Investigating the Interplay between GLP-1 Receptor Agonists and Skeletal Muscle Health

The field of metabolic disease therapeutics has experienced rapid advancement with the introduction of glucagon-like peptide-1 receptor agonists (GLP-1RAs), now a cornerstone in the management of obesity and type 2 diabetes. Despite their well-documented efficacy in glycemic control and weight reduction, recent clinical evidence indicates an unexpected and pressing concern: the impact of GLP-1RA therapy on skeletal muscle health. Reports of sarcopenia emerging as a side effect in populations treated with GLP-1RAs, particularly among the elderly and non-obese individuals, have ignited an urgent discourse within the endocrinology and geriatric medicine communities. While the primary focus of GLP-1RA research has centered on cardiovascular and metabolic outcomes, muscular adverse effects and the underlying biological mechanisms remain inadequately characterized. This gap has made it crucial to further investigate how GLP-1RAs influence muscle mass, function, and structural integrity, especially as their use broadens across diverse patient populations.Recent studies have begun to unravel the molecular and physiological pathways affected by GLP-1 receptor activation in skeletal muscle, highlighting changes in protein turnover, mitochondrial function, and possible inflammatory processes. However, results remain contradictory, with some findings suggesting protective effects, while others demonstrate exacerbated muscle loss and compromised function. These discrepancies may be attributed to patient heterogeneity, variations in drug formulation or dosing, and insufficient stratification based on age, comorbidities, or baseline muscle health. Furthermore, research has only just begun to assess the long-term outcomes and the potential for targeting specific components of signaling cascades to prevent or reverse sarcopenic changes in this context. Exploratory screening for novel pharmacological targets, as well as unbiased clinical investigations, are warranted to address these unresolved questions and to optimize therapeutic strategies.This Research Topic aims to comprehensively elucidate the molecular, structural, and clinical consequences of GLP-1RA treatment for skeletal muscle health, with a focus on emerging evidence and knowledge gaps regarding sarcopenia. We seek to bring together mechanistic studies, clinical data, and drug discovery reports to advance our understanding of the dualistic effects of GLP-1RAs and to inform clinical practice, particularly for vulnerable patient groups. Contributions that address the effect of patient phenotypes, drug dosing, novel molecular targets, or unbiased clinical outcomes across age groups are especially encouraged to foster a robust dialogue and support future translational efforts.To gather further insights into the intersection of GLP-1RA pharmacology and skeletal muscle biology, with an emphasis on translational and integrative research, we welcome original research, review, and perspective articles addressing, but not limited to, the following themes:- Mechanistic pathways by which GLP-1RAs modulate skeletal muscle metabolism and structure- Structural and functional assessments of muscle in GLP-1RA-treated populations- Unbiased screening platforms to identify novel druggable targets for muscle protection- Clinical evidence and real-world outcomes of GLP-1RA use in elderly, non-obese, or multimorbid patients- Interactions between GLP-1RA therapy and physical activity or nutritional interventions- Longitudinal studies on the risk, onset, and reversibility of GLP-1RA-induced sarcopenia- Strategies to personalize GLP-1RA therapy and mitigate adverse muscular effectsJoe Brozinick is an employee of Eli Lilly and Company. Topic editors: Joe Brozinick, Patrick T. Fueger, Ke Ma Source: https://www.frontiersin.org/research-topics/77278/investigating-the-interplay-between-glp-1-receptor-agonists-and-skeletal-muscle-health