Table 2. Summary and Analysis of Supporting Studies Related to Semaglutide-Induced Sarcopenia and Hyperglycemia

Study / Source	Design & Population	Key Findings (Quantitative Estimates)	Mechanistic / Hypothetical Linkage
Semaglutide Therapy and Accelerated Sarcopenia [26]	Retrospective cohort (n=432, older adults with T2DM)	↓ ASMI (7–12%),↓ grip strength (12–18%),↓ gait speed (0.15–0.25 m/s); sarcopenia prevalence 27.7%;dosage significant predictor	Suggests GLP-1R–mTOR suppression, impaired satellite cell proliferation, initiating muscle–glucose feedback loop with hyperglucagonemia (~20% rise).
Neuromuscular Junction Degradation [27]	Longitudinal cohort(n=141, older men with T2DM)	↓ HGS (15–25%),↓ ASMI (6–10%),↓ SPPB scores;↑ CAF22/NfL (20–30%)	Indicates NMJ disassembly and neuronal injury, exacerbating disuse atrophy and reducing GLUT4 translocation (~25%).
SLIM LIVER Analysis [28]	Secondary study(n=51, MASLD patients, 24 weeks)	↓ Psoas muscle volume (9.3%);no significant functional change	Consistent with AMPK-driven mitochondrial loss,↓ ATP production (~30%), early sarcopenic trajectory.
Case Report: Sarcopenia & Fatigue [29]	74-year-old male, T2DM	8 kg weight loss,↓ muscle strength (25%);improved with dose reduction + resistance training	Linked to myokine reprogramming (↑ GDF15 by ~20%), suggesting partial reversibility.
Case Report: Rhabdomyolysis [30]	47-year-old female	Myalgias, weakness, ↑ CK;resolved after discontinuation, recurred on rechallenge	Represents acute FOXO/ubiquitin activation, paralleling chronic sarcopenia mechanisms.
GLP-1 and Sarcopenia (Clinical/Experimental)[31]	Mixed clinical + in vitro (n=145)	↑ GLP-1 in sarcopenia(1021 vs 351 pg/mL, P<0.05);dose-dependent inhibition of myogenesis,↓ GLUT4 translocation (20–25%),↓ ATP (30%)	Direct evidence for GLP-1–mediated impairment of glucose uptake and energy metabolism, supporting gut–muscle axis hypothesis.