diabetes, but the daily injections required and the narrow focus kept the market small. In 2017, the Food and Drug Administration approved Ozempic — a weekly injection, rather than a daily shot. By that point, doctors had already begun to notice that some patients who took the GLP-1 agonists experienced a reduced appetite with resulting weight loss. Researchers began to study the weight-loss effects and they were stunned: One of the first studies found users lost 15 percent of their body weight, on average, in little more than a year, a wildly larger percentage than from any other weight loss drug or tool.
The Ozempic fervor had begun. Specialty pharmacies started to sell off-brand compounded versions of the drugs. The FDA then approved Wegovy, an Ozempic successor, for weight loss in 2021, and in 2023, Zepbound got the green light for weight-loss prescriptions.
As their astonishing weight-loss effects became clear, research into GLP-1 agonists and their health benefits exploded. Today, the list of possible benefits is genuinely astounding.
But how, exactly, do they work?
First, a drug like Ozempic mimics the natural GLP-1 hormone in your gut, which slows down digestion in the stomach and gastrointestinal tract. Those who take it feel fuller earlier and longer, and it's easier for them to eat less. The better regulation of blood sugar also prevents massive swings in glucose, which can induce hunger.
As a result of its effect on digestion, the most common clinical side effects reported with Ozempic and its peers are nausea, vomiting, diarrhea and constipation. In clinical trials for GLP-1 treatment for diabetes or obesity, between 4 and 12 percent of patients experienced constipation; a similar share of patients endured vomiting and diarrhea. There have been reports of other rare but serious physical side effects: The drugs have been linked to an elevated risk of eye disease among older patients, for example. Some people who lose weight quickly experience temporary hair loss, a symptom that a small number of patients on GLP-1 medications have anecdotally reported.
But scientists have also discovered these drugs can affect your brain directly, with sometimes surprising and unpredictable effects on people's cravings — for food and for other things.
Naturally occurring GLP-1 secretes from in a person's intestines into their blood and it disappears within a matter of minutes, destroyed by enzymes in the blood, Berridge said. As a result, it does not cross into people's brains very easily. The drug form, GLP-1 agonists, on the other hand, can cross this barrier.
When a person takes Ozempic or Wegovey or whichever GLP-1 they've been prescribed, the semaglutide endures for a long time, giving it more time to cross into the brain. Once the chemical is in that person's brain, it can turbocharge neurons in your brainstem that naturally produce some very small amounts of GLP-1. Those neurons then release the hormone into many other parts of the brain and disrupt the release of dopamine, which produces that little surge of pleasure that makes eating a sweet sugary piece of cake so damn good or finishing a half marathon after months of training so satisfying.
'The drugs are getting into these structures and it turns out that they suppress cravings in all of these places, including the reward-system ones,' Berridge said.
Scientists began to make this connection when observational studies reported that people who took a GLP-1 agonist for its diabetes or weight-loss effects also reported consuming less alcohol or fewer illicit drugs than they did before. Researchers started to probe further, experimenting with injecting microdoses of a semaglutide directly into the brains of animals in lab studies, and they have found a decrease in all kinds of cravings, including powerful compulsions for cocaine and heroin.
These findings have introduced the startling possibility that, beyond food, we could control some of the most uncontrollable urges that people struggle with, often to the detriment of their health.
But they also bring us to the big question: If we can turn down the volume of our desire, how might that change the very emotions that make us human, the experience of our deepest joys and pleasures?
What the science on desire can tell us about GLP-1s
I've started to think of the dilemma these drugs present this way: Can I cut off the part of my brain that compels me to reach for a bag of potato chips at night, without compromising the desire to sit down and read books with my children?
Unfortunately, we simply don't know yet. Scientists aren't exactly sure how these complex human desires interact. The desire to eat, for example, is one of our oldest evolutionary impulses, Berridge, the Michigan neuroscientist, told me. Can we really mess with that ancient part of our brain without unintended consequences?
There are at least two ways of thinking about what the answer might be.
