Opinion | GLP-1 Experimentation Is Everywhere, and Science Can’t Keep Up

In November 2017, on a bike ride to pick up her daughters from day care in Portland, Ore., Laurel Schmidt was hit by a car and tossed headfirst over her handlebars. She walked away with a bruised elbow and a headache that, over the next few days, became excruciating. She was in her mid-30s at the time. Her suffering didn’t meaningfully abate for nearly 10 years.

Ms. Schmidt was diagnosed with a traumatic brain injury and severe postconcussion syndrome with no cure. Frequently dizzy, with her vision impaired and her memory faltering, she felt as though she was living inside a snow globe, constantly “shaken up.”

She no longer trusted herself to cook, out of fear she’d forget to turn the stove off. She stopped driving after she noticed she couldn’t register traffic light changes quickly enough. Most days, she’d hide away in a dark room, seeing her children for only short periods of time.

That was until early 2025, when Ms. Schmidt discovered animal and cell research demonstrating that GLP-1s, the class of medicines that includes Ozempic and Wegovy, could potentially treat concussions. She tracked down several researchers involved in the studies, including the Indiana University chemist Richard DiMarchi. He suggested that she ask her doctor about trying a GLP-1 drug off-label, a common practice in which a medication is prescribed for a use that’s not yet formally approved.

Within days of starting on Zepbound last February, Ms. Schmidt felt her concussion symptoms finally begin to ease. A former endurance athlete and methodical tracker of all things, she used the Post-Concussion Symptom Scale to assess the severity of her condition. In the weeks following the crash, she scored over 100 out of a possible 132, indicating extreme impairment. When I talked to her last autumn, she had scored six.

On Thanksgiving she ran a Turkey Trot with her daughters — her first race since the accident. She described the turnaround to me as “miraculous.” Like so many people who are taking these drugs for intractable and varied symptoms, Ms. Schmidt had joined what we might call the great American GLP-1 experiment.

Technology moves fast, while science accumulates slowly. Humans have a history of rushing ahead with new technology, well before understanding how it affects us. (Just think of smartphones and ultraprocessed foods.) Still, GLP-1s may be a medical first: a blockbuster drug class, enthusiastically taken up by millions, not for one or a few uses but, it appears, a multitude.

They’re also the first blockbuster drugs to collide with our wellness-obsessed algorithmic age. People online tout microdosing GLP-1s for longevity; subreddits swap stories about using the medicines for menopause symptoms; fitness influencers promote unapproved formulations for bodybuilding.

So much of the experimentation with GLP-1s is happening outside of traditional research models, careful clinical trials and even the health system. Given the immense popularity of these drugs, regulators and the medical establishment need urgently to figure out how to best capture and keep pace with the experiment. Otherwise it risks spinning out of control.

In the last year, I’ve been talking to GLP-1 patients, as well as researchers and physicians, who are using or prescribing the drugs for an astounding range of diseases and conditions. Many report success: Debilitating long Covid symptoms dissolved. Decades of uncomfortable bouts of irritable bowel syndrome relieved. Patients said that the drugs loosened the grip of their addictions to drugs, cigarettes, alcohol and sex. Still others reported cognitive benefits like decreased anxiety and brain fog, and improved focus.

The tenor of these stories surprised me. Times Opinion asked the polling company Morning Consult to survey over 2,000 adults who have used GLP-1s. Before getting the results, I suspected that the reality of taking the drugs would be messier than the triumphalist headlines. The drugs can have unsavory side effects, most frequently nausea. Many people stop taking them because of those side effects and, perhaps even more so, cost and insurance barriers.

But the survey respondents were enthusiastic. Sixty-five percent of current or past GLP-1 users said they were “very interested” in continuing to take the drugs. More remarkably, 63 percent said that if their GLP-1 failed to help the condition it was initially prescribed to treat, they would either “definitely” or “probably” keep taking it for other benefits.

The poll results have limitations, as the answers are self-reported. But directionally, they suggested that people are finding relief where they hadn’t even been looking.

The more patients and physicians I’ve spoken to about this phenomenon, the clearer it has become: We are only at the beginning of the Ozempic era, but it is already shaping our culture and changing how disease is understood and treated. An estimated one in eight people in the United States alone have taken GLP-1s, placing the drugs among the most widely prescribed in the country right now. A significant number of those people are experimenting with off-label uses like Ms. Schmidt, or remaining on the drugs for unexpected benefits.

