Scientists Create a Promising 4-in-1 Weight Loss Drug

Imagine if one single medicine could help you lose weight, reduce your appetite, manage your blood sugar, and lower the risk of several chronic diseases—all while avoiding some of the most frustrating side effects of current treatments.

That’s exactly what researchers at Tufts University are aiming for with their newly designed 4-in-1 weight loss drug.

Why This Matters

Right now, more than 15 million adults in the U.S. are prescribed medications like Ozempic and Wegovy. These drugs have become incredibly popular, not just for diabetes management but also for weight loss.

The catch?

Once you stop taking them, the benefits often fade away. On top of that, many patients struggle with side effects like nausea, muscle loss, and even bone density issues. For some, these downsides are so unpleasant that they quit treatment within weeks.

The Tufts team, led by Krishna Kumar, decided to think bigger. Instead of targeting one or two hormone pathways (as current drugs do), they’ve developed a compound that activates four different hormone receptors at once.

The idea is simple but powerful: a more balanced and comprehensive approach could mean better results with fewer drawbacks.

The Science Behind It

Here’s where it gets fascinating.

Our bodies naturally release hormones after we eat to manage hunger, digestion, and energy use. Current drugs like Ozempic mimic one of these hormones, called GLP-1, which helps control blood sugar and makes us feel full.

That’s why it’s effective for weight loss—but the downside is the weekly injections and that nagging nausea.

To improve things, researchers previously combined GLP-1 with a second hormone, GIP, creating drugs like Mounjaro (also known as tirzepatide). This combo not only helped with fullness but also reduced nausea—a big win for patients. Later, scientists added a third hormone, glucagon, which paradoxically raises blood sugar but also boosts metabolism, increases energy burn, and suppresses appetite.

The result?

Even stronger weight loss effects. A drug called retatrudide, now in clinical trials, has shown weight reductions of up to 24%—far more than the 6–15% seen with earlier GLP-1-only drugs.

Now, the Tufts team has introduced a fourth hormone into the mix: peptide YY (PYY). This hormone also signals fullness and slows digestion, but through a completely different mechanism.

It might even help the body directly burn fat. By merging GLP-1, GIP, glucagon, and PYY into one single compound, the scientists have created what they call a “tetra-agonist” drug.

The Bigger Picture

Why go to all this trouble? Because the ultimate benchmark for weight loss isn’t medication at all—it’s bariatric surgery.

Surgery can reduce stomach size and lead to up to 30% body weight loss, often permanently. Current drugs don’t quite measure up, but if this new four-hormone strategy works as hoped, it might come close—without the risks and invasiveness of surgery.

Another huge benefit could be consistency across patients. With today’s treatments, some people lose a lot of weight, while others barely respond. By targeting four different receptors at once, the researchers hope to “average out” those individual differences and give more people a chance at real, lasting results.

And unlike today’s drugs, which often lead to weight regain once treatment stops, this multi-hormone approach may help preserve muscle and bone mass while keeping the pounds off for longer.

What’s Next?

The work is still in the research stage, but the concept has been published in the Journal of the American Chemical Society.

The scientists are optimistic that this design could reshape how we think about obesity treatments. After all, obesity is linked to over 180 different health conditions, from heart disease and type 2 diabetes to certain cancers and arthritis.

If a single drug could help reduce not just weight but also the risks tied to it, that would be a massive leap forward for public health.

For now, bariatric surgery remains the gold standard. But this 4-in-1 weight loss drug could represent the closest we’ve come to replicating surgery’s powerful effects—without ever stepping into an operating room.

Source: “Molecular Design of Unimolecular Tetra-Receptor Agonists” by Tristan C. Dinsmore, Jacob E. Cortigiano, Siyuan Xiang, Marina V. Spenciner, Alexandra R. Dobbins, Richard L. Zhao, Brett M. Waldman, Martin Beinborn and Krishna Kumar, 3 June 2025, Journal of the American Chemical Society.
DOI: 10.1021/jacs.5c04095