Muscle is harder to rebuild once lost
As millions turn to GLP-1 medications like Ozempic and Mounjaro to reshape their bodies, science is confronting an unintended consequence: the quiet erosion of muscle alongside fat. A new drug, apitegromab, has shown early promise in preserving lean tissue during weight loss, raising the possibility that the body need not pay so steep a price for transformation. The finding invites a deeper question about what it means to lose weight well — not merely less of oneself, but less of the wrong parts.
- GLP-1 drugs like Ozempic are triggering widespread muscle loss, with up to a third of shed weight coming from lean tissue rather than fat — a side effect now visible enough to have earned its own nickname.
- Plastic surgeons are fielding a surge of consultations from patients left with sagging, deflated contours after rapid weight loss, signaling that the cosmetic and physical toll is already being felt.
- A six-month clinical trial found that apitegromab preserved 1.9kg more muscle mass in Mounjaro users — cutting muscle's share of total weight loss nearly in half — without blunting fat loss.
- The drug works by blocking a protein that triggers muscle breakdown, essentially instructing the body to protect what it has built even as calories run scarce.
- Experts are tempering enthusiasm: the trial was short, the sample small, and whether preserved muscle translates to real-world strength or longevity remains unproven.
- Apitegromab is not yet available outside trials and requires intravenous delivery — though a self-injecting pen format is being explored, which could eventually bring it closer to everyday use.
When people take Ozempic, Wegovy, or Mounjaro to lose weight, the body doesn't just shed fat — it sheds muscle too. Research suggests roughly one-third of weight lost on these GLP-1 medications comes from lean tissue rather than fat stores. The result is a phenomenon users have begun calling 'Ozempic butt': a flattening and sagging of the body as both fat and the muscle that gives it shape disappear together. Plastic surgeons across America report a noticeable rise in consultations from people seeking to reverse the effect.
The mechanism is familiar. These drugs reduce appetite and extend fullness, so people eat less and lose weight quickly. But a calorie-starved body doesn't discriminate neatly between fat and muscle — and muscle, unlike fat, is slow and difficult to rebuild. The rapid pace of loss these medications enable can outstrip the body's ability to protect itself.
A new drug called apitegromab may offer a partial answer. In a six-month study of 102 adults using Mounjaro, those who also received apitegromab preserved roughly 1.9 kilograms more muscle mass than those on placebo — about 55 percent more lean tissue — without any reduction in fat loss. In the placebo group, muscle accounted for 30 percent of total weight lost; in the apitegromab group, that figure fell to under 15 percent. The drug works by blocking a protein involved in muscle breakdown, signaling the body to hold on to what it has.
Experts are cautious. Researchers not involved in the study describe the results as encouraging but preliminary, noting that a six-month trial cannot confirm whether preserved muscle translates to better strength, quality of life, or long-term health. Some suggest the drug may be most useful for those experiencing unusually rapid muscle loss, rather than all GLP-1 users.
Apitegromab remains unavailable outside clinical trials and currently requires intravenous administration — a meaningful barrier. Its developers are exploring a self-injecting pen format that could eventually make it more accessible. Until then, the guidance for people on GLP-1 medications remains unchanged: prioritize protein, exercise regularly, and lean on strength training. Apitegromab, for now, is a horizon rather than a remedy.
When people take Ozempic, Wegovy, or Mounjaro to lose weight, something unexpected often happens alongside the shrinking numbers on the scale. The body doesn't just shed fat. It sheds muscle too—sometimes a lot of it. Research from the United States suggests that roughly one-third of the weight lost on these GLP-1 medications comes not from fat stores but from lean muscle tissue. The result is a phenomenon users have begun calling "Ozempic butt": a flattening and sagging of the buttocks and other areas as the body loses both fat and the muscle that gives it shape and firmness. Plastic surgeons across America report a noticeable uptick in consultations from people seeking to reverse this effect.
