News · Heart & Metabolic
New drug kept muscle on while weight-loss jabs stripped it
A Nature Medicine trial of 102 adults found adding the antibody apitegromab to tirzepatide cut lean-mass loss by 1.9 kilograms over 24 weeks, without slowing total weight loss.
Based on a peer-reviewed phase 2 trial in Nature Medicine
- The phase 2 EMBRAZE trial randomized 102 adults with overweight or obesity to tirzepatide plus apitegromab or tirzepatide plus placebo, published in Nature Medicine.
- Apitegromab is an investigational monoclonal antibody that blocks activation of myostatin, a natural brake on muscle growth.
- At week 24 the apitegromab group lost 1.9 kilograms less lean mass than placebo, a 54.9% retention of lean mass, despite similar total body weight loss between groups.
- Put another way, the makeup of the weight lost shifted: about 85% fat and 15% lean tissue with apitegromab, against 70% fat and 30% lean on tirzepatide alone.
- Side effects were broadly similar: 76% of the apitegromab group and 71% of the placebo group had an adverse event, with one serious event in each arm.
- This is a 102-person, 24-week proof-of-concept study. It measured lean mass, not strength or physical function, and apitegromab is not approved for weight management.
The complaint arrived almost as fast as the prescriptions. People losing weight on drugs like tirzepatide were losing muscle along with the fat, and no one had a way to stop it. A trial published in the journal Nature Medicine has now tested one.
Researchers running a phase 2 trial gave 102 adults with overweight or obesity either tirzepatide plus an experimental antibody called apitegromab, or tirzepatide plus a placebo. After 24 weeks, apitegromab resulted in less lean mass loss than placebo, despite similar total body weight loss between groups.
What is new
Until now the muscle problem had been described rather than solved. Loss of lean mass in proportion to total weight loss is observed with incretin mimetic therapies such as tirzepatide and has the potential to adversely affect health and function. Clinicians could advise protein and weights; they had no drug that split the two kinds of tissue apart.
This is a proof-of-concept that they can be separated. The weight still came off; less of it was muscle.
What apitegromab is
The antibody targets myostatin, a protein the body makes to limit how much muscle it builds. Apitegromab selectively inhibits myostatin activation and is thereby capable of increasing muscle mass. Release the brake, and muscle is more inclined to stay.
The drug is investigational, meaning it is still in testing and not approved for treating obesity. It was originally developed for a different purpose, in a rare neuromuscular disease.
The numbers, and what they mean
The researchers describe the result as a 54.9% retention of lean mass relative to placebo. Rather more than half the muscle that would otherwise have disappeared was still there at week 24.
The more intuitive way to see it is in the composition of the loss. Higher quality of weight loss was observed for patients receiving apitegromab with tirzepatide, at 85% fat mass and 15% lean mass, compared to tirzepatide alone at 70% fat mass and 30% lean mass. Roughly speaking, the muscle share of the loss halved.
Safety looked unremarkable. Incidence of adverse events was generally similar across apitegromab-treated participants and placebo-treated participants, and serious adverse events were balanced, with one participant affected in each arm.
The gap that matters
Here is the limit worth holding on to: the trial weighed tissue, not capability. Lean mass is a scan measurement. Strength, balance and the ability to climb stairs are what people actually lose when muscle goes, and none of those were the outcome reported here.
The study is also small and short by the standards of obesity medicine, at 102 participants over 24 weeks, and it was designed as a proof of concept rather than a definitive test. The trial was run with industry involvement, which is normal for a drug in development and still worth knowing.
The authors describe their own result carefully: selective targeting of myostatin by apitegromab was well tolerated and effective in preserving lean mass when combined with tirzepatide. Preserving lean mass is the claim. Preserving function is the hope.
For anyone on these drugs today, the practical advice has not moved: lift something heavy, eat enough protein. The difference is that the muscle question now has a pharmaceutical answer in development, and a first result suggesting the idea works.
People also ask
Do weight-loss drugs really cost you muscle?
Some lean mass goes with any substantial weight loss, including dieting and surgery. The concern with incretin drugs such as tirzepatide and semaglutide is the speed and scale of the loss. This trial's own framing is that loss of lean mass in proportion to total weight loss is observed with incretin mimetic therapies and has the potential to adversely affect health and function. That is the problem apitegromab was built to address.
How much muscle did the drug actually save?
At week 24, participants on apitegromab lost 1.9 kilograms less lean mass than those on placebo, which the researchers describe as a 54.9% retention of lean mass relative to placebo. Total body weight loss was similar between the groups, so the difference was in what kind of tissue came off rather than how much.
Does saving lean mass mean you end up stronger?
Not proven here, and this is the study's main gap. Lean mass on a body scan is not the same as strength, walking speed or day-to-day function. The trial reported tissue composition, not performance. Whether preserved lean mass translates into being measurably stronger or more capable is the question a larger trial would need to answer.
Can I get apitegromab for weight loss?
No. Apitegromab is investigational, meaning it is still in testing and not approved for weight management. This was a phase 2 proof-of-concept study in 102 people over 24 weeks, which is early-stage evidence. Anyone taking or considering a weight-loss medication should discuss muscle preservation with their own doctor rather than waiting on a drug that does not yet exist as a treatment.
What can I do about muscle loss now?
The established levers are resistance training and adequate protein while losing weight. Neither was what this trial tested, so nothing here replaces them, and the researchers were not comparing their drug against exercise. If you are on a weight-loss medication, that combination remains the evidence-backed way to protect muscle.
References
- Pratley RE, Denham DS, Trivedi R, et al. Apitegromab for lean mass preservation during tirzepatide-induced weight loss: a randomized, double-blind, placebo-controlled phase 2 trial. Nature Medicine (2026).
- National Institute of Diabetes and Digestive and Kidney Diseases. Prescription Medications to Treat Overweight and Obesity.