Researchers are investigating strategies to minimize nausea and other adverse effects associated with GLP-1 drugs like Wegovy and Zepbound. The focus is on targeting specific brain regions to maintain appetite suppression and address dehydration concerns.
Weight-loss drugs like Wegovy and Zepbound often cause nausea and other side effects . Brain scientists are looking for ways to solve this problem.Many people who take GLP-1 drugs like Wegovy and Zepbound for weight loss experience unpleasant side effects .
Brain scientists are trying to find ways to avoid those side effects.Warren Yacawych So at this year's Society for Neuroscience meeting in San Diego, Yacawych and other researchers held a session to describe their efforts to understand and solve the side-effect problem.Yacawych and his colleagues wanted to know if they could tweak these drugs to suppress appetite without making people queasy."The first is affectionately known as the brain stem's vomit center," Yacawych says."It's naturally designed to detect any accidentally ingested toxin and coordinate the feeling of nausea and the vomit response."The team found a way to direct GLP-1 to the area involved in feeling full, while keeping the drug out of the vomit center. When the researchers did this, the mice no longer felt sick. But they also didn't get thin — probably because there are specific cells in the vomit center that do not induce vomiting but are critical to weight loss. "So it's very challenging," Yacawych says,"to be able to separate these side effects, like nausea, from GLP-1's intended effects, like weight loss."of the University of Washington. They gave obese rats a low dose of a GLP-1 drug along with the hormoneAnother side effect of GLP-1 drugs is a decrease in thirst, which could be dangerous for people who are already losing lots of fluids from side effects like vomiting and diarrhea."If you're in that state of dehydration and you're not feeling thirsty to replace those fluids, that would be a problem," says To understand how GLP-1 drugs reduce thirst, Daniels and a team began studying the brains of rats. And they got lucky.Brattleboro rats are laboratory rodents with a genetic mutation that makes them thirsty nearly all the time. But the scientists discovered that these rats are also very sensitive to GLP-1 drugs, which drastically reduced their water consumption. The team studied the rats' brains to see where GLP-1 was influencing thirst. That led them to several areas of the brain that appear to affect thirst but not appetite.A team from the University of Virginia found that GLP-1 drugs are already targeting a brain area that plays a role in addiction as well as eating. It's a region involved in emotion and the reward system. When the researchers delivered GLP-1 to this brain area in mice, it reduced their desire for"rewarding food, like a burger," says But the animals continued to eat healthy, nonrewarding foods, he says — a bit like people choosing a salad bar over dessert. Identifying this brain area should help scientists find GLP-1 drugs that target the reward system while avoiding areas involved in appetite, Güler says. And that could lead to new treatments for alcoholism and other substance use disorders. The finding also could explain the observation that people who take GLP-1 agonists tend to reduce their consumption of alcohol.
Weight-Loss Drugs GLP-1 Drugs Side Effects Nausea Brain Research
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