The Short Answer
Weight loss on GLP-1 drugs includes some lean mass as well as fat. Two drugs that target the myostatin/activin pathway, a natural brake on muscle growth, are being tested to change that ratio:
- Bimagrumab (Eli Lilly) blocks activin type II receptors (ActRIIA and ActRIIB). It is investigational and not approved anywhere we found.
- Apitegromab (Scholar Rock) binds the inactive precursor forms of myostatin so it can't be activated. It is FDA-approved as ISEMBYLD, but only for spinal muscular atrophy (SMA). Its obesity use is still investigational.
Neither is a peptide. Both are fully human monoclonal antibodies, large proteins made in cell culture and given by intravenous (IV) infusion in trials. They can't be compounded and aren't "research peptides." Claims of "muscle gain in a pill" for either drug are wrong. Neither has been studied as a pill, and the goal in the obesity trials was preserving lean mass during weight loss, not building muscle.
This page summarizes published and sponsor-reported trial data. It isn't dosing guidance.
Why the Myostatin Pathway
Myostatin and activin A signal through activin type II receptors to limit muscle growth. Blocking that pathway increases muscle mass in animals and people. The obesity question is whether blocking it during GLP-1 weight loss can tilt losses toward fat.
PeptIQ has covered this pathway in the research wiki, including a 2022 review of myostatin-inhibiting strategies. Peptide-based ideas such as follistatin-344 and ACE-031 have much weaker human evidence than the two antibodies here.
Bimagrumab: What the Trials Show
BELIEVE: bimagrumab with semaglutide (Nature Medicine, March 2026)
BELIEVE (NCT05616013) was a Lilly-funded, placebo-controlled phase 2 trial. Bimagrumab was double-blind; semaglutide was given open-label.
- 507 adults with obesity (BMI ≥30, or ≥27 with a weight-related condition), without diabetes.
- Nine groups for 48 weeks: placebo, bimagrumab alone (two IV doses), semaglutide alone (two doses) and four combinations. An open-label extension ran to week 72.
- Primary endpoint: change in body weight at week 48.
Weight, week 48 (least-squares mean):
| Group | Body weight change | % change range across doses |
|---|---|---|
| Placebo | -3.3 kg | -3.5% |
| Bimagrumab alone (high dose) | -9.3 kg | -5.6% to -8.6% |
| Semaglutide 2.4 mg alone | -14.2 kg | -9.8% to -13.5% |
| High-dose combination | -17.8 kg | -12.0% to -16.4% |
The high-dose combination lost more weight than semaglutide 2.4 mg alone (P < 0.05).
Body composition, week 48 (DXA scan):
- Total lean mass changed by +1.0% to +1.1% with bimagrumab alone, -4.7% to -6.9% with semaglutide alone, and -0.8% to -2.3% with the combinations, versus -0.9% with placebo.
- Share of weight lost that was fat ("fat loss index"): 100% with high-dose bimagrumab alone, 71.1% with semaglutide 2.4 mg, and 92.3% with the high-dose combination.
- Visceral fat fell 41.0% to 54.8% with the combinations.
- At week 72 the pattern held: fat accounted for 92.2% of weight lost with the high-dose combination versus 75.6% with semaglutide 2.4 mg.
Safety and tolerability:
- Common adverse events with bimagrumab were muscle spasms (mostly cramps), diarrhea and acne. Semaglutide brought its usual nausea, diarrhea, constipation and fatigue.
- Discontinuations due to adverse events were 14.0% to 21.4% in the bimagrumab-alone groups, versus 3.6% to 8.8% with semaglutide, 5.3% to 12.5% with the combinations, and 3.6% with placebo.
Earlier: bimagrumab in type 2 diabetes (JAMA Network Open, 2021)
A 48-week phase 2 trial randomized 75 adults with type 2 diabetes and overweight or obesity to IV bimagrumab or placebo. Bimagrumab changed fat mass by -20.5% versus -0.5%, lean mass by +3.6% versus -0.8%, and HbA1c by -0.76 points versus -0.04. Only participants who completed treatment were analysed, and 58 of 75 finished.
A 2026 meta-analysis of four randomized trials (268 participants) found bimagrumab reduced weight and fat and increased lean mass versus placebo. It also linked bimagrumab to higher LDL cholesterol, more discontinuations, muscle spasms and diarrhea.
What's next for bimagrumab
ClinicalTrials.gov lists a Lilly phase 2 of bimagrumab with tirzepatide (NCT06643728, active, not recruiting), an academic phase 2 at Massachusetts General Hospital (NCT05933499), and a new Lilly phase 2 in heart failure with preserved ejection fraction (NCT07920887, not yet recruiting). We found no registered phase 3 in obesity.
Apitegromab: What the Trials Show
Approved use: spinal muscular atrophy
FDA approved apitegromab as ISEMBYLD (BLA 761463) for SMA in patients 2 years and older who are already receiving an SMN2-targeted treatment (nusinersen or risdiplam, for example). The label lists initial US approval in 2026. DailyMed shows a September 2026 label.
The approval rests on SAPPHIRE (NCT05156320), a phase 3 trial of 188 nonambulatory patients aged 2 to 21, published in Lancet Neurology (2025). In the main 2–12-year-old group, motor function on the HFMSE scale improved by 1.8 points more than placebo for both doses combined (p = 0.019). The higher dose alone did not reach statistical significance versus placebo (1.4 points, p = 0.11). The FDA label reports its own analysis and calls the result "nominally" statistically significant.
