Longitudinal Changes in Body Composition, Adaptive Thermogenesis and Muscle Strength in Patients with Obesity Treated with Semaglutide

BACKGROUND: Obesity management increasingly emphasizes not only total weight reduction but also the quality of weight loss, reflecting the balance between fat and lean tissue changes, preservation of strength capacity, and changes in energy expenditure. Semaglutide is effective for weight management, yet its integrated real-world effects on body composition, resting energy expenditure (REE), adaptive thermogenesis and muscle strength in adults with obesity without diabetes remain incompletely characterized. METHODS: We performed a single-center, retrospective observational study in routine care at the Obesity Treatment Unit (UTIO), Hospital Universitari Vall d'Hebron (Barcelona, Spain), January 2024-December 2025. Adults (≥18 years) with obesity (BMI ≥30 kg/m²) and without diabetes were included if baseline (V1) and 12‑month (V2) data were available. Patients were classified as lifestyle educational program (n=39) or lifestyle educational program plus semaglutide (n=44), requiring ≥70% exposure during follow-up. Anthropometry, dominant handgrip strength, body composition by bioelectrical impedance analysis, and REE by indirect calorimetry were assessed at V1 and V2. Musculoskeletal remodeling was evaluated using continuous, age and BMI-dependent Skeletal Muscle Index Standardized Deviation Scores (SMI-SDS) validated against gold-standard MRI data. Between-group differences were tested using ANCOVA or rank-ANCOVA with the absolute change from baseline (Delta [Δ]) as the dependent variable, adjusted for the baseline age, gender and body weight; partial eta squared (η²p) was reported. A study-specific predictive equation was derived to estimate REE and calculate adaptive thermogenesis (AT) from measured versus predicted REE at baseline and 12 months, with a external sensitivity analysis using the Ostendorf equation. RESULTS: Semaglutide group was associated with significantly greater 12‑month reductions in body weight (Δ -11.0 kg, p=0.001), BMI (Δ -4.0 kg/m², p=0.001) and waist circumference (Δ -7.0 cm, p=0.002) versus lifestyle group. WtHR showed a small, non-significant increase with lifestyle group (Δ +0.01) versus a significant decrease in semaglutide group (Δ -0.04); the between-group difference was statistically significant after covariate adjustment (p<0.001). Bioelectrical impedance analysis showed significant reductions in adiposity (including fat mass and indicative visceral fat area trends) in semaglutide group skeletal muscle mass (SMM) and fat-free mass (FFM) also decreased in the semaglutide group (SMM=29.9 to 28.7 kg; FFM=53.8 to 52.7 kg; p<0.001). Crucially, reference-based muscle evaluation revealed a highly significant structural improvement in SMI-SDS selectively in semaglutide group (delta 0.52 vs. 0.09 in lifestyle group; adjusted p<0.001), demonstrating qualitative muscle mass optimization despite absolute lean tissue loss. Absolute handgrip strength was preserved in both groups, while relative handgrip strength improved with semaglutide (adjusted p=0.003; η²p=0.110). REE decreased in both groups; the adjusted analyses identified a p value at the limit of statistical significance (adjusted p=0.050; η²p=0.049). The AT analysis showed that part of this decline exceeded what would be expected from changes in FM, FFM, age, and gender. However, the magnitude of AT did not differ significantly between semaglutide group (delta AT: -210.2 kcal/day) and lifestyle group (delta AT: -373.4 kcal/day). RQ showed no differences between groups in terms of preference for fat oxidation. CONCLUSION: In routine obesity care, semaglutide was associated with reductions in total adiposity and improvements in central anthropometric markers. Absolute handgrip strength was preserved in both groups. Crucially, reference-based muscle evaluation revealed a highly significant structural improvement in SMI-SDS selectively in semaglutide group. AT in both groups showed a decline in REE beyond that expected from FFM, FM, age, and gender, with no significant between-group differences. Comprehensive monitoring with body composition, handgrip strength, and indirect calorimetry may enhance follow-up of patients receiving obesity management medication.