Pharmacological intervention: Challenges and promising outcomes for fat loss and preservation of lean body mass in the treatment of overweight and type 2 diabetes.
Level 5 - mechanism / opinion, no new human data
Narrative review synthesizing preclinical and early-phase clinical studies without systematic meta-analysis.
PubMed 41178728 · doi:10.1111/dom.70229
What was done
The authors conducted a literature review across PubMed, JAMA, Wiley, ResearchGate, The Royal Danish Library, and ClinicalTrials.gov. They examined preclinical and clinical studies of anabolic pharmacological agents to assess their ability to preserve or increase lean body mass and reduce fat mass during weight loss, particularly in the context of GLP-1 receptor agonist treatment in individuals with overweight and type 2 diabetes. Assessed outcomes included lean body mass, fat mass, physical function, and adverse events.
What was found
The abstract reports no numerical findings, effect sizes, or study counts. Qualitatively, activin II receptor inhibition with bimagrumab demonstrated lean body mass preservation and increases alongside fat mass reduction in preclinical and phase 2 studies. Similar qualitative effects were reported for myostatin and activin A inhibitors (trevogrumab, garetosmab), latent myostatin inhibitors (apitegromab, SRK-439), and the selective androgen receptor modulator enobosarm, which was also reported to improve physical function. Adverse events were noted to be generally mild and reversible.
Why it matters
Weight loss induced by GLP-1 receptor agonists often includes a substantial loss of fat-free mass and skeletal muscle. This review outlines emerging pharmacological candidates that could be co-administered to preserve muscle mass and physical function during weight loss.
Limits
The review relies on preclinical and early-phase (phase 2) studies, and long-term safety and efficacy data remain limited. The abstract does not provide quantitative data, total participant counts, or systematic risk-of-bias grading.
Cited by
- supports Roledumab and trevogrumab are monoclonal antibody myostatin inhibitors designed to maintain muscle mass in a caloric deficit.