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

To assess the effect of semaglutide on body composition and physical function.

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.

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.

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.

ClinicalTrials.gov identifier NCT05646706.