In the beginning, weight loss was just a side effect. GLP-1 RAs were first developed to treat type 2 diabetes; their hormone-mimicking action provokes insulin production. In 2005, the US Food and Drug Administration approved the first drug of this kind, Exenatide, for diabetics. Throughout the 2000s, more and more GLP-1 RAs came onto the market. Right away, patients noticed that these drugs didn’t just treat their diabetes—they also helped them lose weight.
Ozempic and Wegovy, the brand names of a GLP-1 RA known as semaglutide, are both made by Novo Nordisk, a Danish pharmaceutical company. Though they both contain the same active ingredient, the drugs have different indications, dosages, prescribing information, titration schedules, and delivery devices. In 2017, Ozempic was first approved as a diabetes treatment, and doctors soon began to prescribe it off-label to overweight patients. Subsequently, Novo Nordisk developed Wegovy specifically for weight loss. In June 2021, it became the first new treatment for chronic obesity approved by the FDA since 2014.
Then, in May 2022, the FDA approved Mounjaro as a diabetes treatment; now the agency is officially “fast-tracking” the investigation of its active ingredient, tirzepatide, for obesity. A spokesperson for the drug’s manufacturer, Eli Lilly, said it is presently only approved for glycemic control in adults with type 2 diabetes and the company “does not promote or encourage use of Mounjaro outside of its FDA-approved indication.” Nonetheless, since the drug came to market, doctors have been prescribing it off-label for weight loss—there are almost 100,000 members in a Facebook group called “Mounjaro Weight Loss Success.”
Clinical trials have shown that tirzepatide patients lose at least 20% of their weight in 72 weeks, while overweight adults on Wegovy lose an average of 15% of their body weight in 68 weeks.
Edenfield is one such success story. Unable to work at the height of the pandemic, he had stayed at home “eating a lot and eating very unhealthy.” He compares his diet to a teenager’s: regular consumption of fast food sandwiches, cheese steaks, and burgers accompanied a “crippling addiction” to Coca-Cola. When his weight crept up to 357 pounds (he is 6 feet 3 inches tall), he sought gastric sleeve surgery because his employer would cover the cost. Yet the doctor he met with suggested Ozempic instead. He lost 15 pounds in his first month on the drug and switched to Wegovy in February 2022. He now weighs 228.
COURTESY OF MICHAEL EDENFIELD
“It’s changed every aspect of my life,” Edenfield says—he no longer feels “hijacked” by hunger and doesn’t get out of breath walking to work. “I feel like I’m in my 20s again,” he says.
The results may be enviable, but the day-to-day reality of weight-loss injections is not always pleasant. The most common side effects are gastrointestinal, including nausea, diarrhea, and constipation. Edenfield consulted Reddit for tips on alleviating “brutal” nausea. A number of subreddits dedicated to semaglutide have sprung up or grown in popularity over the last year—the one Edenfield posted on was created in 2021 and has almost 22,000 members today. Meanwhile, countless Facebook groups have also been created during the weight-loss injection boom. Here, people report experiencing vomiting, headaches, fatigue, “sulfur burps,” and hair loss—though the vast majority seem to feel it’s a small price to pay for losing weight.
During the 68-week Wegovy trial, 4.5% of participants discontinued treatment because of gastrointestinal events. Peter Kurtzhals, Novo Nordisk’s chief scientific advisor, says that such side effects normally decline gradually as patients build up a tolerance to the drug. A company spokesperson adds that patients experiencing nausea on Wegovy “should contact their health-care provider, who can offer guidance on ways to manage it.”
Leggett told researchers that she “became one” with her device. It helped her to control the unpredictable, violent seizures she routinely experienced, and allowed her to take charge of her own life. So she was devastated when, two years later, she was told she had to remove the implant because the company that made it had gone bust.
The removal of this implant, and others like it, might represent a breach of human rights, ethicists say in a paper published earlier this month. And the issue will only become more pressing as the brain implant market grows in the coming years and more people receive devices like Leggett’s. Read the full story.
—Jessica Hamzelou
You can read more about what happens to patients when their life-changing brain implants are removed against their wishes in the latest issue of The Checkup, Jessica’s weekly newsletter giving you the inside track on all things biotech. Sign up to receive it in your inbox every Thursday.
If you’d like to read more about brain implants, why not check out:
+ Brain waves can tell us how much pain someone is in. The research could open doors for personalized brain therapies to target and treat the worst kinds of chronic pain. Read the full story.
