<p>Semaglutide has demonstrated beneficial effects in patients with type 2 diabetes; however, its long-term impact on skeletal muscle remains uncertain, particularly in individuals with multiple risk factors for muscle decline. We report a case of a 65-year-old man with type 2 diabetes who developed progressive proximal muscle weakness and was subsequently diagnosed with spinal and bulbar muscular atrophy (SBMA), for which leuprorelin therapy was initiated. Following treatment initiation, he exhibited worsened glycemic control, increased body weight and fat mass, along with reductions in both skeletal muscle mass and strength. At the age of 72, oral semaglutide was introduced. Over the following two years, improvements in glycemic parameters and reductions in fat mass were observed. Importantly, skeletal muscle mass and strength were relatively preserved, with only a minor annual decrease in muscle mass (− 0.1&#xa0;kg/year), consistent with changes reported in previous studies of semaglutide-treated patients without neuromuscular conditions. To our knowledge, this is the first reported case describing the use of semaglutide in a patient with diabetes and SBMA under leuprorelin treatment, suggesting the potential utility of GLP-1 receptor agonists in managing metabolic parameters in individuals at high risk for muscle decline.</p>