Abstract
<title>Abstract</title> <p> <bold>Background</bold> Sarcopenia and impaired physical function are clinically relevant complications of chronic kidney disease (CKD). Patients with CKD and type 2 diabetes mellitus (T2DM) are particularly vulnerable to muscle impairment because of insulin resistance, inflammation, obesity, nutritional abnormalities, multimorbidity and reduced physical activity. Glucagon-like peptide-1 receptor agonists (GLP-1RA) are increasingly used in T2DM and CKD because of their metabolic, cardiovascular and kidney benefits. However, their impact on skeletal muscle mass, muscle strength and physical performance in moderate-to-advanced CKD remains insufficiently characterised. <bold>Methods</bold> MUSCLE-GLP1-CKD is a multicentre, prospective, real-world observational cohort study conducted in two tertiary nephrology departments in Tenerife, Spain. Adults with CKD stages 3a-4 and T2DM will be followed for 12 months in two parallel cohorts: patients initiating subcutaneous semaglutide according to routine clinical practice and comparable non-exposed controls receiving standard antidiabetic and cardiorenal care. Patients treated with other GLP-1RA may be included in broader secondary or sensitivity analyses when prescribed as part of standard care and when sample size allows. Study assessments will be performed at baseline, 6 months and 12 months. Body composition will be assessed by multifrequency segmental bioelectrical impedance analysis, including appendicular skeletal muscle mass index, fat mass, phase angle and extracellular water/total body water ratio. Muscle strength will be measured by handgrip dynamometry, and physical performance by the Short Physical Performance Battery and gait speed. SARC-F, IPAQ-short form and nutritional screening will characterise relevant confounders. The primary outcome is the between-group difference in 12-month change in appendicular skeletal muscle mass index. Secondary outcomes include changes in strength, physical performance, phase angle, sarcopenia status, kidney function, albuminuria and cardiometabolic variables. Renal, vascular and safety events will be exploratory. <bold>Discussion</bold> This study will generate prospective real-world evidence on muscle-health trajectories during GLP-1RA therapy in CKD and T2DM. The design combines a non-exposed comparator cohort, standardised functional assessment, routine clinical data and prespecified approaches to reduce confounding and time-related bias. <bold>Study registration</bold> The study will be registered in a publicly accessible registry before recruitment is completed and before any results are reported. </p>