Background:
Semaglutide, a GLP-1 receptor agonist, is a highly effective medication for decreasing weight and weight complications by suppressing appetite, improving insulin signaling, and reducing intrahepatic triglycerides (IHTG). However, concomitant loss of muscle mass often accompanies weight loss, which may have consequences on muscle function. The purpose of this analysis was to examine changes in muscle quality, quantity, and function among people with HIV (PWH) treated with semaglutide for metabolic-associated steatotic liver disease (MASLD).
Methods:
We leveraged data from the SLIM LIVER (ACTG A5371) study, a single-arm pilot of the effects of semaglutide on IHTG in PWH with MASLD. Participants received subcutaneous semaglutide for 24 weeks (titrated to 1 mg/week by week 4). Psoas volume/fat fraction were assessed from liver magnetic resonance imaging and physical function by 10-time chair rise test and 4m gait speed, at baseline and week 24. Mean change from baseline was estimated with linear regression modeling and associations with Spearman’s correlations.
Results:
51 PWH enrolled; muscle measures were available from 46 participants. The mean age was 50 (standard deviation [SD] 11) years and BMI 35.5 (5.6) kg/m², 43% were women, 33% Black, and 39% Hispanic/Latino. Psoas muscle volume decreased by 9.3% (95% confidence interval [CI]: -13.4, -5.2; p<0.001) with an overall mean weight loss of -7.8 kg (CI: -9.5, -6.2) over 24 weeks. Decreases in psoas volume were greatest among PWH >60 years old (-22.8% [CI: -32.4, -13.3] vs -7.9% [CI: -12.3, -3.4]) in 40-60 and -2.4% [CI: -11.9, 7.2] in <40). No sex differences were observed. Reductions in psoas volume (%) correlated with decreases in IHTG (ρ=+0.32, p=0.028), BMI (ρ=+0.31, p=0.038), HbA1C (ρ=+0.39, p=0.007), and reduction in absolute volume was associated with reduction in fasting triglycerides (ρ=+0.33, p=0.027). Psoas muscle fat decreased by 0.42% (CI: -1.00, 0.17; absolute change), chair rise time improved by 0.73 seconds (CI: -1.4, 2.9) and gait speed improved by 0.05 m/sec (CI: -0.01, 0.10), though these changes did not reach statistical significance (p>0.078). The prevalence of slow gait speed (<1m/sec) decreased from 63% to 46% (p=0.029).
Conclusions:
In PWH using low-dose semaglutide for MASLD, muscle volume decreased, similar to volume changes seen in weight-loss interventions among overweight populations. The observed average improvement in muscle function suggests a beneficial effect of semaglutide on overall muscle quality.