+ An ALS patient set a record for communicating via a brain implant. Brain interfaces could let paralyzed people speak at almost normal speeds. Read the full story.
+ Here’s how personalized brain stimulation could treat depression. Implants that track and optimize our brain activity are on the way. Read the full story.
Burkhart’s device was implanted in his brain around nine years ago, a few years after he was left unable to move his limbs following a diving accident. He volunteered to trial the device, which enabled him to move his hand and fingers. But it had to be removed seven and a half years later.
His particular implant was a small set of 100 electrodes, carefully inserted into a part of the brain that helps control movement. It worked by recording brain activity and sending these recordings to a computer, where they were processed using an algorithm. This was connected to a sleeve of electrodes worn on the arm. The idea was to translate thoughts of movement into electrical signals that would trigger movement.
Burkhart was the first to receive the implant, in 2014; he was 24 years old. Once he had recovered from the surgery, he began a training program to learn how to use it. Three times a week for around a year and a half, he visited a lab where the implant could be connected to a computer via a cable leading out of his head.
“It worked really well,” says Burkhart. “We started off just being able to open and close my hand, but after some time we were able to do individual finger movements.” He was eventually able to combine movements and control his grip strength. He was even able to play Guitar Hero.
“There was a lot that I was able to do, which was exciting,” he says. “But it was also still limited.” Not only was he only able to use the device in the lab, but he could only perform lab-based tasks. “Any of the activities we would do would be simplified,” he says.
For example, he could pour a bottle out, but it was only a bottle of beads, because the researchers didn’t want liquids around the electrical equipment. “It was kind of a bummer it wasn’t changing everything in my life, because I had seen how beneficial it could be,” he says.
At any rate, the device worked so well that the team extended the trial. Burkhart was initially meant to have the implant in place for 12 to 18 months, he says. “But everything was really successful … so we were able to continue on for quite a while after that.” The trial was extended on an annual basis, and Burkhart continued to visit the lab twice a week.
“A patient should not have to undergo forcible explantation of a device,” says Nita Farahany, a legal scholar and ethicist at Duke University in North Carolina, who has written a book about neuro rights.
“If there is evidence that a brain-computer interface could become part of the self of the human being, then it seems that under no condition besides medical necessity should it be allowed for that BCI to be explanted without the consent of the human user,” says Ienca. “If that is constitutive of the person, then you’re basically removing something constitutive of the person against their will.” Ienca likens it to the forced removal of organs, which is forbidden in international law.
Mark Cook, a neurologist who worked on the trial Leggett volunteered for, has sympathy with the company, which he says was “ahead of its time.” “I get a lot of correspondence about this; a lot of people inquiring about how wicked it was,” he says. But Cook feels that outcomes like this are always a possibility in medical trials of drugs and devices. He stresses that it’s important for participants to be fully aware of these possibilities before they take part in such trials.
Ienca and Gilbert, however, think something needs to change. Companies should have insurance that covers the maintenance of devices should volunteers need to keep them beyond the end of a clinical trial, for example. Or perhaps states could intervene and provide the necessary funding.
Burkhart has his own suggestions. “These companies need to have the responsibility of supporting these devices in one way or another,” he says. At minimum, companies should set aside funds that cover ongoing maintenance of the devices and their removal only when the user is ready, he says.
Burkhart also thinks the industry could do with a set of standards that allow components to be used in multiple devices. Take batteries, for example. It would be easier to replace a battery in one device if the same batteries were used by every company in the field, he points out. Farahany agrees. “A potential solution … is making devices interoperable so that it can be serviced by others over time,” she says.
“These kinds of challenges that we’re now observing for the first time will become more and more common in future,” says Ienca. Several big companies, including Blackrock Neurotech and Precision Neuroscience, are making significant investments in brain implant technologies. And a search for “brain-computer interface” on an online clinical trials registry gives more than 150 results. Burkhart believes around 30 to 35 people have received brain-computer interfaces similar to his.
Leggett has expressed an interest in future trials of brain implants, but her recent stroke will probably render her ineligible for other studies, says Gilbert. Since the trial ended, she has been trying various combinations of medicines to help manage her seizures. She still misses her implant.
“To finally switch off my device was the beginning of a mourning period for me,” she told Gilbert. “A loss—a feeling like I’d lost something precious and dear to me that could never be replaced. It was a part of me.”
