Bimagrumab (research code BYM338) is a fully human monoclonal antibody that blocks the activin type II receptors (ActRIIA and ActRIIB). These receptors carry the “stop growing” signal of myostatin, activin A and related proteins in muscle, and activin signals in fat tissue. Blocking them makes muscle grow and fat shrink at the same time, which is why the drug is discussed as a way to keep muscle during weight loss.
Novartis developed bimagrumab for muscle-wasting conditions. In those trials it reliably added lean mass but did not improve walking or physical function. Eli Lilly acquired it in 2023 and now studies it for obesity, alone and with GLP-1-based drugs. It is not approved anywhere, it is given by infusion or injection in trials only, and it is banned in sport under WADA class S4.3.
This page summarizes what the published clinical trials, trial registries and regulators report. It is for education only and is not medical advice.
| Property | Detail |
|---|---|
| Drug class | Fully human monoclonal antibody against activin type II receptors (ActRIIA and ActRIIB) |
| Other names | BYM338 (Novartis); LY3985863 (Lilly) |
| Developers | Novartis (discovery); Versanis Bio; Eli Lilly (acquired 2023) |
| Route in trials | Intravenous infusion in published trials; subcutaneous in Lilly’s current trials |
| Doses studied | 10 or 30 mg/kg IV every 12 weeks (obesity); 10 mg/kg IV every 4 weeks (type 2 diabetes); 700 mg IV monthly (sarcopenia) |
| Half-life | Not established: clearance is nonlinear (target-mediated), so a single half-life could not be calculated |
| Approval status | Investigational; not approved by the FDA or any other regulator |
| US controlled substance | Not listed in Schedule III |
| WADA status | Prohibited at all times (S4.3, named explicitly) |
What it is
Bimagrumab is an antibody, not a peptide or a steroid. It is a large protein that binds the activin type II receptors on cells and stops their natural ligands from docking (Lach-Trifilieff et al., Mol Cell Biol 2014). Those ligands include:
- myostatin, the best-known brake on muscle growth;
- activin A and GDF11, which signal through the same receptors;
- activin E, which acts on fat tissue through a partner receptor called ALK7 (Heymsfield et al., Nat Med 2026).
Because it blocks the receptor rather than one ligand, it shuts off several brakes at once. In the original Novartis work, bimagrumab enlarged muscle in mice more than a myostatin-only inhibitor did, and a mouse version of the antibody still grew muscle in mice that already lacked myostatin. In cell culture, it blocked the muscle-wasting effects of myostatin and activin A (Lach-Trifilieff et al., Mol Cell Biol 2014).
The fat effect is a direct action on fat tissue, not appetite suppression. The BELIEVE trial authors note that bimagrumab “does not appear to affect food intake” and instead increases fat breakdown by blocking activin signals in adipose tissue (Heymsfield et al., Nat Med 2026). This is the opposite of semaglutide and tirzepatide, which work mainly by reducing appetite.
How it differs from related compounds
The library has pages on other ways to block the same pathway. They differ in what they bind:
| Compound | What it is | Target |
|---|---|---|
| Bimagrumab | Monoclonal antibody | The receptors themselves (ActRIIA and ActRIIB) |
| Follistatin-344 | Natural binding protein | Circulating myostatin and activins |
| ACE-083 | Follistatin-based fusion protein, injected into one muscle | Myostatin, activins and related ligands, locally |
Pharmacokinetics
As a large antibody, bimagrumab is not taken by mouth. Key findings from the phase 1 studies:
| Finding | Result | Source |
|---|---|---|
| Peak level after a single 30 mg/kg IV dose (older adults) | 982 μg/mL | Rooks et al., JCSM 2020 |
| Peak level after 30 mg/kg IV (adults with obesity) | 944 μg/mL; profile similar to older adults | Rooks et al., JCSM 2020 |
| Clearance | Nonlinear, driven by binding to its receptor target | Rooks et al., JCSM 2020 |
| Half-life | Could not be derived with standard analysis | Rooks et al., JCSM 2020 |
| Subcutaneous bioavailability | About 40% | Petricoul et al., Clin Pharmacokinet 2023 |
The nonlinear clearance means that the drug is removed partly by binding to its own receptors, so higher doses stay in the blood disproportionately longer. In the single-dose study, the lean-mass gain lasted longer after 30 mg/kg than after 3 mg/kg.
