A new strategy has emerged to reduce muscle loss during weight reduction with glucagon-like peptide-1 (GLP-1) class anti-obesity drugs.
Researchers at the AdventHealth Translational Research Institute (TRI) in the United States reported on the 9th in the journal Nature Medicine that when tirzepatide and apitegromab were administered together, total weight decreased by a similar amount, while loss of lean mass, including muscle, was smaller.
Tirzepatide is a GLP-1 class drug that aids weight loss by acting on hormone pathways involved in appetite and blood sugar control. The problem is that drug-induced weight loss does not shed only fat. Lean mass, including muscle, can also decrease during weight loss.
Lean mass refers to the body's components excluding body fat. Skeletal muscle accounts for a large portion of this. Skeletal muscle is closely related to basal metabolic rate maintenance, bodily function, physical capability, and overall health. For this reason, in obesity treatment, not only "how much was lost," but also "what was reduced" is considered an important evaluation criterion.
The researchers focused on apitegromab as a way to reduce lean mass loss during weight reduction. Apitegromab is designed to block the action of myostatin, a protein involved in regulating muscle mass. Myostatin acts as a brake to prevent muscles from growing excessively large. The researchers believed that inhibiting this protein's action could reduce muscle loss during weight loss and better preserve lean mass.
The team conducted a phase 2 clinical trial of apitegromab in 102 adults with overweight or obesity. For 24 weeks, participants received either tirzepatide plus apitegromab or tirzepatide plus a placebo.
As a result, the overall magnitude of weight loss was similar in both groups. However, the group receiving apitegromab had an average of 1.9 kg less lean mass loss than the placebo group. This means the lean mass preservation effect was about 54.9% higher.
The proportion of lean mass in total weight lost was 14.6% in the apitegromab group, compared with 30.2% in the placebo group. In other words, in the group that used apitegromab concurrently, even with similar weight loss, the proportion of loss in lean tissues such as muscle was lower, suggesting a higher likelihood that the reduction centered on fat.
There was no difference in safety. The proportion experiencing adverse events was 39% in the apitegromab group and 36% in the placebo group, showing no major difference between the groups.
However, the researchers added, "This experiment included a relatively small number of participants at 102, had a female proportion above 80%, and excluded people with major cardiometabolic diseases such as diabetes," and noted, "Larger studies in more diverse patients are needed going forward."
References
Nature Medicine (2026), DOI: https://doi.org/10.1038/s41591-026-04440-4