Myostatin Inhibitors and GLP-1 Drugs: A Claim-by-Claim Check

On 2026-11-06 the X account @maxmarchione posted an article titled “Myostatin inhibitors will be the next GLP-1”. It mixes real genetics, two real phase 2 trials and one real FDA approval with several statements that are wrong, misattributed or unsourced. This page tests each checkable claim. A post is a claim, not evidence, so each row below gets a verdict.

Key points

• Myostatin is a real brake on muscle growth in mice, cattle and dogs, and one human child with two inactive copies was documented in 2004 [1][2][6].
• In the BELIEVE trial the +2.5% lean mass figure belongs to bimagrumab alone, not the combination. With semaglutide the lean mass change was -2.9%, against -7.4% for semaglutide alone [14].
• The FDA approved apitegromab (ISEMBYLD) on 2026-09-11 for spinal muscular atrophy, not obesity [21][22].
• Both obesity trials measured lean mass by DXA, were short and company-funded, and did not show better strength or function [14][18].
• Myostatin-pathway drugs are investigational for obesity. Long-term safety in people on GLP-1 drugs is unknown.

Claim check: the genetics

Claim in the article	Verdict	What the sources show
Myostatin-knockout mice have about 2x the muscle (Lee, 1997)	Supported	Individual muscles of GDF-8 null mice weighed 2-3 times more than normal, through more and larger fibres [1].
Belgian Blue and Piedmontese cattle carry MSTN mutations	Supported	McPherron and Lee (PNAS, 1997) found an 11-nucleotide deletion in Belgian Blue and a missense change in Piedmontese [2]. Grobet et al. (Nature Genetics, 1997) independently found the deletion; double-muscled cattle carry roughly 20% more muscle [3]. Caesarean calving and costly diets: could not verify in the papers we opened.
Bully whippets are slower; the fastest racers carry one broken copy	Partly supported	Mosher et al. (PLoS Genetics, 2007): bully whippets carry two copies of a 2-base deletion; one copy meant more muscle and faster racing [4]. The abstract does not test “slower than siblings”.
Sprinting Thoroughbreds carry one broken copy	Not supported as worded	Hill et al. (PLoS ONE, 2010; 148 horses) tied a sequence variant to best race distance: C/C to short races, C/T to middle, T/T to stamina. No “broken copy” is described [5].
A German boy (2004) has the mutation	Supported	NEJM, June 2004, one child: muscles about twice the usual size on ultrasound, two copies of the mutation, no myostatin detectable in blood. His mother, a former professional athlete, carries one copy. The authors could not say what happens as he ages [6].
Liam Hoekstra: iron cross at 5 months, 40% more muscle, same mutation	Could not verify	ABC News/AP (2009) quotes his mother on the iron cross and reports a diagnosis of “myostatin-related muscle hypertrophy”, but no genetic result and no 40% figure [7]. We found no peer-reviewed case report.
Eddie Hall carries the “Hercules gene”; adopted mother, Scandinavian ancestry	Could not verify	Hall posted about a consumer DNA test (Muhdo) in 2025; coverage cites no lab report or paper [8]. We found the adoption and ancestry story in no source we opened. “Hercules gene” is a media nickname.
One mutated copy gives people an athletic edge; deficient people have less fat, stronger grip, healthy hearts and fertility	Not supported in humans	The edge is shown in dogs [4]. A 2022 meta-analysis of the K153R variant (4 studies, 416 athletes, 357 controls) found OR 2.02, P = 0.05, and called for more work [9]. Grip, fat and fertility were not reported for the one documented child [6].
Myostatin is “likely a famine adaptation”	Hypothesis, not established	Related thrifty-genotype ideas still have “main predictions” that “remain untested” [10]. We found no study testing this for myostatin.