First, the (maybe) good news: Berridge's research has focused on the distinction between wanting something and liking it. He told me if Ozempic can eliminate our unchecked wanting of something that's bad for us — such as fatty, processed foods or alcohol, for example — but still maintain our enjoyment of it, that would suggest people who take it are not suddenly at risk of losing all of the pleasure in their lives, including other things that also cause a surge of dopamine in our brains, like finishing a creative writing project after months of work or cherishing conversations with your friends.
This is a concept that my former colleague Brian Resnick explored last year: GLP-1s have the ability to manipulate a figurative 'dial of desire' in our brains, which could be leveraged for good.
In the 1980s, Berridge worked on a series of experiments with a colleague, Terry Robinson, in which they eliminated dopamine in rats. What they observed was the rats stopped voluntarily eating, drinking, and seeking other rewards set up by the investigators. However, when they were given something sweet to eat, their faces would react positively to the taste, just as they normally would. That reactivity, the researchers postured, was a proxy for their joy. The rats could also still become averse to new sensations, which again affirmed a capacity for strong emotions, even if their compulsiveness had been removed.
Berridge told me he actually doubted their findings at first — how could you like something but not want it? — but it continued to be replicated in experiments by other investigators over the years. In one particularly revealing experiment from 2005, participants were given cocaine and a dopamine-blocking drug. They still liked the cocaine when they were given it, but their desire for additional cocaine was dampened when the dopamine was blocked. The study was small, but it affirmed Berridge and Robinson's initial insight: Dopamine appears to influence the wanting of things, rather than the liking of them.
Early studies of Ozempic patients indicate most participants still enjoy their food despite their compulsion to eat being reduced. Some of them, including some of the patients I spoke with, also found themselves desiring healthier foods. 'That's encouraging,' Berridge told me. 'I would say that's a good thing.'
However, another way of understanding desire would raise more cause for concern. Jackie Andrade, a psychology professor at the University of Plymouth, has worked with colleagues on the Elaborated Intrusion Theory, which proposes that all our cravings are not unique brain processes but part of our general motivation. According to this theory, when we encounter certain 'triggers' — such as a physical sensation or some environmental cue — the trigger leads to a burst of spontaneous thoughts about an object of our desires. And when we begin mentally picturing our desire, our craving for it only increases.
Here is the key finding, Andrade told me: The object of desire — whether it be alcohol, chocolate, or cigarettes — is less important than the underlying mental processes involved in craving. The brain mechanisms are the same regardless of the craving, based on their observations of people's brain patterns when being presented with different triggers. We crave something because the image of it in our minds is briefly pleasurable and thinking about whatever it is boosts our mood, which in turn strengthens the craving and our awareness that we don't have it.
This explains one of the conundrums about desire: Our desires are thoughts and thoughts require mental effort. So why aren't they easier to shake? This cycle of environmental triggers — seeing a billboard advertising fast food or attending a cookout with chips and dip on display — leads to our imagining the craving, which leads to both pleasure if we satisfy it and frustration if we don't, which is why we feel such strong impulses to resolve the cravings. But, at least according to the Plymouth researchers' work, there is not a clear distinction between a craving for a piece of pizza and a craving for something more productive.
'From our research, the cognitive processes are the same for both,' Andrade said. 'Could we have less driven entrepreneurs or marathon runners because they're on these drugs and they're too chilled out to want to do anything? Right now, we don't know.'
What we still need to figure out about these drugs
Even as their usage explodes, the reality behind these drugs and how they affect our desires is still a mystery. Pills are likely to have the same effect as injections on cravings, Berridge told me, so long as the GLP-1 agonist is still crossing into people's brains.
'In what sense is it reducing wanting? Because there's a couple of possible ways. One way would be to subtract a degree of intensity from every want,' Berridge said. 'So addictive wants go down, but then so do the everyday desires in life and even eagerness to go out into the world and face it and do things. That would be bad if it was a general subtraction in intensity of wanting.'
'On the other hand, it is possible that that's not what it's doing, but rather it's lowering the ceiling,' he continued. 'So really intense peaks of wanting can't go so high, but things below that ceiling can still remain normal.'
