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

In 30 seconds

This prespecified secondary analysis of the phase 3b randomised STEP UP trial examined MRI body composition and physical function in adults with obesity assigned to weekly semaglutide or placebo for 72 weeks. Of 1407 trial participants, 55 had a valid baseline scan and were included. Compared with placebo, pooled semaglutide was associated with a greater reduction in adipose body tissue volume (estimated treatment difference −11.1 L; 95% CI −16.5 to −5.7; p < 0.0001). Thigh muscle fat infiltration also decreased, while thigh muscle volume changes were not statistically significant; sit-to-stand repetitions were preserved.

Key findings

• Pooled semaglutide reduced adipose body tissue volume versus placebo by an estimated −11.1 L (95% CI −16.5 to −5.7; p < 0.0001).
• Visceral adipose tissue decreased by −1.5 L (95% CI −2.9 to −0.1; p = 0.04) versus placebo.
• Thigh muscle fat infiltration decreased by −0.92%-points (95% CI −1.41 to −0.42; p = 0.001); thigh muscle volume change was not statistically significant.
• Mean sit-to-stand performance was 13 repetitions at baseline and 15 at Week 72 in both pooled semaglutide and placebo groups.

Why it matters

Weight-loss treatment can alter both adipose and muscle compartments, so body weight alone may not capture changes relevant to physical function. In this analysis, semaglutide was associated with reduced thigh muscle fat infiltration while sit-to-stand performance was maintained. These findings provide preliminary information about body composition during treatment, but do not establish the functional consequences of the observed tissue changes.

What to keep in mind

Only 55 of 1407 trial participants had a valid baseline scan and were included, with just six participants in each of the semaglutide 2.4 mg and placebo groups. The analysis was secondary, and follow-up was 72 weeks.