The weight-loss drugs on trial in 2026 may trump Ozempic and Zepbound

Recent years have seen the emergence of highly effective drugs to treat obesity, and the hope is that experimental treatments tested in 2026 will prove even more effective.

“We are seeing an exciting new chapter in the treatment of obesity that is improving the health and lives of many patients,” says Lora Heisler from the University of Aberdeen, UK. “Obesity fuels some of the world’s most serious diseases: cancer, heart disease and type 2 diabetes. Even a modest 5% weight loss can reduce these risks.”

The first of the successful weight loss drugs was a small protein called semaglutide. It was approved in 2017 as a treatment for diabetes, marketed under the name Ozempic. In 2021, it was also approved for weight loss, sold under the name Wegovy.

Semaglutide mimics the action of a natural hormone called GLP-1 by binding to receptors in the brain and pancreas, reducing people’s appetite and slowing the passage of food through the stomach. It has also been shown to have direct cardiovascular benefits, in addition to benefits due to weight loss, and may also help treat other conditions, such as drug and alcohol addiction. However, semaglutide can have side effects, including nausea and vomiting, which cause many people to discontinue its use.

In 2023, another drug called tirzepatide (sold as Mounjaro for diabetes) was also approved for weight loss, marketed as Zepbound. Tirzepatide enhances semaglutide by having a dual action: it mimics both GLP-1 and another hormone called GIP, which is involved in regulating energy consumption and storage. It has side effects similar to semaglutide.

In a comparative trial, semaglutide reduced people’s weight by 14 percent on average over 72 weeks, while tirzepatide reduced it by 20 percent. Other studies show that the weight lost is usually regained if the medications are stopped.

Next come more drugs with double or even triple action. One that could be approved next year is CagriSema, a combination of a drug called cagrilintide – which makes people feel full by mimicking the action of a hormone called amylin – with semaglutide.

In a trial involving more than 3,400 adults, people taking CagriSema lost 20 percent of their weight after 68 weeks, compared to 15 percent for semaglutide alone and 12 percent for cagrilintide alone. This suggests that it is comparable to tirzepatide, although various trials are underway.

A similar drug called amycretin is also in development. Like CagriSema, amycretin mimics both GLP-1 and amylin, but it consists of a single molecule that can bind to both GLP-1 and amylin receptors, rather than two molecules.

In a small, preliminary trial of amycretin with just 125 participants, people lost 24% of their weight on average after 36 weeks. This suggests it might be better than tirzepatide, but it will be some time before this becomes clearer, with a final trial not starting until 2026.

Then there’s retatrutide, a “triple G” drug, which mimics three hormones: GLP-1, GIP, and glucagon, which triggers the release of fat stores. In a trial of 338 people, those who received the highest dose lost an average of 24 percent of their weight after 48 weeks. Again, this is promising, but much depends on the results of final trials already underway. It is possible that retatrutide will be approved in late 2026, but it may be later.

It should be noted that weight loss figures from the different trials are not directly comparable due to differences, for example in how participants were selected, as well as duration and dosage. The averages also mask the wide variation in people’s response to GLP-1 drugs: Some don’t respond to them at all while others see dramatic weight loss.

Beyond 2026, more than 100 weight-loss drugs are in development as pharmaceutical companies race to capture a share of this lucrative market. Many target various combinations of the four existing targets – GLP-1, GIP, glucagon and amylin receptors – but some involve different targets and mechanisms.

Others attempt to compensate for side effects, such as the fact that some of the weight lost on GLP-1 drugs is due to muscle loss rather than fat loss. For example, a trial completed earlier this year combined semaglutide with bimagrumab, which blocks a receptor that inhibits muscle growth, although the results have not yet been announced.

“What’s really exciting is that there are more promising drugs on the horizon that could produce even greater benefits with fewer side effects,” Heisler says.