The MUSCLE-GLP1-CKD study: design and rationale of a prospective real-world cohort evaluating muscle health after subcutaneous semaglutide initiation in chronic kidney disease and type 2 diabetes

Abstract Background 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. Semaglutide has established metabolic, cardiovascular and kidney benefits, but its effects on skeletal muscle quantity and function in moderate-to-advanced CKD remain insufficiently characterized. Methods MUSCLE-GLP1-CKD is a multicenter, prospective, real-world observational cohort study conducted in two tertiary nephrology departments in Tenerife, Spain. Adults with CKD stages 3a-4 and T2DM who are clinically eligible for semaglutide will be followed for 12 months. The primary comparison will include new users initiating subcutaneous semaglutide at the index date and eligible comparable patients who do not initiate any GLP-1 receptor agonist at that date. Patients treated with other GLP-1RA will be included in broader secondary or sensitivity analyses. Assessments at baseline, 6 months and 12 months will include multifrequency segmental bioelectrical impedance analysis, handgrip dynamometry, the Short Physical Performance Battery, gait speed, physical-activity and nutritional questionnaires, and routine renal and metabolic data. The primary outcome is the adjusted between-group difference in mean change in appendicular skeletal muscle mass index from baseline to 12 months, reported with a 95% confidence interval. Secondary outcomes include changes in muscle strength, physical performance, phase angle, sarcopenia status, body composition, kidney function, albuminuria and cardiometabolic variables. Kidney outcomes, cardiovascular events and treatment-related adverse events will be exploratory. Discussion This study will provide prospective real-world evidence on muscle-health trajectories after semaglutide initiation in CKD and T2DM. A contemporaneous non-initiator comparator, a symmetrical index date and prespecified confounding-control and sensitivity analyses are intended to improve interpretability while acknowledging the limitations of observational treatment comparisons. Trial registration The study was submitted for registration in the Spanish Registry of Clinical Studies (REec) through the Spanish Agency of Medicines and Medical Devices (AEMPS) GESTO platform on 16 August 2026 (GESTO identifier: 0116-2026-OBS; AEMPS No. 26–00131).