This experimentation is also driven by how the drugs seem to cut across the familiar borders of illness in ways that doctors haven’t seen before. “What we’ve come to realize,” said Dr. DiMarchi, who was a vice president at Eli Lilly and involved in GLP-1 research there, until he left the company in 2003, “is that many diseases may share the same root causes, even though we label them and treat them as distinct: This is an endocrine disease, this is a cardiovascular disease, this is a brain disease.”

This root-cause theory suggests that a wide range of conditions can be treatable with one drug class, sometimes through pathways in the brain and immune system. But, Dr. DiMarchi added, “What we know right now is small relative to what we don’t know.”

When GLP-1 medicines exploded onto the market for weight loss, experts offered a simple theory for how the drugs worked: They act as a souped-up version of a natural gut hormone, called GLP-1, which signals satiety. The idea was that the drugs mimic the body’s own hormonal signal, but more forcefully, making people feel fuller faster, eat less and ultimately lose weight. “And it’s just not true,” said Dr. Randy Seeley, a GLP-1 researcher and director of the University of Michigan’s Nutrition Obesity Research Center.

The GLP-1 hormone that our bodies produce — mostly in the gut and brain and, to a lesser extent, in the pancreas — “does almost nothing important physiologically,” said Dr. Daniel Drucker, a researcher based at Toronto’s Lunenfeld-Tanenbaum Research Institute, whose GLP-1 discoveries helped lay the foundation for today’s drugs. GLP-1 is among hundreds of chemical signals circulating in the body — part of the chorus that shapes our physiology and behavior, rather than a lead star.

What makes GLP-1 drugs so powerful is how the hormone behaves when given as medicine. GLP-1 receptors are found all over the body, and when people receive much higher, longer-lasting doses than humans produce naturally, a wide range of benefits surface.

In the case of obesity, the weight loss effects don’t come from the gut but originate in the brain. The brain has its own GLP-1 signaling system, which helps guide appetite in ways researchers are still just beginning to unravel. “The importance of native brain GLP-1 is still a bit of a mystery,” said Dr. Drucker, who, like Dr. Seeley, consults for GLP-1 drugmakers. Natural GLP-1 in the brain doesn’t seem to affect appetite much. When artificially raised, however, the brain’s GLP-1 system powerfully blunts the urge to eat.

Brain

Brain stem

Reward center

Hunger control

Stomach

Intestines

Pancreas

Fat cells

Scientists initially thought GLP-1s worked for weight loss by raising natural satiety signals in the gut.

But it turns out the weight loss effects may originate in the brain.

There are GLP-1 receptors throughout the brain. Important signals from the medicine get relayed through the brain stem and forwarded to deeper parts of the brain.

The brain stem also sends satiety signals out to the digestive system to promote fullness.

And it sends out messages to other parts of the body that further promote satiety and boost metabolism.

But GLP-1 receptors exist in many more organs, so there are probably even more mechanisms at play for weight loss that we have yet to discover.

Researchers discovered the weight loss effects of GLP-1s serendipitously. GLP-1 medicines were first approved for treating Type 2 diabetes, a disease where the body can’t properly use or doesn’t make enough insulin to control blood glucose levels, in 2005. As clinicians tried higher doses in clinical trials for diabetes, they began to notice patients spontaneously losing weight.

Unexpected benefits for kidney and liver disease turned up in the diabetes trials, too. The Food and Drug Administration requires drug companies to run studies investigating whether GLP-1s increase the risk of cardiovascular problems — a mandate for all diabetes drugs. These studies have shown a 20 percent reduction in heart attacks, strokes and death from cardiovascular problems. GLP-1s are now being prescribed for patients with conditions such as heart disease, sleep apnea and advanced fatty liver disease. Clinical trials are testing different uses of the medications for everything from treating arthritis to improving survival outcomes for cancer patients.

Part of this was predictable. Weight loss has long been known to enhance overall health and reduce the risk of everything from certain cancers to diabetes and cardiovascular problems. Since the drugs help people lose weight, it wasn’t surprising that they would deliver additional health gains.

“But what surprises everyone is how many benefits are weight independent,” said Dr. Seeley. In recent studies, the health gains for cardiovascular, liver and kidney disease, for example, happen regardless of whether patients lose weight.

