Ozempic Without Muscle Loss? New Drug Combo Trial Finds It's Possible

Gizmodo

04-06-2025

Thinking about taking Ozempic but worried about losing too much muscle? New clinical trial data might point to a future where that's no longer a concern.
Regeneron Pharmaceuticals announced the interim results of its Phase 2 COURAGE trial Monday, which tested a combination of semaglutide (the active ingredient in popular drugs Ozempic and Wegovy) and up to two antibodies designed to preserve muscle. Compared to people who only took semaglutide, those on the combination lost less lean mass and even appeared to shed a bit more weight. The findings will pave the way for larger trials of these drugs.
Semaglutide and similar GLP-1 drugs have proven to be highly effective obesity and type 2 diabetes treatments. But like every drug, they have their possible trade-offs, including muscle loss.
Experts have correctly argued that this side effect isn't truly unique to GLP-1s. Anytime we lose a significant amount of weight, we're likely to lose both fat and fat-free mass, also known as lean body mass. And research to date hasn't shown whether the lean body mass lost while taking GLP-1s can be linked to any actual health issues.
That said, some clinical trial data has suggested that people taking semaglutide in particular can lose a bit more muscle than they might losing weight through other means (the proportion of lean body mass lost while losing weight has reached up to 40%). And there are certain populations more vulnerable to complications from losing too much muscle, such as older adults. So while the health risks of this effect aren't clear, doctors and drug companies have started to look for ways to mitigate it.
Regeneron's strategy relies on two experimental lab-made antibodies, trevogrumab and garetosmab. Both antibodies are linked to separate proteins that play key roles in limiting skeletal muscle growth. Trevogrumab blocks myostatin, also known as GDF8, and garetosmab blocks activin A. The drugs are already being investigated as treatments for certain muscle- or bone-related conditions, but Regeneron reasoned that they could also be used to proactively prevent muscle loss while taking a GLP-1.
The company's Phase 2 trial involved around 600 people with obesity. For the first half of the trial (26 weeks), the volunteers were divided into four groups: one group only given semaglutide, two groups given semaglutide and a lower or higher dose of trevogrumab, and a fourth given all three drugs at once.
According to the company, people taking only semaglutide lost about 35% of their lean body mass by week 26. Those who took semaglutide with trevogrumab lost around 17%, while people on the full combination saw just a 7% loss. People taking all three drugs also lost the most weight (13% from their baseline compared to roughly 10% for the other groups).
'These early insights from the COURAGE trial…clearly establish the principle that blocking GDF8 with or without activin A can preserve muscle and further increase fat loss in patients being treated with GLP-1 therapy, thereby improving the quality of weight loss,' said George Yancopoulos, president and chief scientific officer at Regeneron, in a statement from the company.
These results have yet to be vetted by outside scientists, and the data from the second half of the trial hasn't been fully analyzed (testing if trevogrumab alone can improve weight maintenance). People taking a higher dose of trevogrumab or the full three-drug combination also reported more adverse effects and dropped out of the study at a higher rate, suggesting that this combination strategy isn't without its own disadvantages. In the end, these are still early days for the company's novel approach to weight loss.
Plenty of people are worried about the potential loss of muscle while taking GLP-1s, so there seems to be a willing audience for medications that can reduce this risk. And Regeneron isn't the only company or research team trying to find a workaround for it. So as impressive as Ozempic and its ilk have been, they can still be further improved.