Weight loss drugs like Ozempic and Wegovy have become popular in the U.S., with over 15 million adults using them. These medications help control blood sugar and appetite and are effective in promoting weight loss.
However, they come with challenges, such as side effects like nausea, muscle loss, and the risk of regaining weight after stopping treatment.
Now, researchers at Tufts University, led by Professor Krishna Kumar, have designed a new next-generation drug that could work better and cause fewer side effects. Their study was recently published in the Journal of the American Chemical Society.
Current weight loss drugs work by targeting one, two, or three hormones that affect blood sugar and hunger. The Tufts team added a fourth target that might improve results even more.
This approach could offer stronger and more lasting weight loss, possibly matching the effects of bariatric surgery, which is currently the gold standard for long-term weight loss but involves invasive surgery.
Normally, after eating, our bodies release hormones that help manage blood sugar and tell us when we’re full. One such hormone is GLP-1, which helps the body produce insulin and lowers blood sugar. It also slows down digestion and makes us feel full, which is why drugs like Ozempic, based on GLP-1, help with both diabetes and weight loss.
However, GLP-1 drugs are not perfect. They must be injected weekly and often cause nausea. In fact, about 40% of users stop taking them after just a month. That’s where newer drugs come in.
One example is Mounjaro (tirzepatide), which combines GLP-1 with another hormone called GIP. GIP also helps people feel full, and combining it with GLP-1 reduces the nausea side effect, making the treatment easier to stick with.
Scientists have gone even further by adding a third hormone, glucagon. Although glucagon raises blood sugar, it also increases energy use, body temperature, and reduces appetite.
When combined with GLP-1 and GIP, the glucose-raising effect of glucagon is canceled out, and all three hormones work together to boost weight loss. A drug using this triple combination, called retatrutide, is in clinical trials and has shown potential to help people lose up to 24% of their weight.
But the Tufts team didn’t stop there. They added a fourth hormone called peptide YY (PYY). PYY helps reduce appetite and slow digestion through different pathways than the other three hormones. It may also help burn fat directly.
PYY is quite different in structure, so creating a drug that includes it was challenging. The researchers solved this by joining two peptide chains end-to-end, creating a new four-in-one drug candidate.
This new drug design targets four hormone receptors at once. According to the research team, this could lead to more consistent weight loss results for more people, even those who don’t respond as well to existing treatments. It may also reduce the chances of weight gain after stopping treatment and help preserve bone and muscle mass.
While more research and clinical testing are needed, this new “tetra-functional” drug candidate could move us closer to the weight loss results seen with bariatric surgery—without the need for surgery.
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 information 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 the Journal of the American Chemical Society.
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