Author(s): MINDERIS, P., SVIDERSKIS, M., FOKIN, A., GRAY, S.R., RATKEVICIUS, A., Institution: LITHUANIAN SPORTS UNIVERSITY, Country: LITHUANIA, Abstract-ID: 1050

INTRODUCTION:
GLP-1 receptor agonists, such as semaglutide, are widely used in obesity treatment as these drugs induce substantial weight loss, primarily through appetite suppression. A growing number of athletes are using these drugs to optimise body composition. However, there are concerns that semaglutide-associated weight loss may induce greater muscle wasting, compared with traditional dietary interventions. The aim of the study was to compare the effects of semaglutide and caloric restriction on body composition and skeletal muscle mass in obese mice.
METHODS:
High-fat diet (HFD) fed obese 8-month-old male C57BL/6J mice were assigned either to a semaglutide (SEMA) (n=39) or caloric restriction (CR) (n=41) group for 28-days. CR group was matched by energy intake to SEMA group. A group of obese mice (OB) (n=9) continued to be fed HFD ad libitum and served as controls. Body mass was recorded daily. Body composition was assessed using bioimpedance spectroscopy, and major adipose depots and hindlimb skeletal muscles were weighed after dissection post mortem. Data were analysed using a two-way repeated-measures ANOVA to assess the effects of intervention, time, and their interaction, followed by appropriate post hoc tests.
RESULTS:
SEMA and CR groups exhibited similar reductions in energy intake compared to OB group (-25.6 ± 7.3 and -25.7 ± 2.8 vs. 3.9 ± 7.6%, P < 0.001) and had lower body mass post intervention (38.6 ± 4.2 and 39.5 ± 3.1 vs 49.1 ± 4.9 g, P < 0.001). From day 11 onwards, % body mass loss was greater in the SEMA group than in the CR group and remained so until the end of the intervention, resulting in a greater total weight loss (-19.7 ± 4.6 vs. -16.6 ± 2.4% from initial, P < 0.001). Total body water and intracellular water were reduced in both intervention groups compared with their initial values, with a more pronounced decrease observed in the SEMA group (P < 0.05). Despite these differences, post-mortem analysis of isolated muscle weights revealed no evidence of greater skeletal muscle loss in the SEMA group compared to CR group. Composite muscle mass index in the SEMA group was similar to CR (414.1 ± 17.9 and 427.3± 15.0 mg, P > 0.05) but lower compared to the OB group (435.2 ± 15.1 mg, P < 0.05). Composite fat mass was markedly reduced in both the SEMA and CR groups compared with the OB group (5.17 ± 1.25 and 5.87 ± 0.61 vs. 7.73 ± 1.00 g, P < 0.01).
CONCLUSION:
Semaglutide induces greater weight loss than caloric restriction, even when energy intake is similar, with no differences in the loss of skeletal muscle mass. These findings suggest that concerns regarding excessive muscle wasting with semaglutide may be overstated.