Evidence map›Paper›PMID 40360507›Full record

ArticleNature communications2025

GDF8 and activin A blockade protects against GLP-1-induced muscle loss while enhancing fat loss in obese male mice and non-human primates.

Jason W Mastaitis, Daniel Gomez, José G Raya, Diana Li, Soo Min, Michael Stec, Sandra Kleiner, Toya McWilliams, Judith Y Altarejos, Andrew J Murphy and 2 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

37 citing papers in PubMed.

  1. Trial
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  7. Article
  8. The evolving landscape of obesity pharmacotherapy.Nature reviews. Drug discovery · 2026
    Review
  9. Review
  10. Review
  11. Review
  12. Article
  13. 15-PGDH inhibition promotes muscle repair and strength recovery during GLP-1 receptor agonist-induced weight loss.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  14. Review
  15. Review
  16. Exercise pills for cardiometabolic health cannot mimic the exercise milieu.Trends in endocrinology and metabolism: TEM · 2026
    Review
  17. Article
  18. Article
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Jason W MastaitisRegeneron Pharmaceuticals, Tarrytown, NY, USA.ORCID http://orcid.org/0000-0002-9991-3509
Daniel GomezRegeneron Pharmaceuticals, Tarrytown, NY, USA.
José G RayaRegeneron Pharmaceuticals, Tarrytown, NY, USA.
Diana LiRegeneron Pharmaceuticals, Tarrytown, NY, USA.
Soo MinRegeneron Pharmaceuticals, Tarrytown, NY, USA.
Michael StecRegeneron Pharmaceuticals, Tarrytown, NY, USA.
Sandra KleinerRegeneron Pharmaceuticals, Tarrytown, NY, USA.
Toya McWilliamsRegeneron Pharmaceuticals, Tarrytown, NY, USA.
Judith Y AltarejosRegeneron Pharmaceuticals, Tarrytown, NY, USA.ORCID http://orcid.org/0000-0003-2764-6074
Andrew J MurphyRegeneron Pharmaceuticals, Tarrytown, NY, USA.ORCID http://orcid.org/0000-0003-4152-4081
George D YancopoulosRegeneron Pharmaceuticals, Tarrytown, NY, USA.
Mark W SleemanRegeneron Pharmaceuticals, Tarrytown, NY, USA. Mark.Sleeman@regeneron.com.ORCID http://orcid.org/0000-0002-3329-0919

Funding

Regeneron Pharmaceuticals (Regeneron Pharmaceuticals, Inc.) N/A
6 · The paper itself

Abstract

Glucagon-like peptide-1 receptor agonists act via appetite suppression and caloric restriction. These treatments can result in significant muscle loss, likely due to evolutionary mechanisms protecting against food scarcity as muscle is a major energy utilizer. One mechanism that reduces muscle mass involves activation of type II activin receptors, ActRIIA/B, which yield profound muscle growth in humans when blocked. We previously demonstrated GDF8, also known as myostatin, and activin A are the two major ActRIIA/B ligands mediating muscle minimization. Here, we report that dual blockade can also prevent muscle loss associated with glucagon-like peptide-1 receptor agonists - and even increase muscle mass - in both obese mice and non-human primates; moreover, this muscle preservation enhances fat loss and is metabolically beneficial. These data raise the possibility that supplementing glucagon-like peptide-1 receptor agonist treatment with GDF8 and activin A blockade could greatly improve the quality of weight loss during the treatment of obesity in humans.

Indexed as

ActivinsGlucagon-Like Peptide 1MyostatinObesityActivin Receptors, Type IIAdipose TissueAnimalsGlucagon-Like Peptide-1 ReceptorGlucagon-Like Peptide-1 Receptor AgonistsHumansMaleMiceMice, Inbred C57BLMice, ObeseMuscle, Skeletalactivin AActivin Receptors, Type IIactivin receptor type II-BActivinsGlucagon-Like Peptide 1Glucagon-Like Peptide-1 ReceptorGlucagon-Like Peptide-1 Receptor AgonistsMstn protein, mouseMyostatin

Identifiers

PMID40360507
PMCPMC12075787

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.