Consider taking Ozempic but worried about losing too much muscle? New clinical trial data may point to a future that is no longer focused.
Regeneron Pharmaceuticals announced on Monday the interim results of its Phase 2 Courage trial, which tested a combination of semaglutide, an active ingredient in the popular drugs Ozempic and Wegovy, and up to two antibodies designed to preserve muscle. Compared to those who only took semaglutide, the combination lost the weight loss and even seemed to lose weight. These findings will pave the way for large-scale trials of these drugs.
Semaglutide and similar GLP-1 drugs have been shown to be highly effective in obesity and type 2 diabetes treatment. But, like every drug, they may weigh trade-offs, including muscle loss.
Experts rightly believe that this side effect is not really unique to GLP-1. Whenever we lose weight, we can lose fat and fat-free mass, also known as lean body weight. To date, studies have not demonstrated whether the loss of lean body weight when taking GLP-1 can be associated with any actual health problems.
That is, some clinical trial data show that people who take semaglutide may lose muscles than other means of losing weight (the proportion of lean body weight is lost, while the proportion of weight loss reaches 40%). Moreover, some populations are more susceptible to complications of losing too much muscle, such as older people. So while the health risks of this impact are unclear, doctors and pharmaceutical companies have begun looking for ways to mitigate this.
Regeneron’s strategy relies on two experimental lab-made antibodies, Trevogrumab and Garetosmab. Both antibodies are associated with separate proteins that play a key role in limiting skeletal muscle growth. Trevogrumab blocks myostatin, also known as GDF8, while GaretoSmab blocks ActivinA. These drugs have been studied as a treatment for certain muscle or bone-related diseases, but Regeneron believes they can also be used to actively prevent muscle loss when taking GLP-1.
The company’s second phase of the trial involved approximately 600 people obesity. During the first half of the trial (26 weeks), volunteers were divided into four groups: only semi-violetglutide was given, two groups were given semi-ciguate and lower or higher doses of trevogrumab, while one in four gave all three drugs at the same time.
By week 26, people who only took Semaglutide lost about 35% of their lean body weight, according to the company. People taking all three medications also lost the most weight (about 10% compared to the baseline compared to the other groups).
“These early insights from the courage trial… clearly identify the principle that prevents GDF8 with or without activin A can retain muscle and further increase fat loss in patients treated with GLP-1 treatment, thereby improving the mass of weight loss.
These results have not been reviewed by outside scientists and the second half of the trial has not been fully analyzed (testing whether trevogrumab alone can improve weight maintenance). People taking higher doses of trevogrumab or the entire tri-drug combination also reported greater adverse effects and exited the study at a higher rate, suggesting that this combination strategy is not without its own shortcomings. Finally, these are still the early days of the company’s novel weight loss approach.
Many people are concerned about potential muscle loss when taking GLP-1, so there seems to be a drug audience willing to reduce this risk. Regeneron is not the only company or research team trying to find a solution for this. So, as impressive as Ozempic and its kind, they can still be improved further.