A phase 1 study in 91 adults aged 70 and over compared monthly IV infusions with weekly subcutaneous injections. Weekly subcutaneous dosing gave drug levels and effects comparable with monthly IV dosing: lean mass rose 4–6% (1.5–2 kg) with every regimen except the lowest dose (52.5 mg), and fat mass fell about 2–3 kg (Petricoul et al., Clin Pharmacokinet 2023). Lilly’s newer trials use the subcutaneous route.
Development and regulatory status
- Novartis era (2011–2019). Phase 2 and 2b/3 trials in inclusion body myositis, sarcopenia, hip fracture recovery, COPD, cancer-related weight loss and type 2 diabetes with obesity (ClinicalTrials.gov listing).
- Versanis and Lilly (2021–present). Versanis Bio took the drug into obesity trials. Lilly agreed to acquire Versanis in July 2023 for up to $1.925 billion, describing bimagrumab as its lead asset (Lilly/Versanis press release).
- Current trials. A phase 2 trial of subcutaneous bimagrumab with tirzepatide in obesity without diabetes enrolled 252 people and finished its primary data collection in January 2026 (NCT06643728). A planned phase 2b trial in people with type 2 diabetes was withdrawn before enrolling anyone “for strategic business reasons” (NCT06901349).
No regulator has approved bimagrumab for any use. It is not one of the anabolic steroids named in the US Schedule III list (21 CFR 1308.13), but as an unapproved biologic it is available legitimately only inside clinical trials.
What the research shows
Across every trial, the same pattern appears: lean mass goes up and fat mass goes down. Whether that translates into better function or health depends on the population.
Obesity with semaglutide (BELIEVE)
The largest trial randomized 507 adults with obesity (average weight 107.5 kg) to nine groups for 48 weeks. The groups received placebo, IV bimagrumab (10 or 30 mg/kg every 12 weeks), weekly semaglutide (1.0 or 2.4 mg), or combinations, followed by an open-label extension to week 72 (Heymsfield et al., Nat Med 2026).
Week 48 results for the main groups (treatment-regimen analysis):
| Group | Body weight | Total fat mass | Total lean mass |
|---|---|---|---|
| Placebo | −3.3 kg | −5.6% | −0.9% |
| Bimagrumab 30 mg/kg | −9.3 kg | −13.0% to −18.9% (bimagrumab arms) | +1.0% to +1.1% (bimagrumab arms) |
| Semaglutide 2.4 mg | −14.2 kg | −16.0% to −21.1% (semaglutide arms) | −4.7% to −6.9% (semaglutide arms) |
| Bimagrumab 30 mg/kg + semaglutide 2.4 mg | −17.8 kg | −24.7% to −33.7% (combination arms) | −0.8% to −2.3% (combination arms) |
Key points from the trial:
- Share of weight lost as fat. At week 48 it was 100% with bimagrumab 30 mg/kg, 71.1% with semaglutide 2.4 mg, and 92.3% with the high-dose combination.
- Week 72. Weight loss reached −12.0 kg (−10.8%) with bimagrumab 30 mg/kg, −16.5 kg (−15.7%) with semaglutide 2.4 mg and −24.2 kg (−22.1%) with the combination. Fat mass fell by 28.5%, 27.8% and 45.7%, respectively.
- Visceral fat (fat around the organs) fell more in the combination groups than with semaglutide alone.
- Grip strength improved significantly only in the bimagrumab 30 mg/kg plus semaglutide 1.0 mg group (+4.8 kg vs +1.7 kg on placebo).
On its own, bimagrumab produced less weight loss than semaglutide, because it added muscle while removing fat. Its main promise is in combination, where it shifted the weight lost toward fat.
Type 2 diabetes with obesity
A 48-week phase 2 trial randomized 75 adults with type 2 diabetes (average BMI 32.9) to IV bimagrumab 10 mg/kg (up to 1,200 mg) every 4 weeks or placebo. Both groups received diet and exercise counseling (Heymsfield et al., JAMA Netw Open 2021):
| Outcome at week 48 | Bimagrumab | Placebo |
|---|---|---|
| Total fat mass | −7.5 kg (−20.5%) | −0.18 kg (−0.5%) |
| Lean mass | +1.70 kg (+3.6%) | −0.4 kg (−0.8%) |
| Waist circumference | −9.0 cm | +0.5 cm |
| HbA1c (long-term blood sugar) | −0.76 percentage points | −0.04 percentage points |
| Body weight | −5.9 kg (−6.5%) | −0.8 kg (−0.8%) |
Only the 58 participants (77%) who completed treatment were analyzed, and the confidence intervals reported were 80%, not the usual 95%.
