GLP-1 drugs settled how much weight comes off. The open question now is what kind — because a large share of that loss is muscle, not fat. This is the research frontier built to keep the muscle: the activin/myostatin axis, and the antibodies being tested on top of the incretins.
Research reference only. Not medical advice, dosing guidance, or an offer for sale.
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Weight on a scale is fat and muscle together. When weight comes off fast, some muscle goes with it — and the incretin drugs come off fast. Across trial body-composition substudies, lean tissue makes up roughly a quarter to 40% of the total weight lost on semaglutide and tirzepatide. That’s in the same range as diet-based weight loss, but it is now happening at the scale of tens of millions of people, and over a lifetime of use rather than a diet.
Muscle is not cosmetic. It is where the body burns glucose, the reserve that protects against falls and frailty with age, and part of why weight regain after stopping tends to come back as fat. So the next chapter of the field is not a bigger number on the scale — it is a better composition of the loss.
A typical GLP-1 weight-loss split
Proportions vary by drug, dose, and study — tirzepatide’s SURMOUNT-1 DXA substudy put lean mass near the low end (~25%), while some semaglutide substudies land higher. The goal of the agents below is to shrink the right-hand bar.
Nearly every muscle-preservation agent acts somewhere along this single signaling path — the body’s brake on muscle growth
Ligand-neutralizing antibody
Binds the mature growth factor in circulation before it reaches the receptor. The most direct block — one ligand at a time.
Precursor-selective antibody
Binds the inactive pro/latent form of myostatin and blocks its activation — a selectivity meant to spare related factors like GDF11 and the activins.
Receptor-level blocker
Blocks the shared ActRII receptor itself, shutting off myostatin and activin signaling at once — the broadest mechanism, and the one that most reliably adds muscle.
Natural antagonist
Follistatin is the body’s own brake-release: it sequesters myostatin and activin away from the receptor. Studied as a protein and, more potently, as a gene-therapy payload.
Four independent Phase 2 programs, one direction: keep the muscle, shift the loss onto fat
Trevogrumab + semaglutide
COURAGE · Phase 2 (Regeneron)~35% of semaglutide-alone weight loss was lean mass; adding trevogrumab preserved an estimated 50–80% of it while deepening fat loss.
+ garetosmab (the triplet)
COURAGE · Phase 2 (Regeneron)The trevogrumab + garetosmab triplet preserved ~80.9% of the lean mass semaglutide alone would have cost — the best profile, but with more tolerability-driven dropouts.
Apitegromab + tirzepatide
EMBRAZE · Phase 2 (Scholar Rock)Tirzepatide alone lost 30% of weight as lean mass; apitegromab preserved 54.9% of it (~1.9 kg / 4.2 lb), and was generally well tolerated.
Bimagrumab + semaglutide
Phase 2 (Lilly / Versanis)The combination reached ~22.1% weight loss with ~92.8% of it from fat, versus 71.8% fat for semaglutide alone; bimagrumab alone lost ~10.8% essentially all from fat.
The through-line: in every readout, blocking the axis on top of a GLP-1 drug moved the loss off muscle and onto fat. The gains are real and consistent — and they come from Phase 2 trials, not approvals. The open questions are durability, function (does preserved mass mean preserved strength?), and tolerability.
Garetosmab
Activin A · Regeneron
Approved as Pasatru in August 2026 for the rare bone disease FOP — the first drug of the entire axis to reach the market. Its obesity and muscle-preservation use is investigational; it is the activin-A leg of the COURAGE triplet.
Apitegromab
Pro/latent myostatin · Scholar Rock
EMBRAZE preserved 54.9% of the lean mass otherwise lost on tirzepatide. Its spinal-muscular-atrophy application, resubmitted after a facility-related CRL, has an FDA decision date of Sept 30, 2026.
Trevogrumab
Mature myostatin · Regeneron
The COURAGE workhorse — preserved an estimated 50–80% of otherwise-lost lean mass added to semaglutide, and the most-studied muscle-sparing add-on in the incretin era.
Bimagrumab
ActRII receptor · Lilly / Versanis
Fat down and muscle up — an unusual profile that drew a ~$2B acquisition. Lilly ended its tirzepatide combination in type 2 diabetes in 2025 (portfolio priority, not safety); a non-diabetic obesity study continues toward a 2026 readout.
Emugrobart
Pro/latent myostatin (sweeping) · Roche / Chugai
A "sweeping" antibody engineered to actively clear myostatin, not just block it. Its SMA and FSHD programs were dropped in 2026 after the MANATEE trial missed — though the company said the obesity rationale still stood.
This is a frontier, and it reads like one. The mechanism is unusually clean — a single brake, several ways to release it — and the early data point the same direction. But no agent is approved to preserve muscle during weight loss. The one axis drug that has reached the market, garetosmab (Pasatru), is approved for a rare bone disease, not obesity. Bimagrumab’s most-watched combination was shelved for portfolio reasons. The story is genuinely promising and genuinely unfinished.
It is also a hype magnet. “Myostatin blockers” are marketed well ahead of the evidence, the antibodies here are not sold as research peptides, and the pathway is banned in sport. The biology worth knowing is real — start with myostatin and its natural antagonist follistatin — but the drugs are investigational, not a shortcut you can order.
Do GLP-1 drugs like Ozempic and Zepbound cause muscle loss?
Some lean-mass loss accompanies the large weight loss they produce. Across trial body-composition substudies, lean tissue accounts for roughly a quarter to 40% of the total weight lost on semaglutide and tirzepatide — proportions broadly similar to diet-induced weight loss, but now happening at the scale of tens of millions of people. This page is a research reference, not medical advice.
What is being developed to preserve muscle during weight loss?
The leading strategy targets the activin/myostatin axis — the body’s brake on muscle growth. Antibodies against myostatin (trevogrumab, apitegromab) or activin A (garetosmab), and the receptor-level blocker bimagrumab, are being tested on top of GLP-1 drugs. Myostatin and follistatin are the underlying biology; follistatin gene therapy is a separate, earlier-stage approach.
How much muscle can these agents actually preserve?
In the Phase 2 COURAGE trial, adding trevogrumab to semaglutide preserved an estimated 50–80% of the lean mass otherwise lost, and the trevogrumab-plus-garetosmab triplet preserved about 80.9% (with more tolerability dropouts). In the Phase 2 EMBRAZE trial, apitegromab preserved 54.9% of the lean mass otherwise lost on tirzepatide. These are Phase 2 results, not approvals.
What is myostatin, and why does blocking it build muscle?
Myostatin (GDF-8) is a growth factor that limits skeletal-muscle mass — the body’s brake on muscle. It signals through the activin type II receptors and the Smad2/3 pathway. Removing or blocking it releases the brake and increases muscle, which is why the whole field is built around inhibiting the pathway rather than supplying the factor.
Are any muscle-preservation drugs FDA-approved?
Not for muscle preservation. Garetosmab (Pasatru) was FDA-approved in August 2026 for the rare bone disease FOP — the first agent of the axis to reach the market — and apitegromab is under FDA review for spinal muscular atrophy. Every obesity and muscle-preservation use here is investigational. The pathway is also banned in sport.
Can I buy these to preserve muscle on a GLP-1?
No. These are monoclonal antibodies studied in clinical trials, not research peptides available from vendors, and none is approved for muscle preservation. This page catalogs the science and the pipeline; it is not medical advice, dosing guidance, or an offer for sale.
Research reference only. Except for garetosmab (approved for FOP only), none of the agents on this page are FDA-approved, and none is approved to preserve muscle during weight loss. Nothing here is medical advice, dosing guidance, or an offer for sale.