The best drugs for obesity are not yet there

Ozempic is just the beginning of a new era of obesity treatment. A review published this week anticipates the emergence of similar experimental drugs that will probably 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 original body weight in trials so far.

Semaglutide is a synthetic, 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 as Wegovy. It is far from the first GLP-1 drug to reach the public, but semaglutide has been a game changer for the treatment of obesity. It has been shown to help people lose between 10% and 15% of their weight in studies, well above the typical success seen with diet and exercise alone and even surpassing the typical results of GLP drugs -1 more ancient.

Semaglutide is not the only new kid on the block, however. by Eli Lilly tirzepatide it mimics both GLP-1 and another hunger-related hormone called GIP—a potent 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, some of which have undergone human testing and are ready to overshadow even tirzepatide.

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

As expected, they found that currently approved drugs were generally safe and effective, with tirzepatide doing the best currently (participants lost up to 17% of their body weight after 72 weeks of therapy). But they also identified retatrutide as performing even 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, of the 12 GLP-1 (drugs) identified by our research, the greatest mean reduction in body weight was reported in randomized controlled trials of retatrutide, tirzepatide and semaglutide,” the researchers wrote in his document. published Tuesday in the Annals of Internal Medicine.

Retatrutide is developed by Eli Lilly, and now it has been tested in phase 3 trials – trials that will reach their conclusion by 2026. And it will not be the only new arrival in the near future that could clear existing drugs d today.

Last year, for example, the first test results of the drug amycretin (developed by Novo Nordisk) suggested which could provide greater weight loss than semaglutide and tirzepatide. Other drug companies are working on their competitors to Ozempic, such as Boehringer Ingelheim and Zealand Pharma’s dual agonist. pressure cookers. Expectations have become so high that the shares of Novo Nordisk actually decreased when it announced that its drug candidate CagriSema (a mixture of semaglutide with the experimental drug cagrilintide) only helped people lose 22% of their weight in a recent trial, instead of the expected 25%.

These drugs are not free of their negatives, of course. They commonly cause gastrointestinal symptoms such as diarrhea and vomiting, and have been linked to rare but serious complications such as gastroparesis (stomach paralysis). Another major problem 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 growing demand fueled a gray 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 drugs related to GLP-1 will help limit some of these problems, especially cost and insurance coverage. If that actually happens, we’ll see. But it is almost certain that there will be many drugs for the current crown of semaglutide and tirzepatide as the best obesity treatments around.