Objective To investigate the early changes in body weight and muscle mass in obese patients after treatment with laparoscopic sleeve gastrectomy (LSG) and tirzepatide.

Methods The single center real world retrospective cohort study was conducted. The clinical data of 520 obese patients who underwent LSG or received tirzepatide treatment (≥3 months) at West China Hospital of Sichuan University from January to July 2025 were collected. There were 129 males and 391 females, aged (33±9) years. Of 520 patients, 407 patients undergoing LSG were set as the surgical group and 113 patients receiving tirzepatide treatment were set as the tirzepatide group. Observation indicators: (1) clinical efficacy of two groups of patients followed up for 3 months; (2) clinical efficacy of two groups of patients followed up for 6 months; (3) analysis of interaction effects between two groups of patients; (4) analysis of response to weight loss in two groups of patients. Comparison of measure-ment data with normal distribution between groups was conducted using the independent sample t test. Comparison of count data between groups was conducted using the chi‑square test or Fisher exact probability. The longitudinal repeated measurement data from the follow-up period, including baseline data, data at time of 3 month and 6 month, were analyzed using the linear mixed model. The baseline age and body mass index (BMI) were included as covariates in the model for adjustment to eliminate potential indication bias. In the fixed effects model, group, time, and the interaction term between group and time (group×time) were included as fixed effects to evaluate the trend differences of different intervention methods over time. The pairwise comparisons based on estimated marginal means were used for intergroup differences (time point at 3 and 6 month during follow-up), and the Bonferroni method was used for significance correcting. The adjusted mean difference was defined as the difference between the surgical group and the tirzepatide group.

Results (1) Clinical efficacy of two groups of patients followed up for 3 months: during the follow-up time of 3 months, there were 204 patients in the surgical group and 74 patients in the tirzepatide group achieved effective follow‑up. The total weight loss percentage (%TWL) were 18.7%±0.4% in the surgical group versus 12.0%±0.6% in the tirzepatide group, the body were (76.0±0.4) kg versus (84.2±0.7) kg, the BMI were (27.20±0.18) kg/m² versus (28.70±0.31) kg/m², the fat mass were (31.24±0.23) kg versus (32.57±0.35) kg, the skeletal muscle mass loss percentage were 10.8%±0.4% versus 8.2%±0.6%, the skeletal muscle mass/body fat mass ratio were 1.06±0.02 versus 0.99±0.03, the Δskeletal muscle mass/body fat mass ratio were 0.40±0.02 versus 0.32±0.03, respectively, showing significant differences in the above indicators between the two groups (P<0.05). (2) Clinical efficacy of two groups of patients followed up for 6 months: during the follow-up time of 6 months, there were 104 patients in the surgical group and 23 patients in the tirzepatide group achieved effective follow‑up. The %TWL were 24.3%±0.5% in the surgical group versus 16.0%±0.8% in the tirzepatide group, the body were (70.9±0.5) kg versus (80.2±1.0) kg, the BMI were (25.32±0.21) kg/m² versus (27.46±0.41) kg/m², the fat mass were (30.16±0.30) kg versus (31.23±0.47) kg, the skeletal muscle mass loss percentage were 10.4%±0.4% versus 7.7%±0.7%, the skeletal muscle mass/body fat mass ratio were 1.28±0.02 versus 1.12±0.04, the Δskeletal muscle mass/body fat mass ratio were 0.61±0.02 versus 0.43±0.04, respectively, showing significant differences in the above indicators between the two groups (P<0.05). (3) Analysis of interaction effects between two groups of patients: there were significant group‑by‑time interaction effects for %TWL, body weight, BMI, skeletal muscle mass/body fat mass ratio and Δskeletal muscle mass/body fat mass ratio between the surgical group and tirzepatide group at the follow‑up time of 3 months and 6 months, respectively (F_interaction=4.55, 59.56, 76.90, 3.40, 4.58, P<0.05). (4) Analysis of response to weight loss in two groups of patients: at the follow‑up time of 3 months, cases with %TWL as <5%, ≥5%, ≥10%, ≥15% and ≥20% were 2,202, 199, 173, 77 in the 204 patients of the surgical group versus 5, 69, 51, 21, 4 in the 74 patients of the tirzepatide group, respectively, showing significant differences in response to different %TWL between the two groups (P<0.05). At the follow‑up time of 6 months, cases with %TWL as <5%, ≥5%, ≥10%, ≥15% and ≥20% were 0, 104, 103, 99, 80 in the 104 patients of the surgical group versus 1, 22, 18, 16, 4 in the 23 patients of the tirzepatide group, respectively, showing no significant difference in response to <5% and ≥5% of %TWL between the two groups (P>0.05) and significant differences in response to ≥10%, ≥15% and ≥20% of %TWL between the two groups (P<0.05).

Conclusion The early effects of weight loss and body fat improvement of LSG are superior to those of tirzepatide, and the skeletal muscle loss caused by both treatment methods is proportional to the overall weight loss, with no difference in tissue selectivity of adipose and skeletal comsumption.