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For years, metabolic research has focused on one headline measurement:
How much body weight can be lost?
That question is beginning to change.
As GLP-1 and other incretin-based medicines produce increasingly substantial reductions in body weight, researchers are paying much closer attention to what that lost weight actually consists of.
Fat mass is only part of the equation.
Weight reduction can also involve loss of lean tissue, including skeletal muscle. This has created an emerging research question:
Can substantial fat loss occur while more muscle is preserved?
One of the compounds at the centre of this research is trevogrumab.
Trevogrumab is an investigational monoclonal antibody targeting myostatin, a biological regulator involved in limiting skeletal-muscle growth.
New Phase 2 results reported in October 2026 have brought the compound — and the wider concept of muscle-preserving metabolic therapy — into much greater focus.
What is trevogrumab?
Trevogrumab is an investigational anti-myostatin monoclonal antibody developed by Regeneron.
Rather than acting on GLP-1, GIP, glucagon or amylin receptors, trevogrumab targets an entirely different biological pathway.
Its target is myostatin, also known as growth differentiation factor 8 or GDF8.
Myostatin acts as a natural regulator of skeletal-muscle growth.
Blocking myostatin signalling has therefore been investigated as a potential way of preserving or increasing muscle tissue.
This is what makes trevogrumab particularly interesting in the current metabolic landscape.
Researchers aren’t primarily studying it as another compound designed to suppress appetite.
They’re investigating whether it can affect body composition.
What is myostatin?
Myostatin is a protein predominantly produced in skeletal muscle.
One of its biological roles is to restrict excessive muscle growth.
Its importance became particularly clear through rare genetic mutations affecting myostatin signalling, which can result in unusually high muscularity.
Researchers have consequently investigated myostatin inhibition in several areas involving muscle loss.
The rapid growth of incretin-based weight-loss therapy has now created another potential application.
Why can muscle loss occur during weight loss?
When body weight falls substantially, the tissue being lost isn’t necessarily exclusively fat.
Some reduction in lean mass commonly occurs alongside fat loss.
That isn’t unique to GLP-1 medicines — it can happen during weight reduction more generally.
However, the magnitude of weight loss now achievable with modern metabolic therapies has increased scientific interest in preserving skeletal muscle, particularly among people who may already be vulnerable to reduced muscle mass.
A 2026 review described muscle preservation as an emerging frontier of obesity pharmacotherapy, while stressing that the clinical significance of preserving measured lean mass still requires further investigation.
How does trevogrumab work?
Trevogrumab binds to myostatin and inhibits its activity.
This reduces signalling that normally restricts skeletal-muscle growth.
Importantly, that’s completely different from the mechanisms we’ve covered in recent Klarity Research articles.
Tirzepatide:
GIP + GLP-1
Retatrutide:
GIP + GLP-1 + glucagon
Zenagamtide:
GLP-1 + amylin
Trevogrumab:
myostatin inhibition
So rather than creating another route to greater appetite or metabolic effects, researchers are exploring whether trevogrumab can change the composition of the weight being lost.
What is the COURAGE trial?
COURAGE is a Phase 2 clinical study examining trevogrumab alongside semaglutide in adults with obesity.
The trial involved almost 1,000 participants and investigated whether inhibiting myostatin could help preserve lean tissue during semaglutide-associated weight reduction.
Updated findings were presented at the European Association for the Study of Diabetes annual meeting at the end of September and announced by Regeneron on 1 October 2026.
This makes the research particularly current.
Did trevogrumab preserve muscle?
The new results suggest an effect on muscle preservation.
In a predefined MRI substudy, Regeneron reported that trevogrumab prevented approximately 70% of the muscle loss associated with semaglutide treatment at the investigated dose.
The company also reported greater preservation among participants meeting a definition of low lean mass associated with sarcopenia.
These findings are important, but they need careful interpretation.
Preserving a measurement of muscle or lean mass doesn’t automatically demonstrate improvements in strength, mobility or physical function.
Those outcomes are becoming some of the most important unanswered questions in this field.
Is lean mass the same as muscle?
No — and this distinction matters.
Lean mass isn’t simply another term for skeletal muscle.
Body-composition measurements of lean mass can include water, organs and other non-fat tissues.
Researchers can use techniques including DXA and MRI to examine different aspects of body composition.
This is one reason the trevogrumab MRI data are particularly interesting: researchers are trying to understand changes specifically involving muscle rather than relying exclusively on overall lean-mass measurements.
Does preserving muscle mean less weight loss?
Not necessarily.
This is one of the most interesting concepts behind the research.
If somebody loses more fat while retaining more muscle, the number on the scales might theoretically be higher than if they lost both fat and muscle.
Yet their body composition could be more favourable.
This exposes a limitation of using total body weight as the only measure of success in metabolic research.
Future studies may increasingly consider:
fat mass
visceral fat
skeletal muscle
lean mass
strength
and physical function
alongside total weight.
Trevogrumab vs bimagrumab: what’s the difference?
We’ve already covered bimagrumab separately in our Klarity Research series, and the two compounds shouldn’t be confused.
Trevogrumab directly targets myostatin.
Bimagrumab targets activin type II receptors.
