More than 15 million adults in the U.S.—about 4.5% of the population—are using popular weight loss drugs like Ozempic and Wegovy.
While effective for many, these drugs can cause unpleasant side effects such as nausea, muscle loss, and even osteoporosis. They often require weekly injections and may stop working once treatment ends.
But now, researchers from Tufts University, led by Krishna Kumar, are working on a new, smarter drug with fewer downsides.
Their study, published in the Journal of the American Chemical Society, describes a compound that targets four different hormones related to appetite and metabolism, rather than just one, two, or three like current drugs. The idea is to improve weight loss while avoiding side effects that make current treatments hard to stick with.
Here’s how it works. After you eat, your body uses hormones as a fuel gauge to control hunger and blood sugar. One of these hormones is GLP-1. It helps regulate insulin and makes you feel full.
Drugs like Ozempic are based on GLP-1 and are now the top choice for managing diabetes. But GLP-1 can also cause strong nausea and must be injected weekly. About 40% of patients stop using it within a month because of this.
Another hormone, GIP, works like GLP-1 and also helps control appetite. To simplify treatment, scientists combined parts of both hormones into a single molecule, creating a “chimera.” The result is drugs like Mounjaro (tirzepatide), which appear to be more tolerable and cause fewer side effects.
Then there’s glucagon. Although it raises blood sugar, it also boosts energy use and suppresses appetite. Researchers found that by combining GLP-1, GIP, and glucagon in a single drug (like retatrutide), they could help people lose even more weight—up to 24%, which is close to the results of bariatric surgery.
Now, the Tufts team wants to go a step further. They introduced a fourth hormone: peptide YY (PYY). Released after meals, PYY also reduces appetite and slows digestion, but it works differently than the others. It might even help burn fat directly.
Because PYY is structurally different, combining it into a single drug was challenging. Instead of merging everything into one peptide, the researchers connected two peptides end-to-end, forming a new “tetra-functional” molecule.
This new design hopes to improve results across a wider group of patients, especially since people respond differently to hormone-based drugs. By targeting four hormone receptors at once, the new compound could lead to more consistent, long-lasting weight loss.
Another big problem with current drugs is that patients tend to regain weight once they stop taking them. This new compound may reduce that risk, especially if paired with healthy lifestyle changes. It might also help preserve muscle and bone, reducing some of the long-term risks seen with earlier treatments.
In the end, this new research from Tufts could bring us closer to achieving the weight loss power of bariatric surgery—without the need for surgery itself. That would be a huge step forward in treating obesity and the many diseases it can lead to.
If you care about obesity, please read studies about Scientists find new key cause of obesity and findings of Double whammy: diabetes drug also knocks out obesity.
For more about weight loss, please read studies about Scientists find secrets to long-term weight loss success and findings of Weight loss surgery linked to this mental disease.
The study is published in Journal of the American Chemical Society.
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