Effects of Semaglutide on Body Composition and GFR: A Prespecified Analysis of the SMART Trial

Funding and conflicts

Funding

Novo Nordisk (investigator-initiated, per PubMed grant field)

Industry funded

Yes

Manufacturer

Novo Nordisk

Sponsor role

Funder; investigator-initiated (verify).

Author conflicts

Disclosure forms available with the article.

Independent replication

unknown

Notes

Authors declare relationships with the drug's manufacturer: Novo Nordisk

Funding is shown on every study and never used to score it.

Claims this study bears on

• GLP-1 receptor agonist therapy provides a net clinical benefit to healthy normal-weight adults aged 55-75.Contradicts

  Lean mass fell alongside fat mass with semaglutide even in a modest-weight CKD population.

• GLP-1 receptor agonists protect kidney function in people without diabetes.Mixed

  SMART: semaglutide reduced lean and fat mass; GFR estimates unaffected by body-composition change (n=101, 24 weeks).

• GLP-1-induced weight loss causes clinically meaningful loss of muscle mass or function.Supports

  Semaglutide reduced lean body mass (-2.5 kg vs placebo, not statistically significant) alongside fat mass in CKD with overweight/obesity.

The source, as retrieved

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 .

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