The mechanism is straightforward enough. These injectable medications work by reducing appetite and extending the feeling of fullness, so people eat less and lose weight faster. But the body, when starved of calories, doesn't discriminate evenly between fat and muscle. Muscle is harder to rebuild once lost. Unlike fat, which the body can relatively quickly mobilize and burn, muscle requires sustained effort—strength training, adequate protein—to recover. The rapid weight loss these drugs enable can outpace the body's ability to preserve what it needs.
Now a new medication called apitegromab offers a potential solution. In a six-month study involving 102 adults, mostly women, researchers tested whether apitegromab could protect muscle while people lost weight on Mounjaro, one of the most popular GLP-1 drugs. The results were encouraging. Participants who received apitegromab alongside their obesity treatment preserved roughly 1.9 kilograms more muscle mass than those on placebo—about 55 percent more lean tissue. Critically, this muscle preservation did not come at the cost of fat loss. The drug works by blocking a protein involved in muscle breakdown, essentially telling the body to hold onto what it has built.
In the placebo group using only Mounjaro, lean muscle accounted for 30.2 percent of total weight loss. In the apitegromab group, that figure dropped to 14.6 percent—meaning far more of the weight shed came from fat rather than muscle. The difference is not trivial. It is the difference between emerging from weight loss looking depleted and emerging looking proportional.
Yet experts urge caution. Marie Spreckley, a researcher not involved in the study, calls the results "initial encouraging evidence" rather than proof of lasting clinical benefit. She and others point out that a six-month trial, while promising, does not tell us whether preserving muscle mass actually translates to better strength, improved quality of life, or better health outcomes over years. Brendan Gabriel, a specialist in health and nutrition at the University of Aberdeen, suggests the drug may not be right for everyone taking GLP-1 medications, but could help those experiencing particularly rapid muscle loss.
Apitegromab is not yet available outside clinical trials. It must currently be administered intravenously, a significant limitation. The company developing it is exploring whether the drug could eventually be delivered via a self-injecting pen, similar to the devices people already use for Ozempic and its cousins. If that becomes possible, the path to wider use would be clearer.
In the meantime, people taking GLP-1 medications are advised to do what they have always been told to do: eat well, prioritize protein—roughly 20 to 40 grams per meal—and exercise regularly, especially strength training. These basics remain the most reliable defense against muscle loss. The hope is that apitegromab, if it proves safe and effective in larger, longer studies, could one day serve as a backup plan for those who struggle to preserve muscle through diet and exercise alone. For now, it remains a possibility on the horizon rather than a solution in hand.
Notable Quotes
Initial encouraging evidence, not proof of lasting clinical benefit— Marie Spreckley, researcher
The treatment may not be appropriate for all GLP-1 users, but could benefit those with accelerated muscle loss— Brendan Gabriel, University of Aberdeen
The Hearth Conversation Another angle on the story
So the problem is that when people lose weight on these drugs, they're losing muscle along with the fat. Why does that happen?
The drugs work by making you feel full, so you eat less. Your body then needs energy, and it burns both fat and muscle. But muscle is harder to rebuild—it needs strength training and protein. Fat is easier for the body to mobilize and use up quickly.
And this "Ozempic butt" thing—that's just what it looks like when muscle disappears?
Exactly. The buttocks and other areas lose both fat and the muscle underneath that gives them shape and firmness. It's not a medical diagnosis, just what people are calling the visible effect. Plastic surgeons are seeing more consultations about it.
This new drug, apitegromab—how does it actually work?
It blocks a protein that breaks down muscle. So while you're losing weight and burning fat, the drug is essentially telling your muscles to stay put. In the study, people on apitegromab kept about 1.9 kilograms more muscle than those on placebo.
That sounds significant. So is this the answer?
Not yet. The study was only six months long, and experts want to see longer trials. They want to know if keeping that muscle actually makes people stronger and healthier in the long run, not just whether the numbers look better on a scan.
What about people who can't wait for more studies?
Right now, the standard advice is still the best: eat enough protein, do strength training, and don't expect these drugs to be a quick fix. Apitegromab might eventually help, but it's still in trials and has to be given intravenously. They're working on a pen version.