Effect of Semaglutide on Thigh Skeletal Muscle Volume, Fat Infiltration and Physical Function in People With Obesity: Secondary Analysis of STEP UP.

AIMS: To assess the effect of semaglutide on body composition and physical function. MATERIALS AND METHODS: The phase 3b STEP UP trial randomised adults with body mass index ≥ 30 kg/m2 to once-weekly subcutaneous semaglutide 7.2 mg, semaglutide 2.4 mg or placebo for 72 weeks. This prespecified secondary analysis assessed changes in MRI body composition and physical function. RESULTS: Of 1407 participants, 55 with a valid baseline scan were included (semaglutide 7.2 mg, n = 43, 2.4 mg, n = 6 [pooled semaglutide group, n = 49]; placebo, n = 6). Estimated treatment differences (95% confidence intervals; p-values) for absolute changes in adipose/muscle compartment volumes for the pooled semaglutide versus placebo group, respectively, were: -11.1 L (-16.5 to -5.7; p < 0.0001) for adipose body tissue, -1.5 L (-2.9 to -0.1; p = 0.04) for visceral adipose tissue, -1.7 L (-4.0 to 0.7; p = 0.16) for lean body tissue, -1.1 L (-2.3 to 0.1; p = 0.07) for thigh skeletal muscle volume and -0.92%-points (-1.41 to -0.42; p = 0.001) for thigh muscle fat infiltration. Similar results were seen for relative changes in adipose/muscle compartment volumes. A sensitivity analysis for the semaglutide 7.2 mg group versus placebo showed similar results. A mean of 13 sit-to-stand repetitions in 30 s at baseline, and 15 repetitions at Week 72, was observed in the pooled semaglutide and placebo groups. CONCLUSIONS: Semaglutide plus lifestyle intervention was associated with reductions in adipose tissue volume, skeletal muscle volume and skeletal muscle fat infiltration, with a preserved number of sit-to-stand repetitions. Further research to assess the impact of weight loss on skeletal muscle composition and function should be explored in the future. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT05646706.