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

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 <. 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 >. 07). The prevalence of slow gait speed (<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.