Both approaches interact with biological pathways involved in muscle and body composition, but at different points in the signalling system.
In the 2026 BELIEVE study, bimagrumab combined with semaglutide also produced substantial fat-mass reductions while reducing the loss of lean mass seen with semaglutide alone.
The emergence of several different approaches suggests that body composition is becoming a significant research category in its own right.
What about apitegromab?
Apitegromab provides another important comparison.
Like trevogrumab, it targets the myostatin pathway, although the precise mechanism differs.
A Phase 2 study published in Nature Medicine in June 2026 investigated apitegromab alongside tirzepatide.
At 24 weeks, participants receiving apitegromab had approximately 1.9 kg less lean-mass loss, representing around 55% relative preservation compared with the placebo combination, while overall body-weight loss was similar.
So trevogrumab isn’t an isolated experiment.
Several independent programmes are now investigating whether muscle-related pathways can complement incretin therapy.
What is garetosmab?
Garetosmab is another Regeneron antibody, but it targets activin A rather than myostatin.
COURAGE investigated combinations involving trevogrumab and garetosmab.
However, Regeneron discontinued development of the combination after safety and tolerability concerns, while continuing to investigate trevogrumab.
This is an important reminder that adding additional biological targets doesn’t automatically produce a better therapy.
Benefits have to be considered alongside safety.
Is trevogrumab a peptide?
No.
Trevogrumab is a monoclonal antibody.
That’s another reason this article broadens our recent series.
We’ve now been looking at peptides, small molecules, dual and triple agonists, amylin compounds and antibodies affecting muscle-related pathways.
Modern metabolic research is becoming far broader than peptide agonism alone.
Is trevogrumab approved?
No.
Trevogrumab remains investigational.
The COURAGE results come from Phase 2 research and do not mean that trevogrumab has been approved for obesity, muscle preservation or use alongside GLP-1 medicines.
Further clinical development is required.
Can you buy trevogrumab in the UK?
There is no authorised trevogrumab medicine available for routine use in the UK.
Products marketed online using names of experimental compounds shouldn’t be confused with regulated medicines that have completed clinical development and regulatory review.
Is muscle loss with GLP-1 drugs dangerous?
This requires a more nuanced answer than many online discussions suggest.
Some loss of lean tissue commonly accompanies substantial weight reduction.
The unresolved question is when that loss becomes clinically important.
Age, starting muscle mass, nutritional status, physical activity and other individual characteristics may all matter.
Researchers are particularly interested in people who already have low muscle mass or are at greater risk of sarcopenia.
Crucially, scientists still need to establish whether pharmacologically preserving lean mass translates into meaningful improvements in strength, mobility, independence or other health outcomes.
Can resistance training and protein help preserve muscle?
This is another increasingly common question.
Exercise and appropriate nutritional support remain fundamental areas of muscle-preservation research and clinical practice.
Pharmaceutical research into myostatin inhibitors shouldn’t be interpreted as making those factors irrelevant.
Instead, researchers are investigating whether pharmacological approaches could eventually provide an additional strategy, particularly for populations at greater risk of muscle loss.
Is “quality of weight loss” becoming more important?
Potentially, yes.
This may become one of the defining ideas of the next generation of metabolic research.
The first era largely asked:
How much weight can we reduce?
The next may increasingly ask:
Where did that weight come from?
Losing 20 kilograms consisting overwhelmingly of fat is biologically different from losing the same amount with substantially more skeletal-muscle loss.
That is why body composition is attracting so much research attention.
What other muscle-preserving drugs are being studied?
The pipeline is expanding rapidly.
Current research includes different approaches involving:
Trevogrumab — myostatin inhibition
Apitegromab — selective inhibition of myostatin activation
Bimagrumab — activin type II receptor blockade
Taldefgrobep alfa — myostatin/activin pathway inhibition
Enobosarm — selective androgen receptor modulation
Researchers are therefore approaching the same broad problem through several different biological mechanisms.
What happens next?
The key question isn’t simply whether trevogrumab increases a lean-mass measurement.
Researchers now need to establish whether preserving muscle produces meaningful improvements in outcomes that actually matter.
Does strength improve?
Does physical function improve?
Are older adults better protected?
Can sarcopenia risk be reduced?
Does body composition remain different over the long term?
And can those effects be achieved with acceptable safety?
Those questions will determine whether muscle-preserving compounds become an important complement to incretin medicines or remain primarily an interesting research concept.
The bigger picture
Metabolic research appears to be entering another stage.
We’ve moved from trying to produce greater weight reduction through increasingly powerful incretin combinations towards asking a more sophisticated question:
Can researchers control
what kind of weight
is lost?
Trevogrumab is one of the clearest examples of this change.
Rather than competing directly with GLP-1 medicines, compounds targeting myostatin could potentially be investigated alongside them, with one mechanism driving weight reduction and another influencing body composition.
Whether that strategy ultimately translates into better long-term outcomes remains to be established.
But as of October 2026, muscle preservation is unquestionably becoming one of the most important emerging areas of metabolic research.
At Klarity Research, we’ll continue following this changing field as new clinical evidence emerges.
For educational and research information only. This article is not medical advice.