Explaining why GLP-1 drugs improve health without weight loss defies simple narratives and confounds researchers. I’ve never come across another medical story where scientists repeatedly apologize for how bewildering their results appear to be. For each one of the effects they dig into, they come to different explanations for how the drugs help. In some cases, GLP-1s seem to target the organs involved in diseases directly, making them healthier. In other cases, the drugs help the body handle blood sugar and fat, making people “more metabolically flexible” and “biochemically more youthful,” said Dr. DiMarchi.

One of the most mysterious and fascinating ways they work is through reducing inflammation. Inflammation is part of the body’s natural response to injury and infection. It can signal healing, but it can also be present and harmful in the context of chronic disease. Dr. Drucker’s lab at the University of Toronto has pivoted from studying chronic diseases like diabetes and obesity to unraveling the immune system effects of GLP-1s. “We realized very quickly one underlying theme of all these was inflammation,” he said, of the diseases.

Before GLP-1s, medicines that targeted inflammation — like steroids — worked by shutting it down, suppressing the immune system and making patients more vulnerable to infections and cancer. The effects of GLP-1s appear to be more subtle. Researchers told me they believe the drugs “dampen” or “fine-tune” the immune response, without the “sledgehammer” effect of steroids. One called this a new frontier in medicine.

Dr. Drucker has found that the cells in the gut that produce GLP-1 seem to detect pathogens, releasing the hormone as part of the body’s response to injury or infection. The drugs may harness that effect. But even the anti-inflammatory narrative of how GLP-1 drugs work is complicated, depending on the type and location of inflammation involved. “We should not assume, as many do, that there is one simple way the drugs lower inflammation in all organs and conditions,” Dr. Drucker said.

In Ms. Schmidt’s case, Dr. DiMarchi suspects that the GLP-1 may have reduced damaging inflammation in her brain from her postconcussion syndrome, which played a role in her turnaround. “There’s incredible promise here,” said Dr. DiMarchi, who thinks there should be human trials testing GLP-1s for concussions. “But let’s not get ahead of ourselves.”

The momentum may be hard to rein in. Things are moving especially fast, and pill versions of GLP-1 drugs are now on the market. Patients, doctors and researchers are making observations about a range of new potential uses. Some of these benefits may eventually pan out in clinical trials, but others won’t.

There already have been notable disappointments, and even claims that the drugs caused serious side effects. There are numerous lawsuits from people toward companies blaming their GLP-1s for health complications like serious stomach problems, and alleging that they weren’t properly warned of potential risks.

In November 2025, the drugmaker Novo Nordisk announced that two large and much anticipated studies failed to find any benefit for its GLP-1 medicine in patients with early stage Alzheimer’s disease. Studies of Parkinson’s disease and cognitive impairment in major depression have also fallen short. It could be that researchers just haven’t figured out the right doses, protocols or combinations of GLP-1-based molecules. Or it could be that the drugs won’t work well enough for these conditions.

Even the most riveting stories people have shared of their experiences suggesting that GLP-1s can curb addiction gave many of the researchers I interviewed pause. The trials to date have been mixed, and some experts wondered if the effects people initially reported will persist.

Dr. Drucker said he gets emails almost every day from patients about how GLP-1s treated their addictions or caused miraculous turnarounds like Ms. Schmidt’s. He doesn’t doubt that the cases are real. They’ve even spurred new research directions in his lab, such as studies focused on arthritis. “The question I always have is if I treated 100 people with concussion or 100 people with long Covid, would the response rate be 35 to 40 percent, in which case, wow, this is really useful as a medicine, or 3 percent?”

Health institutions must figure out how to harness the data the great GLP-1 experiment is yielding. Publicly funded research agencies like the National Institutes of Health could play an important role by rapidly investigating the most promising uses of GLP-1 drugs, particularly in areas where pharmaceutical companies may be reluctant to invest, such as traumatic brain injury, for which trials are difficult to run. If done well, more people might find life-altering relief and others could be spared harm.

Right now, the potential for injury and misuse is high. Many people report getting GLP-1s through online telemedicine companies, where a doctor is required to evaluate and prescribe the drug, but barriers to entry can be too low. The telehealth company Hims, which has sold branded and compounded GLP-1s, recently announced plans to offer a cheaper pill form of the GLP-1. The company quickly had to backpedal amid legal action from Novo Nordisk.

