JAMA Netw Open. 2026 Jan 2;9(1):e2553323. doi: 10.1001/jamanetworkopen.2025.53323.
ABSTRACT
IMPORTANCE: The association of bariatric surgery and newer glucagon-like peptide-1 receptor agonists (GLP-1RAs; semaglutide and tirzepatide) with body composition still lack evidence from clinical settings.
OBJECTIVE: To examine temporal changes in fat-free mass (FFM), fat mass (FM), and FFM to FM ratio after bariatric surgery or GLP-1RA treatment over 24 months.
DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used electronic health records from Vanderbilt University Medical Center of 1257 patients aged 18 to 65 years who underwent first-time bariatric surgery from November 21, 2017, to July 21, 2022, without GLP-1RA treatment from 1 year before to 2 years after surgery, and 1809 nonsurgical patients who started semaglutide or tirzepatide between November 12, 2018, and December 6, 2023, with 2 or more prescriptions or 5% or more weight loss. All patients had 2 or more bioelectrical impedance analysis measures and no history of end-stage kidney disease or congestive heart failure.
EXPOSURES: Bariatric surgery or GLP-1RA (semaglutide or tirzepatide) treatment.
MAIN OUTCOMES AND MEASURES: Relative changes in FFM, FM, and FFM to FM ratio over 24 months, controlling for age, sex, race, baseline body mass index (BMI), diabetes history, treatment year, time (restricted cubic splines), and time spline-by-treatment interaction.
RESULTS: The study comprised 3066 patients: 1257 in the surgery group (mean [SD] age, 43.4 [10.3] years; mean [SD] baseline BMI, 46.8 [7.1]; 1033 women [82.2%]) and 1809 in the GLP-1RA group (mean [SD] age, 45.4 [11.3] years; mean [SD] baseline BMI, 41.0 [7.9]; 1457 women [80.5%]). Adjusted mean relative FM reductions in the surgery group were 42.4% (95% CI, 41.5%-43.2%) at 6 months, 49.7% (95% CI, 48.8%-50.6%) at 12 months, and 49.7% (95% CI, 47.8%-51.5%) at 24 months; reductions in the GLP-1RA group were 10.3% (95% CI, 9.5%-11.0%) at 6 months, 17.3% (95% CI, 16.5%-18.1%) at 12 months, and 18.0% (95% CI, 16.4%-19.7%) at 12 months. Adjusted mean relative FFM reductions in the surgery group were 7.8% (95% CI, 7.2%-8.4%) at 6 months, 10.6% (95% CI, 10.0%-11.2%) at 12 months, and 11.7% (95% CI, 10.4%-12.9%) at 24 months; reductions in the GLP-1RA group were 1.8% (95% CI, 1.3%-2.4%) at 6 months, 3.0% (95% CI, 2.4%-3.5%) at 12 months, and 3.3% (95% CI, 2.1%-4.4%) at 24 months. FFM to FM ratios increased significantly in both groups, with surgical patients maintaining a higher ratio throughout: the FFM to FM ratios in the surgery group were 1.8 (95% CI, 1.8-1.8) at 6 months, 2.1 (95% CI, 2.1-2.1) at 12 months, and 2.0 (95% CI, 2.0-2.1) at 24 months; the FFM to FM ratios in the GLP-1RA group were 1.4 (95% CI, 1.4-1.4) at 6 months, 1.5 (95% CI, 1.4-1.5) at 12 months, and 1.5 (95% CI, 1.5-1.6) at 24 months. Similar trends were observed in stratified analyses by sex, race, baseline BMI, baseline diabetes status, and GLP-1RA treatment duration, although men showed better FFM preservation than women, especially after GLP-1RA treatment.
CONCLUSIONS AND RELEVANCE: In this single-center cohort study, both bariatric surgery and semaglutide or tirzepatide treatment were associated with substantial FM loss, moderate FFM loss, and improved FFM to FM ratio. These findings provide evidence to guide interventions aimed at preserving FFM while promoting fat loss.
PMID:41511769 | DOI:10.1001/jamanetworkopen.2025.53323