Semaglutide Promotes Fat Loss While Preserving Muscle Function in Severe Obesity
Key Clinical Summary
- In the SEMALEAN study, semaglutide 2.4 mg weekly produced significant weight loss in a real-world cohort (n = 106), with mean reductions of 9.8% at 7 months and 12.7% at 12 months; 59% of patients lost ≥10% of body weight and 26% lost ≥15%.
- Fat mass decreased substantially, while lean mass declined modestly early but stabilized, resulting in a higher relative proportion of lean mass over time.
- Muscle function improved, with increased handgrip strength and reduced sarcopenic obesity prevalence (49% to 33%), suggesting semaglutide may support weight loss while preserving functional muscle health.
Treatment with semaglutide produces substantial weight loss while improving muscle function and reducing rates of sarcopenic obesity, according to findings from a study published in Diabetes, Obesity and Metabolism.
Obesity is a major global health challenge linked to numerous comorbidities, including type 2 diabetes, cardiovascular disease, sleep apnea, osteoarthritis, and several cancers. While lifestyle changes and bariatric surgery remain foundational treatments, pharmacologic therapies like glucagon-like peptide-1 (GLP-1) receptor agonists have transformed obesity management. Semaglutide is administered once weekly at a dose of 2.4 mg and has demonstrated weight loss exceeding 15% in many clinical trials. However, limited evidence exists on how this therapy affects body composition, including lean muscle mass and muscle function.
To address this gap, investigators conducted the SEMALEAN study, a prospective real-world cohort study at Rouen University Hospital in France. “The SEMALEAN study aims to investigate the effects of semaglutide on body composition, focusing on lean mass and muscle function over 1 year of treatment,” explained Mathieu Allissou, MD, Department of Nutrition and CIC-CRB 1404, CSO Rouen Normandie, CHU Rouen in Rouen, France, and coauthors.
A total of 106 patients completed the study after 9 early discontinuations due mainly to gastrointestinal side effects. Participants were predominantly women (68.9%), with a mean age of 52 years, average body weight of 127 kg, and mean BMI of 46.3 kg/m2. Many had obesity-related conditions, including liver steatosis (91.5%), obstructive sleep apnea (75.5%), hypertension (65.1%), and type 2 diabetes (35.8%). Nearly half of the participants (49%) had sarcopenia at baseline.
Over 12 months, semaglutide treatment produced significant weight loss. Average body weight declined by 9.8% at 7 months and 12.7% at 12 months, with 59% of patients losing at least 10% of body weight and 26% losing at least 15%. Body composition analysis showed that fat mass decreased by 14.3% at 7 months and 18.9% at 12 months, including substantial reductions in visceral fat. Although lean mass declined modestly early in treatment (−3.0 kg by month 7), it stabilized thereafter, and the relative proportion of lean mass increased as overall weight fell.
Importantly, muscle function improved. Handgrip strength increased by 3.7 kg at 7 months and 4.1 kg at 12 months, and the prevalence of sarcopenic obesity declined from 49% at baseline to 33% after 1 year. About 22% of patients who were sarcopenic at baseline no longer met criteria after treatment. Researchers also observed metabolic changes, including an initial drop in resting energy expenditure followed by partial recovery by month 12.
“In conclusion, the SEMALEAN study highlights the impact of semaglutide on obesity management, addressing not only weight loss but also lean mass, muscle function, and metabolic efficiency,” concluded the study authors.
Reference
Alissou M, Demangeat T, Folope V, et al. Impact of semaglutide on fat mass, lean mass and muscle function in patients with obesity: the SEMALEAN study. Diabetes Obes Metab. 2026;28(1):112-121. doi:10.1111/dom.70141
