JUANA SUMMERS, HOST:
Weight loss drugs like Wegovy and Zepbound are helping millions of Americans shed pounds, but these drugs affect the brain in ways that can cause nausea and other side effects. NPR's Jon Hamilton reports on researchers at the Society for Neuroscience meeting in San Diego who are trying to solve this problem.
JON HAMILTON, BYLINE: They're called GLP-1 drugs, and they mimic a hormone that reduces appetite and slows digestion. Warren Yacawych of the University of Michigan says, unfortunately, nearly half the people who take the drugs feel sick.
WARREN YACAWYCH: They lose weight, which is a positive thing, but they experience such severe nausea and vomiting that patients stop treatment.
HAMILTON: So Yacawych and his colleagues wanted to know if they could suppress appetite without making people queasy. He says they focused on two areas in the brain stem where GLP-1 drugs have a big effect.
YACAWYCH: The first is affectionately known as the brain stem's vomit center. It's naturally designed to detect any accidentally ingested toxin and coordinate the feeling of nausea and the vomit response.
HAMILTON: The second area monitors food intake and tells you when you're full. So the team altered mice in a way that allowed GLP-1 to reach the area involved in feeling full but not the vomit center. The mice didn't get sick, but Yacawych says they also didn't get thin - probably because certain cells in the vomit center are critical to weight loss.
YACAWYCH: And so it's very challenging, we think, right now to be able to separate these side effects, like nausea, from GLP-1's intended effects, like weight loss.
HAMILTON: One possible workaround came from researchers at the University of Washington. They gave obese rats a low dose of a GLP-1 drug along with the hormone oxytocin, which is itself an appetite suppressant. That allowed the rats to lose weight without feeling sick. Another side effect of GLP-1 drugs is a decrease in thirst. Derek Daniels of the University at Buffalo says this could be dangerous for people who are already losing lots of fluids from side effects like vomiting and diarrhea.
DEREK DANIELS: If you're in that state of dehydration and you're not feeling thirsty to replace those fluids, you can understand why that would be a problem.
HAMILTON: To understand how GLP-1 drugs affect thirst, Daniels and a team began studying rats, and they got lucky.
DANIELS: We had a happy accident in the lab, and the happy accident involved a rat called a Brattleboro rat.
HAMILTON: This animal is thirsty pretty much all the time, except when it gets a GLP-1 drug. This led the team to the brain area causing this change. Daniels says that discovery could be important in efforts to reduce side effects from GLP-1 drugs.
DANIELS: It now gives an opportunity to maybe design drugs that will target the good places and not the bad places. And I would think of a place that suppresses thirst as a bad place.
HAMILTON: Another team found that GLP-1 drugs are already targeting a place that plays a role in addiction as well as eating. It's a brain area involved in emotion and the reward system. Ali Guler of the University of Virginia says when GLP-1 is delivered to this brain area in mice, it doesn't affect their appetite for healthy foods.
ALI GULER: But if you do the same treatment and provide them with a rewarding food like a burger, the animals have actually a reduced intake of this food.
HAMILTON: It's the mouse equivalent of choosing a salad instead of dessert. And Guler says scientists should be able to develop versions of GLP-1 drugs that work the same way - by targeting the reward system while avoiding brain areas involved in appetite.
GULER: If we are able to do this, then we can use it for different types of treatments, such as substance use disorder like alcoholism or drug use.
HAMILTON: Doctors and researchers have already observed that people taking GLP-1 drugs for weight loss or diabetes tend to consume less alcohol.
Jon Hamilton, NPR News.
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