Scientists test 4-in-1 drug that may rival Ozempic and bariatric surgery

Researchers explore next-gen obesity drug targeting four hormones at once to overcome limits of existing treatments

Obesity, a condition affecting millions globally, is associated with diabetes, heart disease, cancer and other chronic illnesses. What if a single pill could help address all of these, with fewer side effects?

 

Scientists at Tufts University, US, have developed a new drug candidate that activates four different hormone receptors at once, offering a potentially more powerful and safer treatment for obesity and related conditions.

 

In a study titled Molecular design of unimolecular tetra-receptor agonists, published in the Journal of the American Chemical Society, Tufts chemists describe a drug that combines four hormones into one. They claim it could outperform currently available weight loss drugs like Ozempic and Wegovy, with fewer side effects.

 

 

The therapy is expected to not only help people shed weight but also tackle obesity-related conditions such as type 2 diabetes, cardiovascular disease, and even certain cancers.

Why do current weight loss drugs fall short?

Popular drugs such as Ozempic and Wegovy are based on a single hormone—GLP-1 (glucagon-like peptide-1)—which helps control blood sugar, slows digestion, and increases satiety. That’s why they are widely used in diabetes and weight management.

 

But, according to the Tufts study, these treatments have notable drawbacks: 

• They require weekly injections, which some patients find inconvenient
• Many users discontinue use within a month due to severe nausea
• Weight is often regained after the drug is stopped
• Long-term concerns include loss of muscle and bone density 

What’s new about the Tufts University approach?

Instead of relying on just one hormone, the Tufts team created a drug that activates four powerful metabolic hormone receptors simultaneously. The hormones include: 

• GLP-1: Controls blood sugar and appetite 
• GIP (glucose-dependent insulinotropic peptide): Enhances satiety and reduces nausea when combined with GLP-1 
• Glucagon: Boosts calorie burning, suppresses appetite, increases energy use 
• Peptide YY (PYY): Slows digestion, reduces hunger, and may aid in fat burning

 

By merging elements of all four, researchers developed a tetra-functional drug candidate that can stimulate four hormone pathways at once.

Could this outperform Ozempic and Mounjaro?

According to the study, that’s the goal. Existing triple-hormone drugs such as retatrudide (still in trials) have already shown weight loss of up to 24 per cent of body weight, compared to 6–15 per cent with older GLP-1-only drugs.

 

The Tufts team believes their four-hormone design could approach the weight-loss potential of bariatric surgery, which typically results in 30 per cent or more body weight loss—without the invasiveness or surgical risks.

 

“By hitting four different hormone receptors at the same time, we hope to deliver more consistent and lasting results,” said Martin Beinborn, visiting scholar and study co-author, in a university statement.

How could this change obesity treatment?

If clinical trials succeed, this drug could go far beyond weight loss alone. Obesity is linked to more than 180 health conditions, including cancer, liver damage, and heart disease.

 

Researchers also believe the drug may help preserve muscle and bone mass, a key concern with current GLP-1-based treatments. Early findings suggest it could also delay or reduce weight regain after discontinuation.

What happens next?

The four-in-one drug remains experimental and will require years of testing before it becomes publicly available. But scientists are optimistic.

 

“This is about designing a single drug that not only treats obesity but also helps prevent the long list of diseases linked to it,” said Professor Krishna Kumar in the statement.

 

For the millions living with obesity, and those struggling with the limitations of current medications, this breakthrough could usher in a new generation of treatments. 

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