The rise of powerful weight-loss medications has changed the way obesity is treated. Drugs such as tirzepatide can help people lose large amounts of weight, often producing results that were difficult to achieve with traditional approaches alone.
These medications are helping many individuals reduce their risk of obesity-related conditions and improve their quality of life.
Yet weight loss is not always as simple as losing unwanted fat. When the body sheds pounds, some of that loss often comes from muscle tissue. While losing excess fat is generally beneficial, losing muscle can be problematic because muscle is essential for strength, movement, balance, and healthy metabolism.
Researchers have therefore been searching for ways to help people lose fat while keeping as much muscle as possible. A new study published in Nature Medicine suggests that a drug called apitegromab may help achieve that goal.
The research examined whether apitegromab could help preserve lean body mass in people taking tirzepatide. Lean body mass includes skeletal muscle as well as other non-fat tissues, but skeletal muscle makes up the largest portion.
Muscle is much more than something that helps people move. It plays an important role in controlling blood sugar, supporting physical performance, maintaining independence, and protecting health as people age. People with higher muscle mass often recover better from illness and injury and may have a lower risk of physical disability later in life.
Because of these benefits, scientists are increasingly interested in the composition of weight loss. They want to know not only how much weight people lose but also whether that weight comes mainly from fat or from muscle.
Apitegromab works by targeting a protein called myostatin. Myostatin acts as a natural regulator of muscle growth. Its job is to prevent muscles from growing too large. Scientists discovered years ago that animals lacking myostatin develop unusually large muscles, which sparked interest in developing therapies that block its activity.
The idea behind apitegromab is straightforward. By blocking myostatin, the drug may help the body hold on to muscle tissue even while weight is being lost.
To test this idea, researchers conducted a randomized, double-blind, placebo-controlled phase 2 clinical trial. These types of studies are considered among the most reliable methods for evaluating potential treatments because they reduce bias and allow fair comparisons between groups.
The trial enrolled 102 adults with overweight or obesity. Participants received either tirzepatide plus apitegromab or tirzepatide plus a placebo for 24 weeks.
Both groups lost similar amounts of total body weight. This showed that apitegromab did not reduce the effectiveness of tirzepatide as a weight-loss treatment.
The difference emerged when researchers analyzed body composition.
People receiving apitegromab retained substantially more lean body mass. Compared with the placebo group, they lost 1.9 kilograms less lean mass. This translated into nearly 55% greater preservation of lean tissue.
The researchers also calculated how much of each participant’s weight loss came from lean mass. In the placebo group, nearly one-third of total weight loss came from lean tissue. In contrast, only about 15% of weight loss in the apitegromab group came from lean tissue.
This means that a larger proportion of weight loss came from fat rather than muscle.
Safety is always an important consideration with new therapies. Fortunately, the study found that side effects were generally similar between the two groups. Approximately 39% of people receiving apitegromab reported at least one adverse event, compared with 36% in the placebo group.
The findings may have important implications for future obesity treatment. Preserving muscle during weight loss could potentially improve physical function, maintain strength, and support long-term metabolic health.
This issue may become increasingly important as more people use powerful weight-loss medications. Some experts worry that excessive muscle loss could reduce some of the long-term benefits of weight reduction, particularly among older adults who already experience age-related declines in muscle mass.
At the same time, important questions remain unanswered. Researchers do not yet know whether preserving more muscle will translate into measurable improvements in strength, mobility, exercise performance, or long-term health outcomes. Those questions will require larger and longer studies.
In reviewing the study, the findings provide an encouraging proof of concept that muscle-preserving therapies can be combined with modern weight-loss medications. The study was carefully designed and demonstrated a clear effect on body composition. However, the trial included a relatively small number of participants, most of whom were women.
People with diabetes and significant cardiometabolic diseases were excluded, limiting the ability to generalize the findings to broader patient populations. Additional studies involving more diverse participants and longer follow-up periods will be necessary.
Even so, the results suggest that future obesity treatments may focus not only on how much weight people lose but also on preserving strength and muscle mass during the process. This shift could help make weight loss healthier and more sustainable over the long term.
The study was published in Nature Medicine.
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Source: Nature Medicine study.
