Achieving a healthy weight could become more and more attainable as time goes on
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The past few years have seen the emergence of highly effective drugs for treating obesity, and the hope is that the experimental treatments on trial in 2026 will prove to be even more effective.
“We are witnessing an exciting new chapter in obesity treatment that is improving the health and lives of many patients,” says Lora Heisler at 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 per cent drop in body weight can lower those risks.”
The first of the blockbuster weight-loss drugs was a small protein called semaglutide. It was approved in 2017 as a diabetes treatment, marketed as Ozempic. In 2021, it was also approved for weight loss, sold as 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 turned out to have direct cardiovascular benefits, in addition to the benefits due to weight loss, and may also help treat other conditions, such as drug and alcohol addictions. However, semaglutide can have side effects, including nausea and vomiting, that result in many people discontinuing its use.
In 2023, another drug called tirzepatide (sold as Mounjaro for diabetes) was also approved for weight loss, marketed as Zepbound. Tirzepatide improves on semaglutide by having a dual action: it mimics both GLP-1 and another hormone called GIP, which is involved in regulating energy use and storage. It has similar side effects to semaglutide.
In a head-to-head trial, semaglutide reduced people’s weight by 14 per cent, on average, over 72 weeks, whereas tirzepatide reduced it by 20 per cent. Other studies show that lost weight is typically regained if the drugs are discontinued.
Coming up next are more dual-action, and even triple-action, drugs. 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 3400 adults, people on CagriSema lost 20 per cent of their weight after 68 weeks, compared with 15 per cent for semaglutide alone and 12 per cent for cagrilintide alone. That suggests it is on par with tirzepatide, though various trials are continuing.
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 the GLP-1 and amylin receptors, rather than two molecules.
In a small early trial of amycretin with just 125 participants, people lost 24 per cent 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-stage trial starting only in 2026.
Then there’s the “triple G” drug retatrutide, which mimics three hormones: GLP-1, GIP and glucagon, which triggers the release of fat stores. In a trial with 338 people, those on the highest dose lost 24 per cent of their weight, on average, after 48 weeks. Again, that is promising but much depends on the results of the final-stage trials already under way. It’s possible retatrutide could be approved in late in 2026, but it might be later.
It should be noted that the figures for weight loss from different trials are not directly comparable because of differences in, say, how participants were selected, as well as duration and dosing. The averages also obscure the wide variation in people’s response to GLP-1 drugs: some don’t respond at all whereas other see dramatic weight loss.
Beyond 2026, more than 100 weight-loss drugs are in development as pharmaceutical companies race to get a slice of the lucrative market. Many target various combinations of the existing four targets – the GLP-1, GIP, glucagon and amylin receptors – but some involve different targets and mechanisms.
Others try to compensate for undesirable effects, such as the fact that some of the weight people shed on GLP-1 drugs is due to muscle loss rather than fat loss. For instance, a trial that finished earlier this year combined semaglutide with bimagrumab, which blocks a receptor that inhibits muscle growth, though the results have yet to be announced.
“What is really exciting is that there are more promising drugs on the horizon that could produce even greater benefit with fewer side effects,” says Heisler.
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