AIMS: GLP-1 receptor agonists (GLP-1RAs) are first-line therapies for type 2 diabetes (T2DM) due to their additional weight-lowering and cardiovascular benefits. However, their impact on muscle mass is debated, posing a concern for sarcopenia in older adults with T2DM. This systematic review and meta-analysis aimed to evaluate the effects of GLP-1RAs on body composition and sarcopenia-related markers in diabetic patients and relevant preclinical models, and to explore the underlying mechanisms.
METHODS: We systematically searched PubMed, Web of Science, MEDLINE, Cochrane Library, and EMBASE to identify relevant randomized controlled trials and animal studies on the impact of GLP-1 RAs on muscle in diabetic participants. Standardized Mean Difference (SMD) or Mean Difference (MD) with 95 % confidence intervals (CI) were calculated using random-effects or fixed-effect models to synthesize the effects on anthropometric, functional, and molecular endpoints.
RESULTS: A total of 254 articles were retrieved, yielding 18 eligible studies after screening against the inclusion criteria. These comprised six human studies measuring lean mass, four clinical trials assessing Skeletal Muscle Mass Index (SMI), and eight animal studies. The animal studies investigated parameters including muscle mass, muscle fiber cross-sectional area, grip strength, lean mass percentage, myogenin, MyoD, Atrogin-1, MuRF-1, myostatin, GLUT4, SIRT1, and inflammatory cytokines (IL-1β, IL-6, TNF-α).
CONCLUSIONS: GLP-1 RAs were found to increase the percentage of lean body mass in animal models, improve body composition, enhance skeletal muscle strength, elevate concentrations of muscle growth factors, and reduce muscle growth inhibitory factors and inflammatory factors. These effects promote muscle cell proliferation and differentiation, accelerate muscle protein synthesis, leading to better overall muscle function. Confirming these promising preclinical findings requires large-scale randomized controlled trials in humans.
