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Fat Loss Without Muscle Loss? Bimagrumab, Activin Blockade and the Next Muscle-Preserving Peptides

Short answer: the next step in obesity research is to pair a GLP-1 with a second drug that protects muscle . The most advanced candidate is bimagrumab , Eli Lilly’s antibody that blocks activin type II receptors . In the Phase 2b BELIEVE trial, bimagrumab plus semaglutide produced ~22% weight loss versus ~16% for semaglutide alone. Nearly all of the combination’s loss was fat. Rivals include apitegromab, trevogrumab and enobosarm. One honest caveat: the leaders are antibodies and small molecules, not peptides . Peptide-class approaches are earlier and mostly preclinical. None of these combinations is approved.

Plain-English summary. Semaglutide and tirzepatide are approved medicines; every other compound named here is investigational. This page is general information, not medical advice. Do not use unapproved compounds on people.

The problem these drugs are trying to solve

GLP-1 drugs produce large weight loss, and part of that loss is lean mass. Roughly a quarter to two-fifths of it is lean mass, depending on the trial (see GLP-1s and Muscle Loss). The goal of the add-on drugs is simple to state: more of the loss from fat, less from muscle . Ideally, strength and function hold up too.

The biology: myostatin, activin and the brake on muscle

Muscle growth has a built-in brake. A family of signalling proteins, chiefly myostatin (GDF-8), activin A and GDF-11 , binds activin type II receptors (ActRIIA and ActRIIB) on muscle cells. Through SMAD2/3 signalling, that holds muscle mass in check. Animals born without functional myostatin are strikingly muscular, which is why the pathway has been a drug target for two decades.

There are several places to release the brake:

Block the receptor (bimagrumab). This is the broadest approach: it silences several ligands at once.

Block one ligand , such as myostatin (trevogrumab) or activin A (garetosmab).

Stop myostatin from being activated (apitegromab). This targets the latent precursor and is the most selective approach.

Mop up the ligands . This is what the body’s own binding protein, follistatin , does naturally.

Bimagrumab and the BELIEVE trial

Bimagrumab was first developed at Novartis and later moved to Versanis, which Eli Lilly acquired in 2023. The Phase 2b BELIEVE trial tested it alone and with semaglutide in adults with overweight or obesity. The results were presented at the American Diabetes Association meeting in June 2025 and published in full in Nature Medicine in March 2026. Bimagrumab was given intravenously in this trial.

Arm Mean weight loss Body-composition headline Bimagrumab + semaglutide ~22.1% ~93% of weight lost was fat Semaglutide alone ~15.7% Larger share lost as lean mass Bimagrumab alone ~10.8% Fat loss with lean mass largely preserved

Lilly is now testing bimagrumab with tirzepatide in Phase 2 trials, both in adults with obesity and in adults with obesity and type 2 diabetes. Those trials use subcutaneous dosing. No results from them had been published as of November 2026.

The rest of the field

Candidate Developer Class Target Partner drug studied Bimagrumab Eli Lilly Antibody Activin type II receptors Semaglutide; tirzepatide Apitegromab Scholar Rock Antibody Latent pro-myostatin Tirzepatide (EMBRAZE) Trevogrumab ± garetosmab Regeneron Antibodies Myostatin; activin A Semaglutide (COURAGE) Enobosarm Veru Small molecule (SARM) Androgen receptor Semaglutide (QUALITY)

Each of these Phase 2 programmes has reported less lean-mass loss than the GLP-1 alone. The details differ, and so do the warnings. Regeneron’s triple combination with garetosmab raised safety and tolerability signals that the dual combination did not. Most of these trials are small and short. They measure lean mass on scans more reliably than they measure strength or function.

Where peptides fit and where they do not yet

The title asks about the next muscle-preserving peptides , and the honest answer is that the front-runners are not peptides. Antibodies dominate because they last for weeks in the body and bind their targets tightly. Peptide-class work on the same pathway exists but is earlier:

Follistatin and follistatin-derived fragments: the natural ligand trap. Follistatin itself is a glycoprotein. Most primate and rodent work used gene delivery of the FST344 isoform rather than injected protein.

Myostatin-inhibiting peptides: short sequences derived from the myostatin propeptide or from follistatin, studied in cell and animal models.

Incretin design itself: newer multi-agonist peptides are being compared on body composition, not just total weight. That is a quieter way peptide chemistry may improve weight-loss quality.

So the realistic near-term picture is a peptide GLP-1 plus an antibody add-on . Fully peptide-based muscle protection remains a research question.

What to watch next

The bimagrumab + tirzepatide Phase 2 readouts.

Whether lean-mass gains on scans translate into strength and function .

Safety at scale, especially for broad receptor blockade.

Whether regulators accept body composition as a meaningful endpoint for an obesity add-on.

Research-compound context

Bimagrumab, apitegromab, trevogrumab, garetosmab and enobosarm are proprietary investigational drugs. New-U does not sell them. The related laboratory references New-U Research Compounds catalogues are:

Tirzepatide and semaglutide : the incretin references used in the combination trials above, each with the per-batch Certificate of Analysis published online.

Follistatin-344 : the FST344 isoform studied in myostatin-antagonism research. No analytical report has been published for it yet, and nothing here suggests it preserves muscle.

Research use only, not for human consumption.

Frequently Asked Questions

What is bimagrumab? An investigational monoclonal antibody, originated at Novartis and now developed by Eli Lilly, that blocks activin type II receptors, which carry signals from myostatin, activin A and related proteins that limit muscle growth. It is being studied alongside GLP-1 drugs to shift weight loss toward fat.

What did the BELIEVE trial show? In the Phase 2b BELIEVE trial, bimagrumab plus semaglutide produced about 22% mean weight loss, compared with about 16% on semaglutide alone. Nearly all of the combination's weight loss came from fat, while lean mass was largely preserved.

Is bimagrumab a peptide? No. Bimagrumab is a full-size antibody. Most of the leading muscle-preserving candidates are antibodies or small molecules; peptide-class approaches, such as follistatin-derived and myostatin-inhibiting peptides, are at an earlier, mostly preclinical stage.

Is any muscle-preserving add-on approved? No. As of November 2026 none of these candidates is approved for use with GLP-1 drugs. Bimagrumab plus tirzepatide is still in Phase 2 trials.

Does New-U sell bimagrumab? No. Bimagrumab, apitegromab and the other candidates are proprietary drugs. New-U Research Compounds catalogues follistatin-344 as laboratory research material only. It is not a muscle-preservation product and is not for human use.

Primary sources & further reading

ClinicalTrials.gov — NCT06643728: bimagrumab and tirzepatide in adults with obesity or overweight

ClinicalTrials.gov — NCT06901349: bimagrumab and tirzepatide in obesity with type 2 diabetes

Heymsfield SB et al. — Bimagrumab and semaglutide in adults with obesity (BELIEVE), Nature Medicine 2026

U.S. National Library of Medicine — PubMed: myostatin/activin inhibition and lean mass

ClinicalTrials.gov — apitegromab trial registry

External links are provided for research reference only; New-U is not affiliated with the cited organisations and links carry no endorsement either way.

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Lab-Verified Incretin Research References

New-U Research Compounds catalogues the incretin references tirzepatide and semaglutide as lyophilised laboratory material, with the per-batch Certificate of Analysis published online. Research use only - all claims made on this site are for testing and research use only.

Research-grade · >99% HPLC purity · COA per lot

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