GLP-1 drugs like semaglutide (Ozempic and Wegovy) have finally started to make weight loss a sustainable reality for many people with obesity. The ceiling of obesity treatment hasn’t been reached yet, however, and muscle-building drugs might be able to supercharge GLP-1s, research out this week suggests.
This week, researchers at Eli Lilly and others published the results of a phase II trial that paired semaglutide with bimagrumab, an experimental antibody developed to prevent muscle loss. Compared to semaglutide alone, people on the two-drug combo lost significantly more weight and fat while holding onto more lean body mass. Though muscle loss isn’t a major concern for most people on GLP-1s, bimagrumab and similar treatments could possibly become potent add-ons should these results bear out in future studies.
“These findings support further development of bimagrumab, alone or in combination with incretin therapy, to achieve optimal weight loss,” the researchers wrote in their paper, published Monday in Nature Medicine.
Two better than one?
When people with obesity lose weight, they lose both fat and lean body mass, the latter of which can include some muscle. Proportionally, people usually shed much more fat than lean body mass, so the ratio actually improves. Weight loss is also typically associated with improved physical functioning, even if some muscle is lost.
Some studies have suggested that people taking GLP-1s might lose slightly more lean body mass than usual. This has led to people fearmongering that GLP-1s are dangerously sapping away people’s muscles—a claim with next to no evidence. That said, there are populations who might be more vulnerable to losing muscle while taking GLP-1s, such as older adults. So several drug companies have started to work on ways to blunt the potential impact of muscle loss.
Eli Lilly acquired bimagrumab from Novartis and has been developing it as a treatment for muscle-wasting conditions and obesity. It’s a lab-made antibody designed to inhibit activin receptor type-2B, a protein that regulates muscle mass by limiting its growth. In this latest trial of roughly 500 people with obesity, the volunteers were broadly randomized into four groups: those taking a placebo, those on bimagrumab alone, those only on semaglutide, and those taking both.
Over the course of 48 weeks, people on the highest dose of semaglutide and bimagrumab lost up to 20% of their body weight, whereas people on the highest dose of semaglutide alone lost up to 15% of their body weight (results in line with other clinical trials). By week 72, the combination group also lost proportionally more fat than the semaglutide-only group (a 45.7% decrease compared to 27.8%), and they lost less lean body mass (a loss of 2.9% from baseline vs 7.4%).
The combination therapy also appeared to be generally safe and tolerable, with the safety profile in line with what’s known for both classes. These included gastrointestinal symptoms like nausea for semaglutide and muscle cramps for bimagrumab.
The future of combination treatment
To reiterate, there’s little evidence GLP-1s are ruining the muscles of users, at least any more than losing weight generally does. Even if people are worried about muscle loss on these drugs, they don’t need experimental antibodies to mitigate its impact. Resistance training and increasing your protein intake are proven ways to maintain a healthy amount of muscle mass while losing weight, for instance.
“Musclezempic” might still be helpful for obese people at higher risk for concerning muscle loss, though. Boosting the potential amount of weight and fat lost from GLP-1 therapy could also make the combination a more appealing option for some. And bimagrumab alone could be a viable obesity treatment (in the trial, people on the highest dose lost up to 10% body weight).
Eli Lilly is already moving ahead with a phase II trial of bimagrumab with its own obesity drug tirzepatide (Zepbound and Mounjaro), the latter of which is generally more effective than semaglutide. And it’s not the only company studying these combination treatments. So this research might only signal the beginning of a new approach to weight loss.
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