Effects of Semaglutide on Body Composition and GFR
Year: 2026
Type: article
Abstract: KEY POINTS: Treatment with semaglutide compared with placebo for 24 weeks reduced lean body mass and fat mass in adults with CKD and overweight or obesity. Changes in lean body mass or fat mass during semaglutide treatment did not correlate with changes in creatinine or cystatin C‑eGFR or measured GFR. Semaglutide significantly reduced extracellular water and BP, and changes in BP correlated with extracellular water. BACKGROUND: The glucagon-like peptide-1 receptor agonist semaglutide reduces hemoglobin A1c, body weight, BP, and GFR decline. Semaglutide may influence serum creatinine and cystatin C levels by nonkidney-related mechanisms and thereby affect eGFR. We studied the relationship between changes in body composition, eGFR and measured GFR (mGFR), and BP during semaglutide treatment. METHODS: We performed a prespecified analysis of a randomized placebo-controlled double-blind clinical trial in 101 adults with CKD with overweight status or obesity and without type 2 diabetes. Participants were randomized to 24 weeks of semaglutide 2.4 mg/wk subcutaneously or matched placebo treatment. We measured GFR with iohexol clearance, estimated GFR with creatinine and cystatin C, and used bioimpedance spectroscopy to determine lean body mass, fat mass, and extracellular water. RESULTS: After 24 weeks of treatment, semaglutide compared with placebo changed total body weight, lean body mass, and fat mass by -9.1 (95% confidence interval [CI], -11.0 to -7.2), -2.5 (95% CI, -6.6 to 1.6), and -3.9 (95% CI, -7.8 to 0.0) kg, respectively. No correlations were present between changes in total body weight, lean body mass, and fat mass with changes in eGFR (creatinine or cystatin C) or mGFR during semaglutide treatment (all Spearman correlation coefficients <0.23). Similar results were observed in multivariable adjusted analyses. Semaglutide compared with placebo changed extracellular water and systolic BP by -0.9 (95% CI, -1.6 to -0.1) L and -6.3 (95% CI, -10.9 to -1.7) mm Hg, respectively. Systolic BP changes during semaglutide treatment correlated with extracellular water changes (Spearman correlation 0.40; P = 0.005). CONCLUSIONS: Semaglutide reduced lean body mass and fat mass in patients with CKD with overweight status or obesity. These changes did not correlate with changes in creatinine or cystatin C eGFR or mGFR, suggesting that body weight reductions of 10% with semaglutide do not influence GFR estimates. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: ClinicalTrials.gov, NCT04889183 .
Authors: Hiddo J.L. Heerspink, Maria Soler, Jelle M. Beernink, Niels Jongs, Secundino Cigarran, Josep M. Cruzado, Maria Jesús Puchades, Marina López-Martínez, Ellen Apperloo, Femke Waanders, Gozewijn D. Laverman, Annemarie van der Aart-van der Beek, André P. van Beek, Jacobien C. Verhave, Sofia B. Ahmed, Roland E. Schmieder, Christoph Wanner, David Z.I. Cherney, José L. Górriz
Institutions: University Medical Center Groningen, University of Groningen, UNSW Sydney, The George Institute for Global Health, Vall d'Hebron Institut de Recerca, Vall d'Hebron Hospital Universitari, Bellvitge University Hospital, Institut d'Investigació Biomédica de Bellvitge, Universitat de Barcelona, Universitat de València, Isala, Ziekenhuis Groep Twente, Martini Ziekenhuis, Rijnstate Hospital, University of Alberta, Women and Children’s Health Research Institute, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen, Universitätsklinikum Würzburg, University of Toronto, Toronto General Hospital
Language: English
Subfield: Nephrology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funder: Novo Nordisk
OpenAlex ID: W7160087142