Ozempic is just the beginning of a new era of obesity treatment. A review published this week previews the emergence of similar experimental drugs that are likely to be more effective in helping people lose weight.
Researchers at McGill University conducted the study, which was a review of clinical trial data surrounding GLP-1 drugs such as semaglutide (the active ingredient in Ozempic and Wegovy). Researchers have reaffirmed the safety and effectiveness of today's drugs. But they also highlighted the potential efficacy of newer compounds currently under development such as retatrutide, which has helped people lose more than 20% of their original body weight in trials now.
Semaglutide is a synthetic, longer-lasting version of the hormone GLP-1—a hormone that regulates hunger and insulin production, among other things. Developed by Novo Nordisk, semaglutide was first approved for type 2 diabetes in 2017 as Ozempic, then for obesity in 2021 as Wegovy. It was far from the first GLP-1 drug to reach the public, but semaglutide became a game-changer for the treatment of obesity. It has been shown to help people lose between 10% to 15% of their weight in studies, which is more than the usual success seen with diet and exercise alone and more than the usual result of older GLP-1 drugs.
Semaglutide isn't the only new kid on the block, though. to Eli Lilly tirzepatide mimics GLP-1 and another hunger-related hormone called GIP—a powerful combination that allowed it to dethrone semaglutide. In clinical trials, people on tirzepatide lost up to 20% of their baseline weight. There are dozens of other related obesity treatments in the pipeline as well, some of which have made it to human trials and are poised to surpass even tirzepatide.
McGill researchers analyzed data from 26 randomized clinical trials of single-agent GLP-1 drugs, double agonists like tirzepatide, and even triple-agonist drugs like retatrutide, which combine the synthetic versions of three hunger-related hormones: GLP-1, GIP, and glucagon. These trials involved people living with obesity but without type 2 diabetes.
As expected, they found that currently approved drugs are generally safe and effective, with tirzepatide the best so far (participants lost up to 17% of their body weight after 72 weeks of therapy). But they also singled out retatrutide as performing better in a shorter period of time, with participants losing up to 22% of their body weight after just 48 weeks of therapy.
“We found that, at 12 GLP-1 [drugs] identified by our search, the largest mean body weight reductions were reported in randomized controlled trials of retatrutide, tirzepatide, and semaglutide,” the researchers wrote in their paper, published Tuesday at Annals of Internal Medicine.
Retatrutide was developed by Eli Lilly, and it's currently being tested in phase 3 trials—trials that will reach their conclusion in 2026. And it's not the only newcomer coming in the near future that could beat out existing drugs today .
Last year, for example, the results of early trials of the drug amycretin (developed by Novo Nordisk) suggested that it may provide greater weight loss than semaglutide and tirzepatide. Other drug companies are working on their own competitors with Ozempic, such as Boehringer Ingelheim and Zealand Pharma's dual agonist pressure cookers. Expectations made Novo Nordisk's stock very high really come down when it announced that their drug candidate CagriSema (a mix of semaglutide with the experimental drug cagrilintide) only helped people lose 22% of their weight in a recent trial, instead of the 25% expected.
These drugs are not free of their negatives, of course. They usually cause gastrointestinal symptoms such as diarrhea and vomiting, and have been associated with rare but serious complications such as gastroparesis (stomach paralysis). Another major concern is their price, with semaglutide and tirzepatide often costing about $1,000 per month without insurance coverage (which is often not provided by private and public insurers). That cost and increased demand fueled a gray and black market for these drugs, people turn to cheaper, but less safe compounded and fake versions.
Some experts hope that the arrival of more GLP-1-related drugs will help reduce some of these issues, particularly cost and insurance coverage. If that actually happens, we'll have to see. But there will almost certainly be multiple drugs for the current crown of semaglutide and tirzepatide as the best obesity treatments around.
