Recent research published in the journal GeroScience explores the effects of GLP-1 (glucagon-like peptide-1) and GIP (gastric inhibitory polypeptide) receptor agonism on skeletal muscle atrophy and myogenesis in primary human myotubes. This study is particularly relevant given the increasing use of incretin-based therapies in older adults, who are at risk of sarcopenia.
The study involved isolating primary myoblasts from the skeletal muscle of older adults with obesity undergoing orthopedic surgery. Researchers characterized the expression of GIPR (GIP receptor) and GLP-1R (GLP-1 receptor) using RT-qPCR and flow cytometry. The differentiated myotubes were then treated with semaglutide (a GLP-1 receptor agonist) or GIP peptide, followed by assessments of atrophy-related gene expression, secretome perturbation, mitochondrial and glycolytic bioenergetics, and myotube morphology.
Findings revealed that GIPR mRNA was consistently detected across all donors, while GLP-1R mRNA was undetectable by PCR. However, flow cytometry identified low-level surface GLP-1R protein in a subset of donors. Importantly, neither semaglutide nor GIP treatment altered atrophy-related gene expression or the secretome, with no significant changes in protein levels observed.
Interestingly, semaglutide was found to reduce glycolytic and total ATP production rates, accompanied by decreased lactate secretion, indicating a modest suppression of glycolytic flux. However, mitochondrial parameters remained unaffected. Furthermore, neither treatment impaired myotube thickness or differentiation; in fact, GIP treatment increased myotube thickness after eight days.
Overall, the study concludes that direct activation of GLP-1 and GIP receptors does not produce significant atrophic, inflammatory, morphological, myogenic, or mitochondrial effects on primary human skeletal muscle myotubes. These results suggest that the lean mass loss observed with incretin-based therapies may be due to indirect mechanisms rather than direct pharmacological effects on skeletal muscle.
What this study does not show
This study does not establish a causal relationship between GLP-1 and GIP receptor agonism and muscle atrophy or myogenesis in humans, nor does it address the long-term effects of these treatments on muscle health.
Evidence scorecard
- Analytic validity: Established
- Clinical validity: Not established
- Clinical utility: Not established
The evidence is based on primary research involving human myotubes.