Claim check: GLP-1 drugs, trials and the approval

Claim in the article	Verdict	What the sources show
Up to 40% of GLP-1 weight loss can be lean mass	Partly supported	A 2024 expert commentary gives 25-39% [11]. The SURMOUNT-1 tirzepatide DXA substudy (160 people) found about 25% [13]. The STEP 1 DXA substudy (140 people) reported total lean mass down 9.7% on semaglutide [12]. BELIEVE’s authors write “25-40%” [14]. 40% is the top of the range.
In BELIEVE, 507 people took semaglutide with bimagrumab	Misleading	507 were randomised to nine groups. The four combination groups total 225 people; 57 were in the highest combination group [14][16].
22.1% vs 15.7% weight loss at 72 weeks	Supported, with caveats	Highest combination vs semaglutide alone [14]. The primary endpoint was week 48 (-17.8 vs -14.2 kg). The authors call all week 72 analyses post hoc, made no multiplicity adjustment, and warn against inferring definitive effects [14].
92% of the loss was fat	Supported	92.2% vs 75.6% for semaglutide alone at week 72 [14]. The Pennington release says 92.8% [15].
Bimagrumab raised lean mass 2.5% vs a 7.4% cut with semaglutide	Misattributed	+2.5% is bimagrumab alone; -7.4% is semaglutide alone; the combination was -2.9% [14].
FDA approved apitegromab as ISEMBYLD for SMA, ages 2+	Supported, condition omitted	The FDA page (current as of 2026-09-11) covers adults and children 2 and older who are already on an SMN2-targeted treatment [21]. Scholar Rock announced it the same day [22].
“First myostatin inhibitor”	Company framing	The FDA calls it the first SMA therapy to target muscle loss directly and does not mention myostatin [21]. In August 2026 the CEO called a first myostatin-inhibitor approval a prospect [23].
102 adults on tirzepatide, apitegromab or placebo; 1.6 vs 3.5 kg lean mass at 24 weeks	Supported, with caveats	EMBRAZE randomised 102 (51 per arm); the figures come from 43 and 44 completers with a week 24 DXA scan. Weight loss was similar. The authors set a 0.20 significance level with 80% intervals and no multiplicity adjustment [18][19][20].

What BELIEVE and EMBRAZE are

BELIEVE (NCT05616013) was a Lilly-sponsored phase 2 trial in adults with obesity, excluding diabetes. It ran 48 weeks blinded to bimagrumab, then a 24-week open-label extension. Semaglutide itself was open-label. It appeared in Nature Medicine on 2026-03-02 [14][16]. Bimagrumab blocks activin type II receptors, so it affects myostatin and activin A signalling rather than myostatin alone [14].

EMBRAZE (NCT06445075) was a Scholar Rock-funded phase 2 proof-of-concept study. Participants were 18-65, without diabetes. It appeared in Nature Medicine on 2026-06-08 [18][20]. Apitegromab selectively blocks myostatin activation [18].

Both are company-funded and short. Neither is a phase 3 trial.

How lean mass is measured

All the lean mass numbers above come from DXA, which splits the body into fat, lean tissue and bone. “Lean mass” is not muscle: it includes water and organs, and the EMBRAZE authors note that DXA cannot cleanly separate compartments and that hydration affects accuracy [18]. The SURMOUNT-1 authors note that a four-compartment model may be more accurate [13]. The BELIEVE authors say earlier bimagrumab studies used MRI and that future work should too [14]. The 25-40% range also varies by trial, drug, duration and sub-sample.

For the broader evidence on muscle and incretin drugs, see GLP-1 weight loss and lean mass: what the evidence shows. For bimagrumab’s owner, see the Eli Lilly GLP-1 business overview. Lilly’s own listing for the bimagrumab-tirzepatide phase 2 study (NCT06643728, 252 participants) shows primary completion on 2026-01-16 and no posted results [17].

Regulatory status

• Apitegromab (ISEMBYLD): FDA-approved on 2026-09-11 for SMA in adults and children 2 and older on an SMN2-targeted treatment [21][22]. Not approved for obesity. In the EU it is not approved; Scholar Rock resubmitted its marketing application to the EMA on 2026-10-08 and expects a CHMP opinion in the first half of 2027 [24]. We did not find UK (MHRA) status.
• Bimagrumab: described in the Nature Medicine paper as investigational [14]. We found no approval anywhere.
• Semaglutide and tirzepatide: The FDA approved tirzepatide (Zepbound) for chronic weight management on 2023-11-08 [25]; the BELIEVE paper describes semaglutide at its obesity-treatment dose as approved for obesity [14]. We did not check EMA, MHRA or BfArM status here.
• Trevogrumab, taldefgrobep alfa, SRK-439: named in the article. We did not verify their status.
• “Research use only” does not apply to any of these; all are drugs developed by pharmaceutical companies.

