A new study presented at the 2025 American Diabetes Association Scientific Sessions found that combining semaglutide with bimagrumab could reduce fat mass while preserving or increasing lean muscle in adult patients with overweight or obesity.
In the double-blind, placebo-controlled, multicenter phase IIb clinical trial, researchers randomly assigned 507 adult patients to receive semaglutide alone, bimagrumab alone, or both drugs in combination. Semaglutide was administered weekly via subcutaneous injection, while bimagrumab was given through intravenous infusion at weeks 4, 16, 28, and 40.
The primary outcome of the trial was the change in total body weight. Secondary measures included changes in body fat, visceral adipose tissue, waist circumference, inflammation markers, and lean body mass.
The participants receiving combination therapy lost an average of 22.1% of their body weight, with 92.8% of that loss attributed to fat mass. In comparison, semaglutide alone led to a 15.7% reduction, with 71.8% of the loss from fat mass. Bimagrumab alone resulted in a 10.8% weight reduction, all of which was from fat mass. Notably, bimagrumab monotherapy also produced a 2.5% increase in lean mass.
The researchers addressed concerns that current glucagon-like peptide (GLP)-1–based therapies may lead to muscle loss. Previous data suggested that 15% to 40% of the weight lost with these medications may come from lean tissue, including muscle. With the use of incretin-based therapies increasing by nearly 600% over the last 5 years in the United States, muscle preservation during weight loss is becoming an important consideration in obesity treatment.
Semaglutide is a GLP-1 receptor agonist that promotes weight loss and glycemic control. Bimagrumab is a monoclonal antibody that blocks activin type II receptors to support muscle growth and prevent breakdown. The researchers designed the trial to evaluate whether combining these mechanisms could produce higher-quality weight loss by maximizing fat reduction while minimizing muscle loss.
In a separate presentation at the 2025 American Diabetes Association (ADA) Scientific Sessions, researchers introduced a biosensor prototype that may help clinicians monitor muscle breakdown in real time. The DNA-based aptamer sensor detects phenylalanine, an amino acid released during muscle catabolism or following protein ingestion. Laboratory tests showed that the sensor could detect phenylalanine across a wide range of concentrations, with a detection limit of 4 µM/L and stable performance over 7 days.
The biosensor aimed to provide a tool for tracking lean mass changes in patients using GLP-1–based medications, older adults, or those at risk of sarcopenia. The researchers plan to conduct clinical trials to evaluate its use in real-world settings.
Further studies are underway to test bimagrumab in combination with tirzepatide to explore additional safety and efficacy outcomes.
Both studies highlighted emerging approaches to improving weight loss quality—emphasizing fat reduction while preserving muscle mass.
Source: 2025 ADA Scientific Sessions
Late-Breaking Symposia Presentation. Can we improve the quality of weight loss by augmenting fat mass loss while preserving lean mass? The BELIEVE study of bimagrumab + semaglutide
Late-Breaking Poster Presentation. Continuous protein sensor for sarcopenia management during GLP-1 RA therapy