A 2026 meta-analysis pooled 4 placebo-controlled trials with 268 participants who had obesity, insulin resistance or type 2 diabetes (Shao et al., Diabetes Obes Metab 2026). Compared with placebo, bimagrumab:
- reduced weight by 4.85 kg (95% CI 2.88–6.82) and fat mass by 4.72 kg (95% CI 1.40–8.05);
- increased lean mass by 1.66 kg (95% CI 0.81–2.51);
- lowered HbA1c by 0.13 percentage points;
- raised LDL cholesterol by 0.47 mmol/L (≈ 18 mg/dL).
Sarcopenia and older adults
Sarcopenia is age-related loss of muscle mass and function. Here bimagrumab built muscle but did not make people move better than diet and exercise alone:
- Proof-of-concept trial (n = 40, aged 65 and over). A single 30 mg/kg IV dose raised thigh muscle volume by 8.0% at week 8 vs 0.4% with placebo. Gait speed and walking distance improved only in the slowest walkers (Rooks et al., J Am Geriatr Soc 2017).
- Larger trial (n = 180, aged 70 and over, 38 sites). Bimagrumab 700 mg monthly for 6 months, on top of adequate diet and home exercise, increased lean body mass by 7% vs 1% with placebo. The main outcome, a physical performance score (SPPB), rose by 1.34 vs 1.03 points, which was not significant (p = 0.13). Both groups improved (Rooks et al., JAMA Netw Open 2020).
Hip fracture, COPD and inclusion body myositis
The same gap between muscle mass and function appeared in three other diseases:
| Trial | Design | Muscle result | Function result |
|---|---|---|---|
| Hip fracture recovery (Hofbauer et al., Lancet Healthy Longev 2021) | 250 adults aged 60 and over; placebo or 70, 210 or 700 mg IV every 4 weeks for 24 weeks | Lean mass +1.9 kg (210 mg) and +2.8 kg (700 mg) vs +0.2 kg | No improvement in gait speed or SPPB |
| COPD with low muscle mass (Polkey et al., AJRCCM 2019) | 67 patients; two 30 mg/kg IV doses or placebo | Thigh muscle volume +5.0% vs −1.3% at week 24 | No significant gain in 6-minute walk distance |
| Inclusion body myositis, RESILIENT (Hanna et al., Lancet Neurol 2019) | 251 patients; 1, 3 or 10 mg/kg IV every 4 weeks or placebo for at least 48 weeks | — | 6-minute walk distance not different from placebo at any dose |
The two-year RESILIENT extension (211 participants) also found no mobility benefit, and it was stopped early (Amato et al., Neurology 2021). These results ended the drug’s development for muscle diseases.
Healthy young men after immobilization
In 24 healthy young men whose leg was put in a cast for 2 weeks, one 30 mg/kg IV dose after cast removal raised thigh muscle volume to 5.1% above the pre-cast level at 12 weeks. With placebo, volume only returned to baseline (−0.1%). Strength did not differ: knee strength returned to pre-cast levels within 6 weeks in both groups (Rooks et al., JCSM 2017). There are no trials in trained athletes.
Animal data
In mice with diet-induced obesity, bimagrumab added about 10% lean mass, and combined with semaglutide it gave more fat loss while keeping lean mass (Nunn et al., Mol Metab 2024). A different mouse study using an ActRIIA/IIB-blocking antibody found glucose intolerance, enlarged hearts with glycogen build-up, more liver fat and less voluntary running. The authors point out that this conflicts with the improved blood sugar seen in humans and may reflect species differences (Carlsson et al., Mol Metab 2025).
“Muscle growth without hormones.” Bimagrumab does not act through the androgen receptor. In healthy adults aged 55–75 it did not change testosterone or adrenal androgens. It did lower FSH in women, because activin also controls the pituitary (Garito et al., Clin Endocrinol 2018). More muscle on a scan has also not meant better function in any patient trial so far.
