According to findings from a phase 2 trial published in Nature Medicine, a monoclonal antibody targeting myostatin reduced lean body mass loss by more than half during treatment with the GLP-1 or glucose-dependent insulinotropic polypeptide receptor agonist tirzepatide, while the overall weight loss remained unchanged.

These findings address a growing concern surrounding obesity pharmacotherapy. Weight loss typically involves a reduction in both fat mass and lean body mass, which includes muscle, bone, connective tissue, and body water. Loss of muscle mass is considered particularly important because of its potential effects on strength, physical performance, and metabolic health.

Muscle Preservation

Speaking with the Science Media Center, Haiko Schlögl, MD, endocrinologist, diabetologist, and nutrition specialist at the University Hospital Leipzig in Leipzig, Germany, noted that preserving muscle mass remains an important challenge during weight loss. He added that the issue may be especially relevant among individuals receiving incretin-based therapies because many discontinue treatment and subsequently regain weight, much of it as fat mass.

Weight Regain

Real-world data suggest that approximately half of the patients discontinue treatment within the first year.

“However, the weight regained is primarily fat mass. After discontinuing treatment, patients may eventually return to their original body weight but with less muscle mass than before,” Schlögl said.

Apitegromab inhibits the activation of myostatin, a protein that limits skeletal muscle growth.

To evaluate its effects during pharmacologic weight loss, Richard Pratley, MD, from the AdventHealth Translational Research Institute in Orlando, Florida, and colleagues enrolled 102 adults with overweight or obesity in a 24-week trial. The participants received tirzepatide in combination with either apitegromab or placebo.

Less Muscle Loss

By the end of the study, weight loss was similar in both groups, averaging 11.2 kg among participants receiving apitegromab and 12.5 kg in those receiving placebo.

However, the proportion of weight loss attributable to lean body mass, assessed by DEXA, differed substantially between the groups. Lean body mass accounted for 14.6% vs 30.2% of the total weight loss in the apitegromab group vs the placebo group.

On average, participants treated with apitegromab lost 1.9 kg less lean body mass than those receiving the placebo. According to the investigators, this corresponded to a 54.9% improvement in lean body mass. A significant difference between the groups remained evident 8 weeks after the treatment ended.

Apitegromab was generally well tolerated. Adverse events occurred in 76% of the participants receiving the antibody and 71% of those receiving the placebo.

Nausea, fatigue, and headache were reported more frequently in the apitegromab group, although most events were mild and transient and did not result in treatment discontinuation.

Need for Larger Studies

The authors concluded that selective myostatin inhibition with apitegromab may help preserve lean body mass during tirzepatide treatment. However, the authors cautioned that this study was relatively small and had several limitations.

More than 80% of the participants were female, and individuals with cardiometabolic conditions such as diabetes were excluded. As a result, these findings may not be generalizable to a broader patient population.

Schlögl described apitegromab as “it could become a valuable treatment option for individuals who are unable to combine tirzepatide therapy with the recommended exercise and nutrition program.”

However, he emphasized that larger, longer-term studies are needed to establish the safety and effectiveness of this therapy, particularly in individuals with diabetes and cardiovascular disease.

This story was translated from Medscape’s German edition.