Drugs studied to preserve muscle on GLP-1s: bimagrumab, enobosarm, and the activin–myostatin approach

A consistent finding across the GLP-1 receptor agonist class is that a meaningful fraction of the weight lost — roughly 30–40% in published trials — is fat-free mass rather than fat. The companion articles cover the trial data (GLP-1 and lean mass loss) and the physiology of why it happens (why GLP-1 drives lean mass loss). The short version: these compounds do not act on muscle directly — they create a large appetite-driven energy deficit, and the body meets part of that deficit from muscle protein unless resistance training and adequate protein intervene.

The most robustly evidence-supported way to blunt that lean-mass loss remains non-pharmacological — progressive resistance training and protein intake of at least 1.6 g/kg/day, set out with protocol parameters in the companion article. This page covers a different and newer line of research: a class of investigational drugs being studied specifically to preserve muscle while a GLP-1 agonist drives the weight loss. The two most advanced are an antibody that blocks the activin/myostatin pathway (bimagrumab) and an oral selective androgen receptor modulator, or SARM (enobosarm).

Scope and status. Every agent discussed here is investigational. None is approved for muscle preservation during weight loss in Australia or elsewhere as of this writing, and both were studied in combination with semaglutide — neither has been tested with retatrutide. RetaLABS does not supply bimagrumab or enobosarm. This is an informational research reference. It is not medical advice and makes no therapeutic, efficacy, or dosing recommendation.

Bimagrumab is a first-in-class monoclonal antibody that targets activin type II receptors (ActRII) — the receptors through which myostatin and activin A signal. Myostatin is a negative regulator of muscle growth; blocking its pathway shifts the balance toward muscle preservation (and can increase muscle), while also promoting loss of fat. The mechanism is therefore complementary to GLP-1 agonism rather than overlapping with it.

The data came from BELIEVE, a randomised, double-blind, placebo-controlled Phase 2b trial in 507 adults with overweight or obesity, presented at the 2025 American Diabetes Association Scientific Sessions (lead investigator Steven Heymsfield, Pennington Biomedical Research Center) and published in Nature Medicine (2026). Participants received semaglutide (1.0 or 2.4 mg weekly) and/or intravenous bimagrumab at two dose levels (infusions at weeks 4, 16, 28 and 40), alone or in combination, over 72 weeks.

The combination produced the greatest total weight loss (22.1% vs 15.7% for semaglutide alone) while directing 92.8% of that loss to fat mass. It also limited lean-mass loss to 2.9% versus 7.4% with semaglutide alone — and bimagrumab on its own slightly increased lean mass (+2.5%). On responder measures, 69.8% of the combination group achieved at least 20% body-weight reduction (vs 25.0% for semaglutide alone and 10.9% for bimagrumab alone), and 94.0% achieved at least a 30% reduction in fat mass (vs 36.4% and 50.0%). The combination also produced a statistically significant improvement in SF-36 Physical Functioning versus semaglutide 2.4 mg alone. Reported adverse events were consistent with each drug's known profile (muscle spasms, diarrhoea and acne with bimagrumab; nausea, diarrhoea, constipation and fatigue with semaglutide), with about 9% of combination-treated participants discontinuing due to adverse events over 72 weeks and no deaths. Bimagrumab's developer (Versanis) was acquired by Eli Lilly, which is continuing its development.

Enobosarm is an oral, once-daily selective androgen receptor modulator (SARM). SARMs are designed to activate androgen receptors in muscle and bone with the aim of more tissue-selective effects than anabolic steroids. The rationale for pairing it with a GLP-1 agonist is to defend lean mass through anabolic signalling while the GLP-1 drives the energy deficit — an approach specifically aimed at sarcopenic obesity in older adults, who carry a higher baseline risk of low muscle mass.

The developer (Veru) reported topline results from QUALITY, a Phase 2b multicentre, double-blind, placebo-controlled trial of enobosarm 3 mg and 6 mg versus placebo in 168 adults aged 60 or older who were overweight or had obesity and were receiving Wegovy (semaglutide). Per the company's topline disclosure (January 2025), the trial met its primary endpoint:

• A 71% reduction in the loss of lean mass versus placebo across enobosarm patients at 16 weeks (P = .002) — the primary endpoint.
• Total body-weight change was similar between groups (−4.7 kg enobosarm vs −4.4 kg placebo), but a 70.5% reduction in the share of weight lost as lean mass meant the loss was directed more selectively at fat; enobosarm also showed 27% greater fat-mass loss than placebo (P = .096).
• The preserved muscle translated into function: roughly 54.5% fewer enobosarm patients had a clinically significant (≥10%) decline in stair-climb power versus placebo.
• Enobosarm did not increase gastrointestinal adverse events — relevant given the GI burden of GLP-1 therapy.

The FDA has provided guidance on enobosarm's regulatory path and a Phase 3 design with stair-climb power over 52 weeks as the proposed primary objective; a follow-on Phase 2b trial (PLATEAU) in older adults is underway.

An important regulatory and safety note on SARMs. Enobosarm is investigational and not approved by the TGA or FDA for muscle preservation, weight management, or any other indication. SARMs as a class are prohibited in sport by the World Anti-Doping Agency, and products sold online as "SARMs" are frequently mislabelled or adulterated. Nothing here endorses SARM use; this is a description of one investigational agent in a controlled clinical-trial context. RetaLABS does not supply enobosarm or any SARM.

Bimagrumab and enobosarm are the most advanced examples of a broader research direction that 2026 review literature now treats as a distinct field — pharmacological preservation of lean mass during incretin-based weight loss (for a neutral overview, see "Muscle-preserving therapies in the era of pharmacological weight loss", Obesity and Endocrinology 2026). The approaches under investigation fall into a few mechanistic groups:

Several caveats apply across the whole area. The drug trials to date have been Phase 2 — sized for signal, not definitive outcomes — and were run with semaglutide, the single-receptor GLP-1 agonist. Neither has been tested with retatrutide, whose own glucagon-receptor component is separately hypothesised to influence body composition (a question that is itself unresolved — see the body-composition data). Whether a pharmacological muscle-preserving benefit is durable, safe over the long term, and meaningful for hard functional outcomes will require Phase 3 data that does not yet exist.

What the evidence supports today. For anyone weighing the research literature, the most reliably supported lean-mass modifiers during GLP-1 weight loss remain resistance training and adequate protein, covered with protocol detail in GLP-1 and lean mass loss. The pharmacological agents on this page are an emerging, investigational complement to — not a replacement for — that evidence base.

RetaLABS supplies research-grade GLP-1-class peptides (semaglutide, tirzepatide, retatrutide) for laboratory research use only. RetaLABS does not supply bimagrumab, enobosarm, or any SARM, and makes no therapeutic claim about any of them. This page is an informational research reference compiled from the cited trial disclosures and is not medical advice. A foreign development or approval status does not confer Australian (TGA) approval.

Continue across the cluster: GLP-1 and lean mass loss (trial data + preservation protocols) · Why GLP-1 drives lean mass loss (the mechanism) · Retatrutide Research Guide · Glucagon receptor explained.