In other words, GLP-1 agonists can only decrease the intense peaks of our cravings, which could allow us to, for example, not binge-eat or overdrink — without eliminating a more normal intensity of wanting for other things.
The problem is, Berridge said: 'I don't know of any actual studies that have asked this question.' He said he would like to see a study that measures people's motivation to pursue a wide range of incentives, both mild and intense ones, when on and off one of these drugs. Researchers at the University of Plymouth are setting up studies that would evaluate behavioral changes in people who take the GLP-1 medications.
We need more evidence, because what we have right now is circumstantial and inconclusive anecdotes. Peruse the many Reddit communities devoted to these weight-loss drugs and you'll see the subject of cravings come up a lot. Some people describe food cravings that come back after a few months of taking Ozempic or Wegovy. Others report strange new cravings they never experienced before, such as a sudden taste for milk. Some of the changes are expected — decreased desire for nicotine or alcohol — but some are puzzling: One user, a true crime aficionado, described a reduced desire to look at dark or gory materials online after being on a GLP-1 agonist. Others responded by sharing that they were less compelled to shop online or stopped biting their nails.
Sarah, the charity development worker from Scotland, told me she started taking a GLP-1 drug three months ago after she gained weight during perimenopause and was struggling to lose it. She's since lost 18 pounds. There have been some physical side effects — fatigue and acid reflux — and she's noticed a significant shift in her cravings. Whereas she used to mix salads with pasta, she finds she no longer craves the carbs. Mashed potatoes used to be one of her favorite foods, but she hasn't eaten that once since going on the medication. At the same time, she has new hankerings for beans and green apples — which she told me she found puzzling because she says she used to hate the sound of teeth crunching into an apple.
'I don't get the same emotions from food,' she told me over email. 'It's nice, I enjoy it, but I don't feel food in the same way.'
She, like many other patients, also says she no longer experiences the same desire to drink alcohol. She told me she drinks at most one night on the weekend and no longer attends happy hours with her colleagues like she used to, when she would have a few drinks midweek. 'I don't go and not drink, I just don't go,' she told me. 'Drunk people are tedious when you're sober!'
GLP-1s are genuinely promising, but they also reveal our insatiable desire to find a wonder drug that takes care of all of our problems in one pill. Andrade said we should resist that temptation, even if Ozempic and its peers could play a role in helping to address important health crises.
Research has consistently found that weight loss tends to be more sustainable when it includes behavioral changes in addition to pharmaceutical interventions. Ideally, you would do both: work on modifying your behavior, while medication assists. Losing weight isn't just about eating less, but eating healthier and exercising more in order to enjoy the health benefits that those positive activities produce. If Ozempic affects all kinds of motivation, patients may not be as driven to adopt those other desirable behaviors.
'If people are taking these drugs, are they more motivated to, say, become more physically active or to eat more healthily? Or are they less motivated because the drugs are doing it for them?' Andrade said. 'There's the risk that people might not want to make changes. If you've still got a bad diet and a sedentary lifestyle, you're building up other problems that are maybe a little bit more hidden because the obesity is not there.'
This is already an ongoing subject of concern: Some studies have suggested that people who stop taking Ozempic gain back much of the weight they lost; that may be because they are not adopting desirable new behaviors — better eating, more activity — alongside their taking the drug. On the flip side, some doctors say they also worry about people who take the drugs for reasons other than weight loss but end up undereating and increasing the related health risks of undernourishment.
Are these findings a canary in the coal mine for other unexpected and undesirable side effects related to the drug's effects on cravings?
It's a genuinely vexing question. After all, many people take these drugs because they do have a problematic compulsive behavior — they eat too much. Getting those cravings under control is the point of getting a prescription. But are people also losing other less obvious desires? Are they losing, in a sense, a part of themselves?
The evidence for now is mixed. One Reddit user joked they felt like they were getting mental health care they didn't know they needed. Two Reddit users shared that they had cut down from multiple cups of coffee in the morning to one (or less). 'I'm kind of bummed about it,' one said. 'I love my coffee.'
'Same. I love coffee,' the other poster replied.