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 will likely be even more effective at helping people lose weight.
Researchers at McGill University conducted the study, which was a review of the clinical trial data surrounding GLP-1 drugs like semaglutide (the active ingredient in Ozempic and Wegovy). The researchers reaffirmed the safety and effectiveness of today’s drugs. But they also highlighted the potential superiority of newer compounds currently under development such as retatrutide, which has helped people lose more than 20% of their original body weight in trials so far.
Semaglutide is a synthetic and 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’s far from the first GLP-1 drug to reach the public, but semaglutide has been a game-changer for obesity treatment. It’s been shown to help people lose somewhere between 10% to 15% of their weight in studies, well above the typical success seen with diet and exercise alone and even surpassing the typical results of older GLP-1 drugs.
Semaglutide isn’t the only new kid on the block, though. Eli Lilly’s tirzepatide mimics both GLP-1 and another hunger-related hormone called GIP—a potent combination that has allowed it to dethrone semaglutide. In clinical trials, people on tirzepatide have lost as much as 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 testing and are poised to overshadow even tirzepatide.
The 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 combines synthetic versions of three hunger-related hormones: GLP-1, GIP, and the glucagon. These trials involved people living with obesity but who did not have type 2 diabetes.
As expected, they found that today’s approved drugs were generally safe and effective, with tirzepatide faring the best currently (participants lost up to 17% body weight after 72 weeks of therapy). But they also singled out retatrutide as performing even better in a shorter period of time, with participants losing up to 22% of their body weight after only 48 weeks of therapy.
“We found that, of the 12 GLP-1 [drugs] identified by our search, the greatest mean body weight reduction was reported in randomized controlled trials of retatrutide, tirzepatide, and semaglutide,” the researchers wrote in their paper, published Tuesday in the Annals of Internal Medicine.
Retatrutide is being developed by Eli Lilly, and it’s now currently being tested in phase 3 trials—trials that will reach their conclusion by 2026. And it won’t be the only newcomer arriving in the near-future that could outslug today’s existing drugs.
Last year, for instance, early trial results of the drug amycretin (developed by Novo Nordisk) suggested that it could provide greater weight loss than semaglutide and tirzepatide. Other drug companies are working on their own competitors to Ozempic, such as Boehringer Ingelheim and Zealand Pharma’s dual agonist survodutide. Expectations have gotten so high that Novo Nordisk’s stock actually dropped when it announced that their drug candidate CagriSema (a mix of semaglutide with the experimental drug cagrilintide) only helped people lose 22% weight in a recent trial, rather than the 25% expected.
These drugs aren’t free of its negatives, of course. They commonly cause gastrointestinal symptoms such as diarrhea and vomiting, and have been tied to rare but serious complications like gastroparesis (stomach paralysis). Another major concern is their price, with semaglutide and tirzepatide often costing around $1,000 per month without insurance coverage (which often isn’t provided by private and public insurers). That cost and surging demand has fueled a grey and black market for these drugs, with people turning to cheaper, but less safe compounded and counterfeit versions.
Some experts hope that the arrival of more GLP-1 related drugs will help curtail some of these issues, particularly cost and insurance coverage. Whether that actually happens, we’ll have to see. But it’s almost certain that there will be plenty of drugs coming for semaglutide and tirzepatide’s current crown as the best obesity treatments around.
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