Risks and unknowns

• Bone and fractures: In SAPPHIRE (SMA, ages 2-21), fractures occurred in 9% on the recommended arm vs 2% on placebo, per the company release; the FDA lists fractures and potential fetal harm as warnings [21][22]. Whether this applies to adults with obesity is unknown.
• Bimagrumab tolerability: In BELIEVE, discontinuations for adverse events through week 48 were 14.0-21.4% in bimagrumab groups, 5.3-12.5% in combination groups, 3.6% on placebo. Muscle spasms, diarrhoea and acne were common; creatine kinase, ALP and ALT rose [14].
• Function: BELIEVE found no significant improvement in grip strength or patient-reported outcomes [14]. In EMBRAZE, exploratory handheld-force and chair-stand measures showed no notable differences [18]. Whether extra DXA lean mass means better function is unproven.
• Duration and populations: 24 and 72 weeks; people with diabetes excluded in both; EMBRAZE mostly women [14][18].
• Long-term safety: the one documented person with no myostatin was followed only briefly, and the authors said later problems could not be ruled out [6].
• Combinations: the FDA approval covers SMA only. Combining a myostatin-pathway drug with a GLP-1 drug is not an approved use.

Frequently asked questions

Is there an approved myostatin inhibitor? Yes, one, for a different disease. The FDA approved apitegromab (ISEMBYLD) on 2026-09-11 for spinal muscular atrophy in people 2 and older already on an SMN2-targeted treatment [21]. It is not approved for obesity or muscle loss on GLP-1 drugs.

Did bimagrumab with semaglutide build muscle in BELIEVE? No. Bimagrumab alone raised DXA lean mass by 2.5% at week 72. With semaglutide, lean mass fell 2.9%, against 7.4% for semaglutide alone [14].

Does 40% of GLP-1 weight loss come from muscle? No. It is lean mass, measured by DXA, and 40% is the top of a 25-40% range. Trials report about a quarter to two-fifths [11][13][14].

Is Eddie Hall’s “Hercules gene” documented? Only through his own social posts and a consumer DNA test; we found no lab report or paper [8].