Side effects and risks
Common side effects
Muscle spasms (mostly cramps), diarrhea and acne are the consistent side effects. Rates in BELIEVE during the first 48 weeks (Heymsfield et al., Nat Med 2026):
| Adverse event | Placebo | Bimagrumab 10 mg/kg | Bimagrumab 30 mg/kg | Bimagrumab 30 mg/kg + semaglutide 2.4 mg |
|---|---|---|---|---|
| Muscle spasms | 5.5% | 46.4% | 73.7% | 63.6% |
| Diarrhea | 5.5% | 41.1% | 49.1% | 49.1% |
| Acne | 3.6% | 33.9% | 43.9% | 52.7% |
| Serious adverse events | 3.6% | 12.5% | 8.8% | 7.3% |
| Stopped treatment due to adverse events | 3.6% | 21.4% | 14.0% | 5.5% |
In the 2021 diabetes trial, muscle spasms affected 41% vs 3% on placebo, and diarrhea 41% vs 11% (Heymsfield et al., JAMA Netw Open 2021). In RESILIENT, muscle spasms affected 40–68% across doses vs 21% on placebo (Hanna et al., Lancet Neurol 2019). In the 2026 meta-analysis, bimagrumab raised the risk of muscle spasms about tenfold (RR 10.44), diarrhea about fivefold (RR 4.91), and stopping treatment early about sixfold (RR 5.75) (Shao et al., Diabetes Obes Metab 2026).
Cholesterol
Bimagrumab raises total and LDL cholesterol. In BELIEVE, LDL rose in the first 12 weeks in all bimagrumab groups. At week 72, LDL was 17.6% above baseline with bimagrumab alone, while it was back near baseline (+0.1%) in the group that also took semaglutide 2.4 mg (Heymsfield et al., Nat Med 2026). The long-term cardiovascular meaning of this is unknown.
Lab changes, pancreas and bone
In BELIEVE, bimagrumab groups also showed:
- rises in alkaline phosphatase and creatine kinase;
- temporary rises in the liver enzymes ALT and AST;
- a temporary rise in lipase, a pancreatic enzyme;
- lower magnesium, though it stayed within the normal range.
Pancreatitis was uncommon and balanced across groups. In the 2021 diabetes trial, one case of pancreatitis and one case of raised lipase with abdominal pain (later traced to gallstones) occurred on bimagrumab (Heymsfield et al., JAMA Netw Open 2021). Hip bone density fell by about 2% with semaglutide 2.4 mg and in most combination groups, vs 0.8% with placebo. The authors suggest this may reflect less load on the bones after weight loss (Heymsfield et al., Nat Med 2026).
Heart
Because myostatin pathway blockers grow skeletal muscle, a key question is whether they also enlarge heart muscle. In a 6-month randomized trial in 68 healthy adults aged 60–86, bimagrumab 10 mg/kg IV did not meaningfully change left ventricular mass or ejection fraction on cardiac MRI (Rooks et al., JCEM 2026). RESILIENT also found no significant cardiac effects on ECG or echocardiography. Longer and larger studies are still lacking.
Hormones
In women aged 55–75, bimagrumab lowered FSH by about 42 IU/L at week 8 compared with placebo. The change reversed once the drug was cleared. Testosterone and adrenal androgens did not change in men or women (Garito et al., Clin Endocrinol 2018). Effects on fertility and pregnancy have not been established.
Legal status and use outside medicine
- Sport. The WADA 2026 Prohibited List bans “agents preventing activin receptor IIB activation” at all times under S4.3 and names bimagrumab as an example. WADA classes S4.3 substances as non-specified.
- United States. Bimagrumab is not a scheduled controlled substance, but it is an unapproved investigational drug. No approved product exists outside clinical trials.
Key takeaways
- A receptor-blocking antibody, not a peptide or steroid. It blocks ActRIIA and ActRIIB, shutting down myostatin, activins and related brakes on muscle, and also acts directly on fat tissue.
- Reliable body-composition effects. Trials consistently show lean mass gains of about 1–7% and substantial fat loss, including visceral fat.
- Strongest data are in obesity combinations. With semaglutide 2.4 mg, it produced 22.1% weight loss at 72 weeks, mostly as fat, with lean mass largely preserved.
- More muscle has not meant better function. Trials in sarcopenia, hip fracture, COPD and inclusion body myositis all failed their functional endpoints.
- Notable side effects. Muscle spasms, diarrhea and acne were common, LDL cholesterol rose, and up to about one in five people on bimagrumab alone stopped early.
- Unapproved and banned in sport. It is investigational only (Lilly, phase 2) and is named explicitly on the WADA list.
Sources
- Lach-Trifilieff E, Minetti GC, Sheppard K, et al. An antibody blocking activin type II receptors induces strong skeletal muscle hypertrophy and protects from atrophy. Mol Cell Biol. 2014;34(4):606–618. PubMed.
- Heymsfield SB, Aronne LJ, Montgomery P, et al. Bimagrumab plus semaglutide alone or in combination for the treatment of obesity: a randomized phase 2 trial. Nat Med. 2026;32(3):869–882. PubMed.
