A large real-world study reveals how surgery and GLP-1 therapies reshape fat and lean tissue differently over time, also highlighting why sex and treatment choice matter for preserving muscle while losing weight.
Study: Body Composition Changes After Bariatric Surgery or Treatment With GLP-1 Receptor Agonists. Image credit: Lee Charlie/Shutterstock.com
In a recent study published in JAMA Network Open, researchers investigated changes in body composition following bariatric surgery or treatment with glucagon-like peptide 1 receptor agonists (GLP-1RAs) using real-world electronic health record data.
Obesity prevalence rises as treatment options expand
Obesity is a significant global public health concern. Estimates indicate that approximately 40 % of adults in the United States (US) had obesity in 2023, and projections forecast that nearly half of the US adult population will be obese by 2030. Obesity treatment can alleviate the disease burden and improve the quality of life.
Current treatments for obesity include pharmacological, surgical, and lifestyle interventions, with GLP-1RAs and bariatric surgery resulting in the most substantial weight loss. Although evidence on changes in body mass index (BMI) and body weight after GLP-1RA treatment or bariatric surgery is abundant, data on changes in body composition are limited, particularly outside of tightly controlled clinical trials. Changes in absolute body weight were not the primary focus of this analysis.
Retrospective analysis compares surgery and GLP-1 treatment trajectories
In the present study, researchers examined temporal changes in body composition over 24 months following treatment with GLP-1RAs or bariatric surgery in a retrospective, single-center cohort. The study included patients aged 18–65 years who underwent bariatric surgery and those treated with GLP-1RAs, such as tirzepatide and semaglutide, with available body composition measures. Patients were excluded if they had a history of congestive heart failure or end-stage kidney disease.
In addition, surgery patients who used tirzepatide or semaglutide within a year before or two years after surgery were excluded. To enrich the cohort for patients likely to require ongoing pharmacologic treatment, the GLP-1RA cohort was further restricted to individuals with at least two prescriptions or a minimum of 5 % weight loss. Electronic health records were accessed to retrieve information on demographics, surgery details, prescriptions, disease history, and baseline BMI.
Body composition was measured using bioelectrical impedance analysis (BIA) at baseline, before surgery or treatment initiation, and at multiple time points over the subsequent 24 months. The authors noted that BIA estimates total fat-free mass but cannot distinguish between skeletal muscle and other lean tissues, and may be influenced by hydration status and other physiological factors.
Relative reductions in fat-free mass (FFM) and fat mass (FM) from baseline were computed. Additionally, the FFM-to-FM ratio was calculated at each time point. The relative changes in FM, FFM, and the FFM-to-FM ratio were estimated at 6, 12, and 24 months using generalized linear mixed models. Finally, stratified analyses were performed by baseline BMI, sex, diabetes status, race, and GLP-1RA treatment duration.
Surgery leads to larger fat loss than GLP-1 therapy
The study included 1,257 patients undergoing bariatric surgery and 1,809 recipients of GLP-1RA, with an average age of 43.4 and 45.4 years, respectively. The mean baseline BMI was 46.8 kg/m² for the surgery group and 41 kg/m² for the GLP-1RA group. Most patients in both groups were female, White, and had hypertension. However, cardiometabolic comorbidities differed between groups at baseline, with diabetes more prevalent in the surgery group and dyslipidemia more common among GLP-1RA recipients.
In the surgery group, 58.4 % of patients underwent Roux-en-Y gastric bypass surgery, while the remainder underwent sleeve gastrectomy. In the GLP-1RA group, 91 % used semaglutide and 9 % used tirzepatide. The GLP-1RA group showed a higher FFM-to-FM ratio at baseline than the surgery group.
After both surgery and GLP-1RA treatment, FM showed a significant reduction over time, with the surgery group having a more pronounced decrease in this observational analysis. The mean relative FM reductions were 42.4 % at six months and 49.7 % at 12 and 24 months in the surgery group.
In the GLP-1RA group, the mean FM decreases were 10.3 % at six months, 17.3 % at 12 months, and 18 % at 24 months. FFM also decreased in both groups over time, with greater reductions in the surgery group. The mean relative FFM reductions were 7.8 %, 10.6 %, and 11.7 % for the surgery group and 1.8 %, 3 %, and 3.3 % for the GLP-1RA group at 6, 12, and 24 months, respectively.
In contrast, the FFM-to-FM ratio showed a significant increase in both groups over time, with greater increases in the surgery group. The FFM-to-FM ratios were 1.8, 2.1, and 2.0 in the surgery group at 6, 12, and 24 months, respectively. The GLP-1RA group had an FFM-to-FM ratio of 1.4 at six months and 1.5 at 12 and 24 months.
Similar trends of FM reductions and FFM-to-FM ratio increases were observed in subgroups defined by race, sex, diabetes status, GLP-1RA treatment duration, and baseline BMI. Nevertheless, changes in FFM varied by sex, males showed no significant reductions in FFM at six months in both groups, maintaining this preservation over time. In contrast, females showed substantial decreases in FFM in both groups, particularly after bariatric surgery.
Observational findings highlight need to preserve lean mass
Together, GLP-1RA treatment and bariatric surgery were associated with substantial FM loss, modest FFM reductions, and improved FFM-to-FM ratio over 24 months. Bariatric surgery was associated with greater relative changes than GLP-1RA treatment, although the authors caution that the study was not designed as a direct comparative effectiveness analysis. Moreover, males exhibited better FFM preservation than females.
Because the study relied on retrospective electronic health records, BIA-based body composition estimates, and lacked information on medication dosing, adherence, and downstream clinical outcomes, the findings should be interpreted with caution. Nonetheless, these results indicate a favorable shift in body composition and provide evidence to guide interventions that preserve FFM and promote fat loss in real-world obesity treatment settings, while highlighting the need for prospective studies using more precise body composition measures to confirm these patterns.
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Weight loss drugs and surgery improve body composition in patients with obesity