Sources

1. McPherron AC, Lawler AM, Lee SJ, Nature, “Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member” (1997-05). https://europepmc.org/article/MED/9139826
2. McPherron AC, Lee SJ, PNAS, “Double muscling in cattle due to mutations in the myostatin gene” (1997-11). https://europepmc.org/article/MED/9356471
3. Grobet L et al., Nature Genetics, “A deletion in the bovine myostatin gene causes the double-muscled phenotype in cattle” (1997). https://agris.fao.org/search/zh/records/674851027625988a371a36a3
4. Mosher DS et al., PLoS Genetics, “A mutation in the myostatin gene increases muscle mass and enhances racing performance in heterozygote dogs” (2007-04-30). https://europepmc.org/article/MED/17530926
5. Hill EW et al., PLoS ONE, “A sequence polymorphism in MSTN predicts sprinting ability and racing stamina in thoroughbred horses” (2010-01-20). https://europepmc.org/article/MED/20098749
6. ScienceDaily, report on Schuelke et al., NEJM, “Myostatin mutation associated with gross muscle hypertrophy in a child” (2004-06-24). https://sciencedaily.com/releases/2004/06/040624094836.htm
7. ABC News, “Super Strong Kids May Hold Genetic Secrets” (2009-04-01). https://abcnews.com/Health/MedicineCuttingEdge/story?id=7231487
8. Sport Manual, “Eddie Hall Reveals He Has DNA Gene Mutation That Results In His Huge Size And Strength” (2025-09-15). https://sportmanual.co.uk/2025/09/15/eddie-hall-reveals-he-has-dna-gene-mutation-that-results-in-his-huge-size-and-strength/
9. Genes, “Association of Myostatin Gene Polymorphisms with Strength and Muscle Mass in Athletes: A Systematic Review and Meta-Analysis of the MSTN rs1805086 Mutation” (2022). https://pmc.ncbi.nlm.nih.gov/articles/PMC9690375/
10. Vanderbilt University, “Beyond the thrifty genotype: examining evolutionary hypotheses for modern metabolic health” (2024-11-12). https://www.vanderbilt.edu/evolution/beyond-the-thrifty-genotype-examining-evolutionary-hypotheses-for-modern-metabolic-health/
11. EurekAlert, news release on the Prado, Phillips, Gonzalez and Heymsfield commentary “Muscle Matters” (2024-10-25). https://www.eurekalert.org/news-releases/1062733
12. Wilding JPH et al., J Endocr Soc, “Impact of semaglutide on body composition in adults with overweight or obesity: exploratory analysis of the STEP 1 study” (conference abstract, 2021-05). https://pmc.ncbi.nlm.nih.gov/articles/PMC8089287
13. Look M et al., Diabetes Obes Metab, “Body composition changes during weight reduction with tirzepatide in the SURMOUNT-1 study” (2025-02-25). https://pmc.ncbi.nlm.nih.gov/articles/PMC11965027/
14. Heymsfield SB et al., Nature Medicine, “Bimagrumab plus semaglutide alone or in combination for the treatment of obesity: a randomized phase 2 trial” (2026-03-02). https://pmc.ncbi.nlm.nih.gov/articles/PMC13004672/
15. Pennington Biomedical Research Center, “Combination GLP-1 therapy shows fat mass loss while preserving lean mass in adults with obesity” (2026-03-05). https://www.pbrc.edu/news/media/2026/semaglutide_and_bimagrumab.aspx
16. ClinicalTrials.gov, NCT05616013, bimagrumab and semaglutide in adults with overweight or obesity (Eli Lilly; 507 enrolled; completed). https://clinicaltrials.gov/study/NCT05616013
17. ClinicalTrials.gov, NCT06643728, bimagrumab and tirzepatide (Eli Lilly; 252 enrolled; primary completion 2026-01-16). https://clinicaltrials.gov/study/NCT06643728
18. Nature Medicine, “Apitegromab for lean mass preservation during tirzepatide-induced weight loss: a randomized, double-blind, placebo-controlled phase 2 trial” (2026-06-08). https://pmc.ncbi.nlm.nih.gov/articles/PMC13375528/
19. Scholar Rock, EMBRAZE topline press release (2025-06-18). https://www.sec.gov/Archives/edgar/data/1727196/000155837025008711/srrk-20250618xex99d1.htm
20. ClinicalTrials.gov, NCT06445075, apitegromab in adults who are overweight or obese (Scholar Rock; 102 enrolled). https://clinicaltrials.gov/study/NCT06445075
21. FDA, “FDA Approves First Therapy to Target Muscle Loss in Spinal Muscular Atrophy” (content current 2026-09-11). https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-first-therapy-target-muscle-loss-spinal-muscular-atrophy
22. Scholar Rock, “Scholar Rock Announces FDA Approval of ISEMBYLD (apitegromab-mstn)” (2026-09-11; read via a Finviz copy of the Business Wire text). https://finviz.com/news/391334/scholar-rock-announces-fda-approval-of-isembyld-apitegromab-mstn-the-first-and-only-muscle-targeted-treatment-for-children-and-adults-with-spinal-muscular-atrophy-sma
23. Scholar Rock, second quarter 2026 results, Form 8-K Exhibit 99.1 (2026-08-06). https://www.sec.gov/Archives/edgar/data/0001727196/000119312526336715/srrk-ex99_1.htm
24. Scholar Rock, MAA resubmission to the EMA (2026-10-08; read via a Finviz copy). https://finviz.com/news/400325/scholar-rock-resubmits-apitegromab-marketing-authorisation-application-maa-to-european-medicines-agency-ema-for-treatment-of-children-and-adults-with-spinal-muscular-atrophy-sma
25. FDA, “FDA Approves New Medication for Chronic Weight Management” (2023-11-08). https://www.fda.gov/news-events/press-announcements/fda-approves-new-medication-chronic-weight-management

This article is information, not medical advice.