- Heymsfield SB, Coleman LA, Miller R, et al. Effect of bimagrumab vs placebo on body fat mass among adults with type 2 diabetes and obesity: a phase 2 randomized clinical trial. JAMA Netw Open. 2021;4(1):e2033457. PubMed.
- Shao C, Lin H, Yu J, et al. Efficacy and safety of bimagrumab in adults with obesity and metabolic dysfunction: a systematic review and meta-analysis of randomized controlled trials. Diabetes Obes Metab. 2026;28(10):9433–9442. PubMed.
- Rooks D, Petricoul O, Praestgaard J, et al. Safety and pharmacokinetics of bimagrumab in healthy older and obese adults with body composition changes in the older cohort. J Cachexia Sarcopenia Muscle. 2020;11(6):1525–1534. PubMed.
- Petricoul O, Nazarian A, Schuehly U, et al. Pharmacokinetics and pharmacodynamics of bimagrumab (BYM338). Clin Pharmacokinet. 2023;62(1):141–155. PubMed.
- Rooks D, Praestgaard J, Hariry S, et al. Treatment of sarcopenia with bimagrumab: results from a phase II, randomized, controlled, proof-of-concept study. J Am Geriatr Soc. 2017;65(9):1988–1995. PubMed.
- Rooks D, Swan T, Goswami B, et al. Bimagrumab vs optimized standard of care for treatment of sarcopenia in community-dwelling older adults: a randomized clinical trial. JAMA Netw Open. 2020;3(10):e2020836. PubMed.
- Hofbauer LC, Witvrouw R, Varga Z, et al. Bimagrumab to improve recovery after hip fracture in older adults: a multicentre, double-blind, randomised, parallel-group, placebo-controlled, phase 2a/b trial. Lancet Healthy Longev. 2021;2(5):e263–e274. PubMed.
- Polkey MI, Praestgaard J, Berwick A, et al. Activin type II receptor blockade for treatment of muscle depletion in chronic obstructive pulmonary disease. A randomized trial. Am J Respir Crit Care Med. 2019;199(3):313–320. PubMed.
- Hanna MG, Badrising UA, Benveniste O, et al. Safety and efficacy of intravenous bimagrumab in inclusion body myositis (RESILIENT): a randomised, double-blind, placebo-controlled phase 2b trial. Lancet Neurol. 2019;18(9):834–844. PubMed.
- Amato AA, Hanna MG, Machado PM, et al. Efficacy and safety of bimagrumab in sporadic inclusion body myositis: long-term extension of RESILIENT. Neurology. 2021;96(12):e1595–e1607. PubMed.
- Rooks DS, Laurent D, Praestgaard J, et al. Effect of bimagrumab on thigh muscle volume and composition in men with casting-induced atrophy. J Cachexia Sarcopenia Muscle. 2017;8(5):727–734. PubMed.
- Garito T, Zakaria M, Papanicolaou DA, et al. Effects of bimagrumab, an activin receptor type II inhibitor, on pituitary neurohormonal axes. Clin Endocrinol (Oxf). 2018;88(6):908–919. PubMed.
- Rooks D, Yates DP, Neelakantham S, et al. Cardiac safety of chronic inhibition of the myostatin-activin pathway with bimagrumab in healthy older adults. J Clin Endocrinol Metab. 2026;111(9):2573–2582. PubMed.
- Nunn E, Jaiswal N, Gavin M, et al. Antibody blockade of activin type II receptors preserves skeletal muscle mass and enhances fat loss during GLP-1 receptor agonism. Mol Metab. 2024;80:101880. PubMed.
- Carlsson M, Frank E, Màrmol JM, et al. Activin receptor type IIA/IIB blockade increases muscle mass and strength, but compromises glycemic control in mice. Mol Metab. 2025;102:102261. PubMed.
- Eli Lilly and Company, Versanis Bio. Lilly to acquire Versanis to improve patient outcomes in cardiometabolic diseases. Press release, July 14, 2023. BioSpace.
- ClinicalTrials.gov. Bimagrumab studies: all registered studies; NCT06643728 (bimagrumab and tirzepatide, phase 2); NCT06901349 (phase 2b, withdrawn).
- World Anti-Doping Agency. The 2026 Prohibited List, class S4.3. WADA 2026 Prohibited List.
- Schedules of controlled substances: Schedule III. 21 CFR 1308.13. eCFR.