In 2004, a baby was born in Germany who was, by any normal measure, impossible. He was a few days old, and he already had visible muscles — his thighs and upper arms looked like a tiny bodybuilder. Doctors checked him for every disease that could explain it, and found nothing wrong. He wasn't sick. He was just extraordinarily, effortlessly strong. [1]
When researchers looked at his genes, they found the answer. He had been born with both copies of a single gene switched off — a gene that makes a protein called myostatin. And myostatin, it turns out, has one job in the body: to put the brakes on muscle growth. It is one of the reasons muscle growth does not continue indefinitely. This baby's brakes were simply gone. [1]
Scientists had found the myostatin gene just seven years earlier, in 1997. And the moment they understood what it did, the implications were staggering. If myostatin could be switched off in anyone, on purpose, it might be possible to beat the diseases that waste muscle away — like muscular dystrophy — and even sarcopenia.
There was just one problem. For nearly thirty years, nobody could switch the myostatin gene off safely. But the breakthrough — which has just been published — arrived in time to address a growing problem that did not even exist in 1997.
Table of Contents
- The problem that didn't exist in 1997
- The thirty-year quest to switch off myostatin
- The two drugs out in front
- EMBRAZE: putting the clean drug to the test
- What actually works right now
- References
The problem that didn't exist in 1997
That problem was an unintended consequence of what has happened to weight loss in just the last few years. Medicine has become astonishingly good at reducing fat. A decade ago, the best drugs took about eight percent off body weight, and with the burden of daily injections, most people gave up. [2][3]
Then came semaglutide — Ozempic — and that increased weight loss to around fifteen percent. [4] Then tirzepatide pushed past twenty percent. [5] And the newest one in line, a triple-target drug called retatrutide, took participants down by about twenty-eight percent of their body weight in its big trial. For someone starting at a hundred and ten kilos, that is more than thirty kilos gone from a weekly injection — bariatric-surgery territory, without the surgery. [6]
But here is the catch that has been all over the internet. When that much weight is lost, some of what goes is not fat — it's muscle. People started to panic that GLP-1 drugs were melting muscle away.
The truth, however, is more boring and more reassuring than the panic. When researchers pooled twenty-two trials of these drugs and measured exactly where the lost weight came from, about a quarter was muscle and three quarters was fat. [7]
And here is what most people miss: that 25% lean mass loss is not unique to Ozempic. A quarter is roughly what people lose when dieting the old-fashioned way. It is roughly what is lost after weight-loss surgery. Researchers have documented for decades that about a quarter of any weight lost is lean tissue. [8] These drugs are not doing something sinister — they are doing what weight loss has always done.
And when one group went further and measured muscle directly with MRI scans — comparing people on tirzepatide against thousands who lost weight naturally — the muscle loss was, for the same amount of weight, basically identical. And the fat marbled inside the muscle, the kind that makes older muscle weak, actually went down. [9]
Muscle loss can be countered somewhat with good protein intake and resistance exercise. The current evidence suggests that adequate dietary protein — roughly 1.2 to 1.6 grams per kilogram of body weight per day — and regular resistance training are the most effective tools available to people on GLP-1 drugs today. But even with those in place, some muscle loss remains. The ideal outcome — losing only fat, not lean mass — brings the science back to myostatin.
The thirty-year quest to switch off myostatin
In 1997, researchers bred mice with the myostatin gene deleted — and the mice grew enormous. They looked exactly like the "double-muscled" cattle farmers had bred for centuries — bulging, blocky, with twice the muscle of a normal animal, from a single switch turned off. [10][11]
The implication was obvious. If turning the myostatin gene off doubles muscle in a mouse, a drug that turns it off in a person could rebuild the wasted muscle of dystrophy or old age. Then in 2004 came the proof it might be safe in humans — that German baby, walking around extraordinarily strong and completely healthy. Turn this gene off, it seemed, and nothing breaks. [1]
So the target was obvious, safety looked reassuring, and the prize was enormous. And then, for nearly thirty years, almost everyone who tried to hit it failed. The tool of choice is a monoclonal antibody — a guided missile designed to lock onto one specific molecular shape and neutralise it. The problem is that myostatin, once it is active, looks almost identical to a whole family of related proteins the body needs for other jobs. A missile aimed at active myostatin tends to hit its cousins too — causing side effects, or blunting pathways that were never intended to be touched. Decades of attempts, and the verdict in the field became almost a punchline: great expectations, limited success. [12]
The breakthrough, when it came, was about precision — about selectivity. The newest drug, apitegromab, does not go after active myostatin, where all the look-alike cousins are. It grabs myostatin earlier — in its inactive, folded-up precursor form, before it is ever switched on. And that precursor shape is unique. Nothing else in the family looks like it. So the missile finally locks onto myostatin and only myostatin, leaving everything else alone. That selectivity — hitting one target cleanly — is exactly what thirty years of attempts had been missing. [13]
And before anyone pointed this drug at weight loss, it earned its stripes somewhere far more demanding. Apitegromab was first tested in spinal muscular atrophy — a brutal genetic disease that destroys the muscle of children. In trials, it improved motor function in kids who were losing it, and did so safely. [14] The tool had finally matured — a clean, selective, human-proven way to take the brake off muscle formation. And it matured at the exact moment the new weight-loss drugs were driving faster fat loss — and faster muscle loss — than medicine had ever seen.
The two drugs out in front
Two medications now lead the race to apply this breakthrough to the problem of muscle loss during weight loss. They represent two completely different philosophies about how aggressive the approach should be.
