Semaglutide 2.4 mg/wk reduces fat and lean mass in CKD patients without affecting eGFR correlation
Background
Patients with chronic kidney disease (CKD) often experience overweight or obesity, which exacerbates kidney function decline. The glucagon-like peptide-1 receptor (GLP-1R) agonist semaglutide is known to reduce body weight, blood pressure (BP), and slow glomerular filtration rate (GFR) decline. However, semaglutide can influence serum creatinine and cystatin C levels through non-renal mechanisms, potentially confounding estimated GFR (eGFR). This study aimed to clarify the relationship between semaglutide-induced changes in body composition and actual GFR measurements.
Study Design
This was a prespecified analysis of a randomized, placebo-controlled, double-blind clinical trial involving 101 adults with CKD and overweight or obesity, specifically excluding type 2 diabetes. Participants were randomized to receive semaglutide 2.4 mg/wk subcutaneously or matched placebo for 24 weeks. Researchers measured GFR using iohexol clearance (mGFR), estimated GFR using creatinine and cystatin C (eGFR), and determined lean body mass, fat mass, and extracellular water via bioimpedance spectroscopy.
Results
After 24 weeks, semaglutide treatment significantly reduced total body weight, lean body mass, and fat mass compared to placebo. Total body weight decreased by -9.1 kg (95% CI, -11.0 to -7.2). Lean body mass changed by -2.5 kg (95% CI, -6.6 to 1.6), and fat mass by -3.9 kg (95% CI, -7.8 to 0.0). Importantly, no significant correlations were observed between changes in total body weight, lean body mass, or fat mass with changes in eGFR (creatinine or cystatin C) or mGFR during semaglutide treatment (all Spearman correlation coefficients <0.23). Similar results were confirmed in multivariable adjusted analyses. Semaglutide also significantly reduced extracellular water by -0.9 L (95% CI, -1.6 to -0.1) and systolic BP by -6.3 mm Hg (95% CI, -10.9 to -1.7). Changes in BP were found to correlate with changes in extracellular water.
Semaglutide treatment led to a significant 9.1 kg reduction in total body weight over 24 weeks compared to placebo.
Key Findings
- Semaglutide reduced total body weight by 9.1 kg (95% CI, -11.0 to -7.2) over 24 weeks.
- Fat mass decreased by 3.9 kg (95% CI, -7.8 to 0.0) and lean body mass by 2.5 kg (95% CI, -6.6 to 1.6).
- No correlation was found between changes in body composition and changes in
eGFRormGFR(Spearman coefficients <0.23). - Extracellular water decreased by 0.9 L (95% CI, -1.6 to -0.1), and systolic BP by 6.3 mm Hg (95% CI, -10.9 to -1.7).
Why It Matters
This study provides crucial clarity for clinicians and individuals using semaglutide, particularly those with CKD. It demonstrates that while semaglutide effectively reduces both fat and lean body mass, these body composition changes do not confound eGFR or mGFR measurements. Clinicians can interpret GFR changes in patients on semaglutide with greater confidence, understanding that observed kidney function improvements or stabilization are likely direct effects or systemic benefits, rather than artifacts of weight loss-induced changes in creatinine or cystatin C. This supports the use of semaglutide in CKD management without concerns that body composition shifts will obscure true renal effects, reinforcing its role in a comprehensive treatment protocol.
semaglutide
ckd
obesity
body composition
gfr
weight loss