BELIEVE shows an activin-pathway drug can protect muscle during incretin weight loss

A phase 2b trial called BELIEVE has found that adding an experimental muscle-preserving drug to semaglutide can produce large weight loss while protecting far more muscle than semaglutide alone. Results were presented June 23, 2025, at the American Diabetes Association's Scientific Sessions in Chicago ^[1][2].

The trial tested bimagrumab, a monoclonal antibody that blocks activin type II receptor signaling, a pathway that normally limits muscle growth and encourages fat storage ^[1][2]. Researchers randomly assigned 507 adults with obesity to one of nine treatment combinations, including placebo, bimagrumab alone at two doses, semaglutide alone at two doses (1 mg or 2.4 mg, the dose sold as Wegovy), and combinations of the two drugs ^[2]. Bimagrumab was given by IV infusion at weeks 4, 16, 28 and 40, while semaglutide was a once-weekly injection ^[1].

At 72 weeks, the highest-dose combination — bimagrumab 30 mg/kg plus semaglutide 2.4 mg — produced 22.1% body weight loss, compared with 15.7% for semaglutide 2.4 mg alone and 10.8% for bimagrumab 30 mg/kg alone ^[2]. The key difference was in what kind of weight came off. In the combination group, 92.8% of the weight lost was fat, versus 71.8% for semaglutide alone ^[1][2]. Lean mass fell just 2.9% in the combination group compared with a 7.4% drop with semaglutide alone; bimagrumab alone actually increased lean mass by 2.5% ^[1][2].

Other measures moved in the combination group's favor too. Total body fat fell 45.7%, versus 27.8% with semaglutide alone, and visceral fat — the fat around organs linked to metabolic disease — dropped 58.2%, compared with 35.8% with semaglutide alone ^[2]. Markers of inflammation and heart-disease risk also improved: C-reactive protein fell 83.4% in the combination group, and adiponectin, a hormone tied to lower diabetes and heart disease risk, rose more than in either drug alone ^[2]. Ninety-four percent of people on the combination lost at least 30% of their fat mass, compared with 36% on semaglutide alone ^[2]. Common side effects included muscle spasms, diarrhea and acne linked to bimagrumab, and nausea, constipation and fatigue linked to semaglutide, with no serious heart-related adverse events reported ^[2].

Why it matters for patients

Studies have found that lean body mass can account for 15% to 40% of total weight lost on GLP-1 drugs ^[1]. That matters because muscle supports strength, metabolism and long-term function, especially as people age. Louis Aronne, MD, of Weill Cornell Medicine, said the goal is a treatment that is "complementary to incretins," sparing muscle loss so weight regain after stopping treatment might also be reduced, though that has not yet been proven ^[2]. Steven Heymsfield, MD, of Pennington Biomedical Research Center, the trial's lead author, said the findings show it is possible to lose a large amount of fat "while preserving, or even enhancing, lean mass" ^[1].

Bimagrumab is not an approved drug, and the version tested was given by IV infusion, a method the researchers said would not be used going forward ^[2]. It is not yet known when, or whether, this combination could reach patients, what a subcutaneous version would look like, or how it compares long-term to other approaches such as tirzepatide, sold as Mounjaro or Zepbound ^[2].

What happens next

A 32-week withdrawal period is ongoing to see whether weight loss is better maintained after stopping treatment ^[2]. Separately, a trial combining bimagrumab with tirzepatide is already underway to test efficacy and safety of that pairing ^[1][2]. No date has been given for when full results from either study might be available.