Adults taking semaglutide alone lost 7.4 percent of their lean mass over the course of a phase 2 trial. Adults taking semaglutide plus an experimental antibody called bimagrumab lost 2.9 percent, while losing more total weight.
That contrast, from a trial published in Nature Medicine, addresses the most persistent clinical worry about GLP-1 drugs: that a meaningful share of the weight coming off is muscle rather than fat. Up to 40 percent of weight lost on these therapies may come from lean tissue.
The finding is early. This was a phase 2 study of a drug that has not been approved for any use, and the question of whether preserved tissue translates into durable strength and function over years is not one a 72-week trial can settle.
Nine Groups, 507 Adults, 72 Weeks
The BELIEVE trial enrolled 507 adults with obesity, defined as a body mass index of at least 30, or at least 27 with one obesity related complication. Participants were randomized across nine groups.
Groups received placebo, bimagrumab at 10 or 30 milligrams per kilogram intravenously, semaglutide at 1.0 or 2.4 milligrams weekly, or combinations. The double blind treatment period ran 48 weeks, followed by an open-label extension to week 72. Bimagrumab infusions were given at weeks 4, 16, 28 and 40.
Bimagrumab is a monoclonal antibody that blocks activin type II receptors, preventing natural ligands from binding. Those receptors sit on a signaling pathway that restrains muscle growth and influences fat metabolism, so blocking them promotes skeletal muscle growth while increasing fat breakdown. The trial was registered as NCT05616013.
Fat Came Off, Muscle Largely Stayed
The published results show the combination produced weight reductions of up to 17.8 kilograms, compared with up to 14.2 kilograms for semaglutide alone.
In percentage terms, the high-dose combination produced 22.1 percent weight loss at week 72, against 15.7 percent for semaglutide alone and 10.8 percent for bimagrumab alone. Nearly 70 percent of participants on the combination reached at least a 20 percent weight reduction, compared with 25 percent on semaglutide alone.
The body composition split is the more interesting number. Roughly 92 percent of the weight lost in the high-dose combination group was fat mass, against about 72 percent with semaglutide alone. Lean mass fell 2.9 percent in the combination group, against 7.4 percent with semaglutide 2.4 milligrams alone, a statistically significant difference. Bimagrumab by itself increased lean mass by 2.5 percent.
The combination also reduced visceral fat, the deep abdominal fat most closely tied to metabolic and cardiovascular risk, by 58.2 percent against 35.8 percent with semaglutide alone, and improved markers of inflammation.
Steven Heymsfield of Pennington Biomedical Research Center, who led the analysis, has described the two drugs as working through distinct pathways, with the combination producing an additive reduction in fat mass beyond what either achieved alone.
Muscle Spasms, Acne and Laboratory Signals
Tolerability is where the picture gets more complicated, and coverage of the trial has tended to skip it.
Muscle spasms and acne were prominent among participants receiving bimagrumab, while gastrointestinal intolerance and fatigue tracked with semaglutide, as expected. Discontinuations were highest in the bimagrumab monotherapy arms. Heymsfield has also noted temporary increases in LDL cholesterol among the safety findings. No deaths were reported.
Activin receptor biology is complex, and some safety issues surface only when large numbers of people take a drug for long periods, which is what phase 3 trials and post-market surveillance exist to detect.
Funding and interests should be on the record. The study was funded by Versanis Bio, which was acquired by Eli Lilly during the trial. Semaglutide is made by Lilly's competitor Novo Nordisk, an unusual pairing that traces to that acquisition.
Strength and Function Over Time Remain the Open Question
Lean mass measured by imaging is a proxy. It is not the same as grip strength, walking speed, stair climbing ability, or the capacity to get out of a chair, and those are the outcomes that determine whether muscle loss during weight loss actually harms someone.
Investigators presenting the trial reported improvement in physical function alongside the body composition findings, so it is not accurate to say function was ignored. What has not been established is whether that advantage holds over years, in a wider population, and after treatment stops. A 32-week treatment withdrawal period was still underway when the results were presented, according to Healio.
Several other limits apply. Bimagrumab was given intravenously in this trial, a delivery route with real practical burden. A trial combining bimagrumab with tirzepatide, Lilly's own drug, is underway.
None of this is available to patients. Bimagrumab is investigational, has not been approved by the FDA for any indication, and cannot be prescribed for weight loss.
Steps Available to Patients on GLP-1 Drugs Now
People currently taking a GLP-1 medication and concerned about muscle loss do have evidence-based options, none of which involve waiting for an antibody.
Resistance training and adequate protein intake during weight loss are the interventions with the strongest support for preserving lean tissue. Anyone on one of these medications, particularly adults over 60, should raise the question at their next appointment and ask whether a referral to a dietitian or physical therapist makes sense.
No one should stop or change a prescribed medication based on a phase 2 trial. Rapid weight loss without attention to strength carries its own risks, especially for older adults where falls become the downstream concern.
The next milestones to watch are results from the tirzepatide combination trials and any decision to advance bimagrumab into phase 3.
Frequently Asked Questions
Can I get bimagrumab? No. It is investigational and has not been approved by the FDA for any use, including weight loss.
How much muscle do people lose on GLP-1 drugs? Up to 40 percent of total weight lost may come from lean tissue. In this trial, semaglutide 2.4 milligrams alone reduced lean mass by 7.4 percent.
Did the combination preserve strength? Investigators reported improved physical function alongside preserved lean mass, but whether that advantage persists over years has not been established.
What were the side effects? Muscle spasms and acne with bimagrumab, gastrointestinal symptoms and fatigue with semaglutide, and temporary increases in LDL cholesterol. No deaths were reported.
Who funded the study? Versanis Bio, which Eli Lilly acquired during the course of the trial.
What can I do about muscle loss now? Resistance training and adequate protein during weight loss have the strongest evidence. Discuss both with your clinician.
What happens next? A trial combining bimagrumab with tirzepatide is underway. Phase 3 results would be needed before any approval.
