Scientists reveal pill that helps shed 20% of body weight

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Abstract

A new kind of weight-loss medicine is making waves in medical research — Orforglipron, the first small-molecule, nonpeptide oral GLP-1 receptor agonist. Unlike existing GLP-1 drugs that require injections, this one comes as a pill. In a major phase 3 trial, it showed remarkable success in helping people with obesity lose weight safely and consistently.

Orforglipron represents a new era in obesity treatment — an oral GLP-1 receptor agonist that delivers powerful weight-loss results without injections. In clinical trials, it helped participants lose up to 11% of their body weight while improving blood pressure and metabolic health.
Photo by Diana Polekhina on Unsplash

Background

Obesity isn’t just about appearance — it’s a complex health issue that affects the heart, metabolism, and even mental well-being. Diet and exercise remain the cornerstones of treatment, but for many, they’re not enough. Over the last few years, injectable GLP-1 drugs like semaglutide have helped millions lose weight by suppressing appetite and improving how the body processes sugar and fat.

But injections can be inconvenient and intimidating. Orforglipron changes that. It’s a once-daily pill that works through the same biological pathway — activating the GLP-1 receptor to control hunger and improve metabolism — but without needles. It’s designed to make long-term weight management easier and more sustainable.

The Study

In this 72-week phase 3 clinical trial, researchers studied over 3,100 adults with obesity but without diabetes. Participants were randomly assigned to receive either Orforglipron (6 mg, 12 mg, or 36 mg) or a placebo. Everyone followed a healthy diet and exercise plan.

The main question was simple: how much weight could people lose over 72 weeks?

Results

The results were striking. Those who took Orforglipron lost significantly more weight than those on placebo. At the highest dose — 36 mg — participants shed an average of 11% of their body weight, compared to just 2% in the placebo group.

More than half of the people taking 36 mg lost at least 10% of their weight, and nearly one in five achieved 20% or more — a result that rivals or even surpasses many injectable treatments.

But it wasn’t just the scale that changed. Waist circumference, blood pressure, triglycerides, and non-HDL cholesterol levels all improved. These results point to real metabolic health gains, not just cosmetic changes.

Safety and Side Effects

Like most GLP-1-based treatments, Orforglipron came with a few mild downsides. The most common were nausea, vomiting, and diarrhea — usually mild to moderate and temporary. Around 5–10% of participants stopped treatment because of side effects, compared to 3% in the placebo group. Overall, the drug’s safety profile was reassuring and consistent with other GLP-1 medicines.

Conclusion

For people living with obesity, Orforglipron could be a genuine breakthrough. Over 72 weeks, it produced meaningful, lasting weight loss and measurable health improvements — all in a simple, once-daily pill.

As research continues, this oral GLP-1 drug might soon make effective obesity treatment more accessible and practical than ever before. If approved, it could open the door to a new era of weight management — one that’s powerful, convenient, and truly life-changing.

Trial Name: ATTAIN-1 | Funded by: Eli Lilly | ClinicalTrials.gov: NCT05869903

Citation: Wharton S, Aronne LJ, et al. N Engl J Med. 2025; doi:10.1056/NEJMoa2511774. Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist for Obesity Treatment.

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