The first is apitegromab — the clean one. It does exactly what was described above: it selectively blocks myostatin, the brake, so the body holds on to more muscle while losing fat. It spares muscle.
But bimagrumab is the showstopper. Instead of just blocking myostatin, it blocks a broader docking port — the activin receptor — which is a much heavier hand on the whole system. On its own, it does something no diet drug does: people's muscle actually grew as their fat fell, though total weight loss was modest. Combined with semaglutide, the headline number appeared: substantial weight loss, about 92% of it from fat, with muscle largely protected. It is, genuinely, the closest thing anyone has made to "lean and ripped from a vial." [15]
But that power comes with a serious downside. Most people on bimagrumab experienced muscle spasms. About a third developed acne. And more seriously, it pushed LDL cholesterol — the kind associated with arterial disease — up by as much as nearly 17 percent. That is the wrong direction for cardiovascular health. [15] And then, quietly, in September 2025, the company developing one of the major bimagrumab combinations paused that programme. [16]
All of this creates a lingering concern: the harder a drug pushes to actually build muscle, the louder the cardiovascular safety question becomes. Push gently, and muscle is spared cleanly. Push hard enough to grow it, and cholesterol starts heading the wrong way. This is exactly why the gentle, clean drug — apitegromab — matters so much. The whole bet is that muscle can be protected without affecting the heart. So does it work?
EMBRAZE: putting the clean drug to the test
The EMBRAZE trial is the study that inspired this article. The design is beautifully simple: a hundred and two adults with obesity were all placed on tirzepatide, then split into two groups. One half also received apitegromab, the muscle-protector. The other half received a dummy infusion. Neither the patients nor the doctors knew who received which. The only difference between the two groups was that one molecule — anything that showed up in the results had to be the apitegromab doing it. After six months, everyone was scanned and the measurements were precise: how much of the lost weight was fat, and how much was muscle. [13]
And it worked. The group on apitegromab lost about half as much muscle. Both groups lost the same total weight — but in the apitegromab group, a far bigger share of that weight was fat: about eighty-five percent, versus seventy percent in the placebo group. After thirty years of failure, the brake had finally been let off safely, in adults losing weight. For the first time, researchers have shown that the ancient rule — lose weight, lose muscle — is not inevitable. It is a hugely significant achievement. [13]
But clarity about what the study did and did not find matters here, because there is a key result the headlines skipped. The apitegromab group was not measurably stronger. The trial tested this directly, using grip strength and how easily participants could stand up from a chair. On both measures, the muscle-protected group was no better than the dummy-infusion group. [13]
The drug kept muscle on the scan. But that extra muscle did not allow people to do anything more with their bodies — and those are two different things. Keeping muscle that shows up on a scan is the means. Being stronger, more capable, less frail — that is the actual goal. Only the first was proven here. There is even a fair question about whether the spared "lean mass" on the scan is fully working muscle at all — the scan cannot tell you that. [13]
Still, this trial represents where the future may be headed: a future where it is possible to reach a healthy weight while keeping strong muscles. The distinction between "preserved muscle on a scan" and "genuinely functional strength" will be the central question for the next round of trials — and it is a question worth watching closely.
What actually works right now
A brief, blunt word on what the internet will try to sell people searching "how to keep muscle on Ozempic." That search leads into a world of grey-market SARMs and muscle peptides with names like YK-11. For protecting muscle during weight loss, these have essentially no proper human evidence — no well-designed, well-conducted randomised controlled trials. What they have instead is a real track record of liver damage and worse. Not worth the money, and not worth the risk. [17]
The approach that works right now — with no prescription and no risk — is the unglamorous one: resistance training a couple of times a week, and enough protein. That is the part anyone can control, and the evidence supporting it is solid. Two sessions of resistance exercise per week, combined with protein targets above the standard recommended intake, consistently attenuate lean mass losses during caloric restriction across multiple study designs. It is not glamorous, but it has the evidence base that the grey-market alternatives simply do not.
Beyond protein and resistance training, creatine is the one supplement with the most rigorous evidence behind it for supporting muscle and strength — consistently the most studied ingredient in this space, with decades of well-controlled human trials. [18]
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References
1. https://www.nejm.org/doi/full/10.1056/NEJMoa040933
2. https://www.nejm.org/doi/full/10.1056/NEJMoa1411892
3. https://pmc.ncbi.nlm.nih.gov/articles/PMC7448157/
4. https://www.nejm.org/doi/full/10.1056/NEJMoa2032183
5. https://www.nejm.org/doi/full/10.1056/NEJMoa2206038
7. https://www.metabolismjournal.com/article/S0026-0495(24)00341-X/abstract
8. https://onlinelibrary.wiley.com/doi/10.1111/obr.12143
9. https://www.thelancet.com/journals/landia/article/PIIS2213-8587(25)00027-0/fulltext
10. https://www.nature.com/articles/387083a0
11. https://pubmed.ncbi.nlm.nih.gov/9356471/
12. https://www.mdpi.com/2073-4409/10/3/533
13. https://doi.org/10.1038/s41591-026-04440-4
14. https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(25)00225-X/fulltext
15. https://doi.org/10.1038/s41591-026-04204-0
16. https://www.biopharmadive.com/news/lilly-terminate-obesity-trial-bimagrumab-muscle-diabetes/761105/
18. https://jissn.biomedcentral.com/articles/10.1186/s12970-017-0173-z