“There’s just so much medicine happening outside of the actual medical system,” said Dr. Beverly Tchang, an assistant professor of clinical medicine at Weill Cornell, who works as an adviser for the telehealth company Ro. “It’s happening within these telehealth companies, within the internet, over the gray market, and no one has any insight into it.”

Meanwhile, insurance barriers have helped fuel markets for unregulated GLP-1s, including for cheaper compounded versions of the drugs (medications that are custom mixed to mimic brand-name drugs). The patients who could most benefit from GLP-1s for obesity and diabetes — low-income, structurally disadvantaged groups in whom diet-related diseases are concentrated — often can’t get access to them. The medication is largely not covered by insurance for anything but approved uses. And even among the insured, gaining coverage for weight loss remains challenging. One patient I spoke to had been using compounded GLP-1s to manage her lupus symptoms because of cost issues, and was increasing her dose without consulting her a doctor whenever she felt its effects plateau.

The case for cost savings to the public purse is also murky. For diabetes and obesity, the benefits of GLP-1s depend on long-term use. When people stop taking the medication, their weight — and health risks — oftentimes rebound. Given the scale of current spending on these drugs, that relapse can feel like money thrown away.

While we await better data and guardrails, there will be more GLP-1 mass improvisation. The Trump administration has worked with drug companies to lower the cost of GLP-1 medicines. The patent for semaglutide, a type of GLP-1 drug, is expiring in several countries, including Canada. As more GLP-1s are offered in oral form and generic competition production ramps up, global use of the drugs is expected to surge.

I asked Drs. Seeley and Drucker if, given the drugs’ anti-inflammatory effects and range of positive research outcomes, we should all be on GLP-1s. The answer was an unambiguous no. “I’m not a GLP-1 in the drinking water kind of guy,” Dr. Drucker said.

A lot of what we know about the drugs so far comes from data in people with diabetes and obesity, Dr. Seeley pointed out, not healthy people trying to do things like manage menopause symptoms or microdose to extend their life spans. Much of the long-term safety data also comes from early versions of the drugs. Newer formulations that target multiple GLP-1 receptors are gaining widespread fervor online and may be even more effective for issues like weight loss, but we have limited data on their long-term risks and benefits. Even when patients consult their doctors, as Ms. Schmidt did, clinicians may struggle to navigate risks for novel uses amid so many unknowns.

Dr. Seeley imagined a hypothetical patient with obesity who is diagnosed with breast cancer. Obesity increases the risk of cancer recurrence, so GLP-1s could lower her risk. But if the drug is anti-inflammatory and she’s on a cancer medication that targets her immune system, he wondered, “is that going to interfere with her therapy?” No one knows.

But the fact that so many people are already on GLP-1s for such a broad variety of reasons, with potentially millions more rapidly joining the fold, suggests that “we cannot clinical trial our way out,” Dr. Seeley said, referring to carefully testing every potential indication before it is enthusiastically taken up.

Social media is already buzzing with people sharing their successes on retatrutide, the weight loss drug still under study that targets GLP-1 and two other hormone receptors. Reta, as it’s known on the internet, appears to produce even greater weight loss than the already F.D.A.-approved GLP-1s. Health optimizers are buying up unregulated versions of it online.

These “leanmaxxing” or bodybuilding TikTokers and Redditors post dramatic before-and-after photos and videos about how to dose and administer injections or supplement retatrutide with other compounds. Some urge their followers to send them private messages for links to their legally questionable sources. The podcaster Andrew Huberman has called retatrutide the “trillion-dollar drug” that’s going to “change everything.”

So much has changed already. Basic science and careful clinical trials gave us what appears to be, for many, a wonder drug. Yet we don’t have the systems and structures in place to understand how it’s really being used, and who could most benefit while protecting others from risk. Our traditional regulatory and health systems weren’t built for this kind of experimentation outside the medical system.

Finding ways to better study GLP-1 users going it alone is a place to start. Many of the patients I spoke to were eager to understand their own results, including Ms. Schmidt. Traumatic brain injuries can shorten life spans, she told me, and increase the risk of dementia. When she started documenting her symptoms, she said it was “in the hopes that someone someday would study this more.” For now, she isn’t sure why the medication worked for her or how long she would take it. She just hoped for a long and healthy life. “What does the future look like? I don’t know.”