A new drug candidate targeting four appetite-related hormones could revolutionize weight loss treatment—offering greater results with fewer side effects than current therapies.
Key Points at a Glance
- Tufts scientists developed a tetra-agonist peptide that activates four distinct hormone receptors
- The drug aims to surpass the effects of Ozempic, Wegovy, and Mounjaro with less nausea
- Combines elements of GLP-1, GIP, glucagon, and PYY to reduce appetite, balance glucose, and burn fat
- Designed to approach the effectiveness of bariatric surgery in weight loss
In the escalating race to create the ultimate weight loss medication, Tufts University researchers may have just raised the bar. A new drug prototype developed by a team of chemists led by Krishna Kumar could redefine obesity treatment by combining the power of four different hormones into a single molecule—a “tetra-agonist peptide.”
Currently, over 15 million adults in the U.S. use drugs like Ozempic and Wegovy, which mimic the hormone GLP-1. These drugs work by reducing appetite and regulating glucose but come with side effects such as nausea and potential bone and muscle loss. Newer drugs like Mounjaro (tirzepatide) and the trial-stage retatrudide blend two or three hormone functions to improve outcomes and tolerability.
The Tufts team has gone a step further. Their new compound activates four different hormone receptors by combining elements of GLP-1, GIP, glucagon, and the lesser-used peptide YY (PYY). This powerful combination addresses multiple aspects of metabolism: appetite suppression, glucose balance, energy expenditure, and fat breakdown.
“Obesity is linked to over 180 diseases,” says Kumar. “We’re designing a single molecule that not only reduces weight but also lowers the risk of associated conditions like diabetes, cardiovascular disease, and even cancer.”
The challenge was enormous. PYY is structurally distinct from the other three hormones, requiring an innovative end-to-end fusion of peptide segments to retain all functionalities. But the payoff could be equally massive. Early lab models suggest this next-generation drug could approach or even match the weight loss achieved through bariatric surgery—up to 30% body weight reduction—without the need for invasive procedures.
“By targeting four hormone receptors simultaneously, we may overcome individual variability and improve average outcomes,” says Martin Beinborn, visiting scholar at Tufts and co-author of the study. That means more consistent, effective treatment across diverse patient populations.
Another critical advantage: potentially longer-lasting effects. Patients often regain weight after discontinuing current GLP-1 drugs, but multi-hormonal approaches like the tetra-agonist may extend the benefits, especially when combined with healthy lifestyle changes.
As the obesity epidemic grows and demand for weight loss medications surges, this breakthrough offers hope for a new era of treatment—one where a single, smartly designed peptide might unlock lasting metabolic transformation for millions.
Source: Tufts University
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