Surgery Beats GLP-1 Drugs for Fat Loss, Muscle Retention, Study Suggests

 

• Bariatric surgery patients and GLP-1 medication users had fat-mass reductions of 49.7% and 18%, respectively, after 2 years.
• Surgery led to higher fat-free mass to fat-mass ratios, suggesting more muscle, bone, and water relative to body fat.
• Researchers said a higher fat-free mass to fat-mass ratio might help reduce mortality risk.

Bariatric surgery and GLP-1 receptor agonists both reduced fat mass over 2 years of treatment, but surgery was associated with a more favorable body composition, a cohort study indicated.

By month 24, the covariate-adjusted mean fat-mass reductions were 49.7% (95% CI 47.8-51.5) among bariatric surgery patients and 18% (95% CI 16.4-19.7) among users of GLP-1 drugs for either type 2 diabetes treatment or weight loss, found Jason M. Samuels, MD, of Vanderbilt University Medical Center in Nashville, Tennessee, and colleagues.

Both groups also saw significant relative reductions in other components of body mass, averaging 11.7% (95% CI 10.4-12.9) after bariatric surgery and 3.3% (95% CI 2.1-4.4) with GLP-1 drugs when it came to reductions in fat-free mass, the researchers reported in JAMA Network Open.

While fat-free mass to fat-mass ratios significantly increased in both groups -- denoting improved body composition -- bariatric surgery patients maintained a higher ratio than GLP-1 agonist users through the 2-year follow-up (2.0 vs 1.5).

"Bariatric surgery and GLP-1 receptor agonist medications are currently the most effective weight-loss interventions for people with obesity, especially for those with severe obesity and comorbidities such as type 2 diabetes, sleep apnea, dyslipidemia, and CVD [cardiovascular disease]," the authors noted.

Although both are efficacious, bariatric surgery and GLP-1 medications' differing impact on body composition shouldn't be overlooked, Samuels and team underscored. "Growing evidence suggests that FM [fat mass] and FFM [fat-free mass] may have distinct and often opposing effects on mortality."

In a study of healthy Danish adults followed over nearly two decades, greater fat mass and lower fat-free mass were both independently linked to increased early mortality, they noted. "Similarly, a 22-year prospective study of 787 older Swedish men found that FM percentage was positively associated with all-cause mortality, while FFM percentage was inversely associated with all-cause mortality."

Sarcopenic obesity, characterized by greater adipose tissue and lower muscle mass, is also "a growing concern," the authors added. "Sarcopenic obesity has been associated with elevated all-cause mortality, CVD incidence and mortality, and risks of metabolic syndrome, type 2 diabetes, dyslipidemia, and depressive symptoms."

"Collectively, these findings underscore the importance of obesity treatments that maximize FM reduction while maintaining and ideally enhancing the FFM to FM ratio," they wrote.

The single-center cohort study included 3,066 patients who underwent first-time bariatric surgery from November 2017 to July 2022 or were treated with semaglutide (Ozempic, Wegovy) or tirzepatide (Mounjaro, Zepbound) from November 2018 to December 2023. The analysis couldn't account or adjust for GLP-1 dosage (which is lower when used for type 2 diabetes treatment) or for adherence.

Bariatric surgery patients underwent Roux-en-Y gastric bypass (58.4%) or sleeve gastrectomy (41.6%). Most GLP-1 agonist users took semaglutide versus tirzepatide (91% vs 9%).

Of the 1,257 surgical patients, average age was 43 years and baseline body mass index (BMI) was 46.8. Most (82%) were women, and 79% were white. Of the 1,809 GLP-1 agonist users, average age was 45 years, BMI was 41, 81% were women, and 68% were white.

Diabetes was less common in the GLP-1 agent group (29.4% vs 34.6% in the surgery group), while hypertension and dyslipidemia were more common (74.2% vs 70% and 47.9% vs 42.2%, respectively).

Subgroup analyses showed similar reductions in fat mass and increases in fat-free mass to fat-mass ratio in groups divided by sex, race, baseline BMI, history of diabetes, and GLP-1 therapy duration.

Male patients had better preservation of fat-free mass compared with female patients, especially after GLP-1 treatment.

Body composition was measured by bioelectrical impedance analysis, which is more practical and noninvasive, but less precise than other measures like dual-energy x-ray absorptiometry, CT, or MRI.

"We also did not evaluate the associations between changes in body composition and clinical health outcomes, such as metabolic improvements or quality-of-life measures," Samuels and co-authors acknowledged.

Disclosures

The study was supported in part by grants from the National Institutes of Health. The Vanderbilt Institute for Clinical and Translational Research is funded by the National Center for Advancing Translational Sciences Clinical Translational Science Award Program.

Samuels reported no disclosures. Co-authors reported relationships with Intuitive Surgical, Novo Nordisk, Eli Lilly, Quest Diagnostics, and Rhythm.

Primary Source

JAMA Network Open

Source Reference: Wang Z, et al "Body composition changes after bariatric surgery or treatment with GLP-1 receptor agonists" JAMA Netw Open 2026; DOI: 10.1001/jamanetworkopen.2025.53323.

https://www.medpagetoday.com/endocrinology/obesity/119354