The best obesity drugs aren’t even here yet

Ozempic is just the beginning of a new era in the treatment of obesity. A review published this week predicts the emergence of similar experimental drugs that are likely to be even more effective in helping people lose weight.

McGill University researchers 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 superiority of newer compounds currently in development, such as retatrutide, which has helped people lose more than 20% of their initial body weight in trials so far.

semaglutide is a synthetic and longer-lasting version of the GLP-1 hormone, 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. like Wegovy. It’s far from the first GLP-1 drug to reach the public, but semaglutide has changed the rules for treating obesity. It has been shown to help people lose anywhere between 10% to 15% of their weight in studies, well above the typical success seen with diet and exercise alone, and even surpasses the typical results of older GLP-1 drugs.

Semaglutide isn’t the only new kid on the block, though. To Eli Lilly tirzepatide mimics both GLP-1 and another hunger-related hormone called GIP—a powerful combination that allows 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, some of which have reached human testing and are poised to eclipse even tirzepatide.

McGill researchers analyzed data from 26 randomized clinical trials of single-agent GLP-1 drugs, dual agonists such as tirzepatide, and even triple agonist drugs such as retatrutide, which combines synthetic versions of three hunger-related hormones: GLP-1, GIP, and glucagon. These studies included people living with obesity but who did not have type 2 diabetes.

As expected, they found that the drugs approved today were generally safe and effective, with tirzepatide faring best (participants lost up to 17% of body weight after 72 weeks of therapy). But they also touted retatrutide as even better over a shorter period of time, with participants losing up to 22% of their body weight after just 48 weeks of therapy.

“We found that of the 12 GLP-1 (drugs) identified in our search, the greatest mean reductions in body weight 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 is being developed by Eli Lilly and is currently being tested in phase 3 trials – trials that will end by 2026. And it will not be the only newcomer in the near future that could overtake the drugs that exist today.

Last year, for example, the results of early studies of the drug amicretin (developed by Novo Nordisk) suggested that it may provide greater weight loss than semaglutide and tirzepatide. Other pharmaceutical companies are working on their own competitors to Ozempic, such as Boehringer Ingelheim and Zealand Pharma’s dual agonist pressure cookers. Expectations became so high that shares of Novo Nordisk actually dropped when it announced that their drug candidate CagriSema (a mixture of semaglutide with the experimental drug cagrilintide) only helped people lose 22% of their weight in a recent study, instead of the expected 25%.

These drugs are not without their negatives, of course. They usually cause gastrointestinal symptoms such as diarrhea and vomiting and are associated with rare but serious complications such as gastroparesis (gastric paralysis). Another major concern is their cost, with semaglutide and tirzepatide often costing about $1,000 a month without insurance coverage (which is often not provided by private and public insurers). This price and rising demand have fueled a gray and black market for these drugs, with people turning to cheaper but less safe mixed and fake versions.

Some experts hope that the arrival of more GLP-1-related drugs will help limit some of these problems, particularly cost and insurance coverage. Whether that will actually happen remains to be seen. But it is almost certain that there will be many drugs for semaglutide and tirzepatide’s current crown as the best obesity treatments.