Abstract Background Semaglutide is highly effective for decreasing weight. Concomitant loss of muscle mass often accompanies weight loss and may have consequences on muscle function. Methods This is a secondary analysis from the SLIM LIVER (Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections, ACTG A5371) study, a single-arm study of semaglutide in people with human immunodeficiency virus (HIV, PWH) with metabolic dysfunction–associated steatotic liver diseases (MASLD). Participants received subcutaneous semaglutide for 24 weeks (titrated to 1 mg/week by week 4). Psoas volume and fat fraction were assessed from liver magnetic resonance imaging, and physical function was assessed by 10-time chair rise test and 4 m gait speed. Mean change from baseline to week 24 was estimated with linear regression modeling. Results Fifty-one PWH were enrolled (muscle measures n = 46). The mean age was 50 years (standard deviation, 11), body mass index was 35.5 kg/m2 (5.6), 43% were women, 33% Black, and 39% Hispanic/Latino. Psoas muscle volume decreased by 9.3% (95% confidence interval [CI]: −13.4 to −5.2; P &amp;lt; .001) over 24 weeks, but psoas muscle fat did not significantly change (−0.42%; 95% CI: −1.00 to .17; P = .16). Chair rise and gait speed showed nonsignificant improvements of 1.27 seconds (95% CI: −2.7 to .10) and 0.05 m/sec (95% CI: −.01 to .10), respectively (both P &amp;gt; .07). The prevalence of slow gait speed (&amp;lt;1 m/sec) decreased from 63% to 46% (P = .029). Conclusions In PWH receiving semaglutide for MASLD, despite decreased psoas muscle volume, there was no significant change in physical function, suggesting function was maintained despite significant loss of muscle. Clinical Trials Registration NCT04216589.

Effects of Semaglutide on Muscle Structure and Function in the SLIM LIVER Study