Weight-loss drugs have transformed the treatment of obesity in recent years. Medications such as tirzepatide can help people lose a significant amount of body weight, often far more than what can be achieved through diet and exercise alone.
These treatments have given new hope to millions of people struggling with obesity and its related health problems.
However, there is an important concern that scientists and doctors have been paying increasing attention to. When people lose weight, they do not lose only body fat. Some of the weight loss also comes from lean body mass, which includes skeletal muscle.
Muscle plays a critical role in strength, mobility, balance, metabolism, and overall health. Losing too much muscle can reduce physical function and may make it harder to maintain weight loss over the long term.
A new clinical trial suggests that a drug called apitegromab may help solve this problem. Researchers found that people taking apitegromab alongside tirzepatide were able to preserve substantially more muscle mass while achieving similar overall weight loss.
The study was published in Nature Medicine and offers a potential new strategy for improving the quality of weight loss rather than simply focusing on the number shown on the scale.
To understand the importance of the findings, it helps to understand how modern weight-loss medications work. Tirzepatide belongs to a group of medicines that affect hormones involved in appetite regulation and blood sugar control. These drugs help people feel full sooner, reduce food intake, and support substantial weight loss.
While effective, studies have shown that some of the weight lost during treatment comes from lean tissue. Researchers estimate that muscle and other lean tissues can account for a meaningful portion of total weight loss. This has raised concerns, especially for older adults who may already be at risk of age-related muscle loss.
The new study focused on myostatin, a naturally occurring protein that limits muscle growth. Myostatin acts as a biological brake that prevents muscles from becoming excessively large. Scientists have long been interested in blocking myostatin because doing so may help preserve or increase muscle mass.
Apitegromab is a drug specifically designed to block myostatin activity. By reducing myostatin’s effects, researchers hoped they could help people maintain muscle while losing body fat.
The phase 2 clinical trial was led by Richard Pratley and colleagues. It included 102 adults who were overweight or obese. Participants were randomly assigned to receive either tirzepatide plus apitegromab or tirzepatide plus a placebo. Neither the participants nor the researchers knew which treatment each person received until the study was completed.
The trial lasted 24 weeks, allowing researchers to compare changes in body weight and body composition between the two groups.
At the end of the study, overall weight loss was very similar in both groups. This finding is important because it shows that preserving muscle did not interfere with the ability to lose weight.
The major difference was in what type of weight was lost.
Participants receiving apitegromab lost about 1.9 kilograms, or 4.2 pounds, less lean body mass than those receiving the placebo. This represented approximately 54.9% greater preservation of lean mass.
When researchers looked at the composition of weight loss, the differences became even clearer. In the apitegromab group, lean mass accounted for only 14.6% of total weight loss. In contrast, lean mass accounted for 30.2% of weight loss in the placebo group.
This means that people taking apitegromab lost a greater proportion of body fat while retaining more muscle tissue.
The safety results were also encouraging. Side effects occurred at similar rates in both groups. About 39% of participants receiving apitegromab experienced at least one adverse event, compared with 36% in the placebo group. Overall, the treatment appeared to be generally well tolerated.
The findings may be particularly important because muscle preservation has become one of the major challenges in obesity treatment. Maintaining muscle is important not only for physical strength but also for metabolic health. Muscle helps regulate blood sugar, supports physical activity, and contributes to long-term health and independence.
As people age, muscle loss becomes increasingly common. Therefore, treatments that help preserve muscle during weight loss could be especially valuable for older adults, although this specific study did not focus on elderly populations.
In reviewing the findings, the results are promising but should be interpreted carefully. The study was relatively small, involving only 102 participants, and more than 80% of the participants were women.
In addition, people with diabetes and significant cardiometabolic conditions were excluded, which means the findings may not apply to all patients who use tirzepatide. The study also lasted only 24 weeks, so longer-term effects remain unknown.
Nevertheless, the trial provides strong early evidence that targeting myostatin may improve the quality of weight loss by preserving muscle while reducing fat. Larger and longer studies will be needed to confirm whether this approach can improve strength, physical function, and long-term health outcomes.
If future research confirms these benefits, apitegromab could become an important companion therapy for people using modern weight-loss medications.
The study was published in Nature Medicine.
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Source: Nature Medicine study.
