85 percent of weight lost was fat, versus 70 percent in the placebo group
As modern medicine grows more capable of shrinking the body, it confronts an older question: what kind of body are we trying to preserve? A small but carefully designed trial suggests that blocking a single protein—myostatin—may allow people using tirzepatide to lose weight predominantly as fat rather than muscle, nudging the outcome of obesity treatment closer to what patients and clinicians have long hoped for. The EMBRAZE trial, enrolling 102 participants across multiple centers in 2024, offers early evidence that the composition of weight loss, not just its quantity, can be deliberately shaped.
- Modern GLP-1 weight-loss drugs like tirzepatide are effective, but they extract a hidden cost: a meaningful share of the weight lost comes from muscle, not fat.
- The EMBRAZE trial tested whether apitegromab—an antibody that blocks myostatin, the body's muscle-breakdown signal—could protect lean tissue without undermining fat loss.
- After 24 weeks, apitegromab users lost 85% of their weight as fat compared to 70% in the placebo group, retaining nearly 2 kilograms more lean mass with no reduction in total weight lost.
- The effect persisted eight weeks after stopping both drugs, and the antibody was well tolerated, with serious adverse events in only about 2% of each group.
- Researchers are cautious: this was a proof-of-concept phase 2 study with a small sample, and no significant improvements in strength, mobility, or heart health were detected yet.
- Larger, longer trials in people with diabetes and cardiovascular disease are now needed before apitegromab can be considered a genuine companion to weight-loss therapy.
When people lose weight on tirzepatide, not all of what disappears is fat. A meaningful portion is lean tissue—the muscle that sustains strength, mobility, and metabolic health. A new trial suggests this may not be inevitable.
The EMBRAZE trial enrolled 102 people with overweight or obesity between June and September 2024. Half received apitegromab, an experimental myostatin-blocking antibody, alongside tirzepatide; the other half received tirzepatide with a placebo. Participants were mostly women in their early 40s, weighing roughly 93 to 99 kilograms at enrollment, all of whom had been unable to lose weight through diet alone.
Apitegromab works by intercepting myostatin's precursors before they become active, effectively placing a brake on muscle breakdown during weight loss. After 24 weeks, both groups had lost comparable amounts of total weight—but the composition diverged sharply. In the apitegromab group, 85 percent of weight lost came from fat; in the placebo group, only 70 percent did. The antibody group retained nearly 2 kilograms more lean mass, an effect that held up eight weeks after both drugs were stopped.
The drug was well tolerated, with serious adverse events in roughly 2 percent of each group and none attributed to apitegromab. Blood markers confirmed the drug was engaging its intended biological target.
Still, the researchers were measured in their conclusions. This was a phase 2 proof-of-concept study—small, using wider confidence intervals than standard practice, and unable to detect meaningful differences in physical function or cardiometabolic outcomes. Whether preserving lean mass translates to better strength or heart health remains an open question.
What follows will be larger trials in more diverse populations, with longer follow-up and more precise measurement tools. If those studies confirm this signal, apitegromab could become a companion to tirzepatide and similar drugs—helping people not just lose weight, but lose it in a way that leaves them functionally stronger.
When people take tirzepatide to lose weight, their bodies shed pounds in a particular way: some fat goes, but so does muscle. After six months on the drug, a person might weigh 10 kilograms less, but a troubling portion of that loss comes from lean tissue—the muscle that keeps them strong, mobile, and metabolically healthy. A new trial suggests there may be a way to change that equation.
Researchers at multiple centers enrolled 102 people with overweight or obesity between June and September 2024 in what they called the EMBRAZE trial. Half received apitegromab, an experimental antibody, alongside tirzepatide; the other half received placebo with the same tirzepatide dose. The participants were mostly women in their early 40s, weighing between 93 and 99 kilograms at the start. All had tried to lose weight through diet alone without success in the three months before the study began.
Apitegromab works by blocking myostatin, a protein that tells the body to break down muscle. By binding to myostatin's precursors before they become active, the antibody essentially puts a brake on muscle loss during weight reduction. The question was whether this brake would actually work in humans taking tirzepatide, and whether it would slow down fat loss in the process.
After 24 weeks, the answer was clearer than researchers might have dared hope. Both groups lost similar amounts of total weight. But the composition of that loss diverged sharply. In the apitegromab group, 85 percent of the weight shed came from fat—about 8.5 kilograms. In the placebo group, only 70 percent came from fat, about 8.0 kilograms. The difference meant that apitegromab recipients retained nearly 2 kilograms more lean mass than those on placebo alone. Measured another way, the antibody preserved 54.9 percent more lean mass relative to what the placebo group retained.
The findings held up eight weeks after people stopped taking the drugs, suggesting the effect was durable. Blood tests showed that apitegromab successfully engaged its biological target—myostatin levels rose and then stabilized, indicating the drug was doing what it was designed to do. The antibody was well tolerated overall. More than 70 percent of participants in both groups reported some adverse event, but serious adverse events occurred in only about 2 percent of each group, and none were attributed to apitegromab. Nausea, fatigue, and headache appeared somewhat more often in the apitegromab arm.
Yet the trial was small, and researchers were careful about their claims. This was a phase 2 study—proof of concept, not proof of clinical benefit. The team used 80 percent confidence intervals rather than the standard 95 percent, and did not adjust for multiple comparisons. The analysis was based primarily on people who completed the trial. The researchers found no significant differences between groups in physical function tests or cardiometabolic measures, which means they cannot yet say whether preserving lean mass actually translates to better strength, mobility, or heart health.
What comes next is larger trials in more diverse populations—people with diabetes, heart disease, and other obesity-related conditions. Researchers want longer follow-up periods and better ways to measure muscle, since the DEXA scans used here cannot fully distinguish muscle from other lean tissue and can be affected by hydration. If those trials confirm what this one suggests, apitegromab could become a companion drug to tirzepatide and other weight-loss medications, helping people reshape their bodies in a way that preserves the tissue they need to function.
Notable Quotes
Apitegromab recipients maintained nearly 2 kg more lean mass than placebo recipients after 24 weeks— Study findings from EMBRAZE trial
The Hearth Conversation Another angle on the story
Why does it matter that people lose muscle when they take tirzepatide? Isn't weight loss weight loss?
Because muscle is what keeps you moving. Lose too much of it and you become weaker, more prone to falls, less able to do the things you need to do. And metabolically, muscle burns calories at rest. Lose it and your metabolism slows down, making it harder to keep weight off long-term.
So this drug apitegromab—it just stops the body from breaking down muscle?
It blocks myostatin, which is a signal that tells muscle to degrade. Think of it as intercepting a message before it reaches the muscle cells. The body still loses fat because tirzepatide is doing that work. Apitegromab just protects the muscle from being collateral damage.
The trial showed people lost similar amounts of total weight. So why take apitegromab at all if the scale reads the same?
Because the scale doesn't tell you what you're made of. Two people can weigh the same but have very different body compositions. One might be mostly muscle, the other mostly fat. The person with more muscle will be stronger, healthier, and better positioned to maintain their weight long-term.
What's the catch? The trial was small, right?
Very small—102 people. And they didn't see improvements in actual physical function or heart health markers yet. This is proof the mechanism works, not proof it makes people's lives better. You need bigger, longer trials to know that.
How long before this could be available to patients?
Years, probably. They need phase 3 trials in larger, more diverse groups—people with diabetes, heart disease, the conditions that actually drive obesity treatment in the real world. And they need to figure out if preserving muscle actually translates to better outcomes. Right now it's a promising signal, not a finished story.