The best obesity drugs aren’t even here yet
A review published this week previews the emergence of similar experimental drugs that will likely be even more effective at helping people lose weight. 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). Researchers reaffirmed that today’s drugs are safe and effective. 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. Novo Nordisk developed semaglutide, which was approved by the FDA for obesity and type 2 diabetes as Wegovy in 2021. Semaglutide is not the first GLP-1 to be approved by the FDA, but it has changed the way obesity is treated. 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 GLP-1 as well as another hunger-related hormonal called GIP. This powerful combination has allowed it dethroned semaglutide. There are dozens of other obesity treatments in the pipeline, some of which have made it to human testing and will soon overshadow tirzepatide. 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. The McGill researchers found that the approved drugs are generally effective and safe, but tirzepatide is currently the most successful (participants lose up to 17% of their 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
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. It won’t even be the only drug that will outperform today’s current drugs in the future. Boehringer Ingelheim’s dual-agonist survodutide and Zealand Pharma are both working on Ozempic competitors. 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.[drugs]These drugs aren’t free of its negatives, of course. These drugs can cause diarrhea, vomiting and other gastrointestinal problems. They have also been linked to serious but rare complications such as gastroparesis. Semaglutide and Tirzepatide can cost up to $1,000 a month without insurance (which is often not provided by public or private 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. We’ll see if that happens. It’s almost certain, however, that semaglutide will soon be challenged by a number of other drugs to take the current title as best treatment for obesity held by tirzepatide.
