Effect of Semaglutide on Measured vs Estimated Glomerular Filtration Rate

BACKGROUND AND HYPOTHESIS: Semaglutide is a glucagon-like peptide-1 receptor agonist widely used for its glucose-lowering effects in people with type 2 diabetes (T2D), as well as its cardiovascular and kidney-protective properties. However, it remains unclear whether semaglutide influences blood concentrations of endogenous filtration markers like creatinine, cystatin C, beta-trace protein (BTP), and beta-2 microglobulin (B2M). We investigated the effect of semaglutide on these filtration markers and the performance of estimated glomerular filtration rate (eGFR) equations compared with measured glomerular filtration rate (mGFR). METHODS: Post hoc analysis of a randomized, double-blind, placebo-controlled clinical trial. Individuals with T2D and albuminuria were randomized in a 1:1 ratio to receive semaglutide 1 mg weekly or matching placebo for 26 weeks on top of empagliflozin. mGFR was determined by 99m-Tc-DTPA plasma clearance and eGFR was calculated using CKD-EPI equations based on plasma creatinine (eGFRcre), cystatin C (eGFRcys), their combination (eGFRcomb), or a panel of creatinine, cystatin C, BTP, and B2M (eGFRpanel). Outcomes included change in filtration marker concentration, mGFR, and eGFR from baseline to end-of-treatment, as well as eGFR performance compared to mGFR at each timepoint. RESULTS: Among 48 participants (median age 70 years; 16.7% female), semaglutide treatment was associated with a small but significant increase in plasma creatinine and BTP compared with placebo, whereas there was no significant change in cystatin C or B2M. Semaglutide treatment was not associated with a significant change in mGFR (median [IQR] change of 0 [-7.5 to 10.3] mL/min/1.73 m2) compared with placebo (median [IQR] change of -2 [-11.3 to 3.0] mL/min/1.73 m2). Both eGFRcre and eGFRcys were consistently outperformed by eGFRcomb and eGFRpanel at baseline and end-of-treatment. CONCLUSION: Semaglutide treatment was associated with a small increase in plasma creatinine and BTP but not cystatin C or B2M, and eGFRcomb yielded the most reliable estimates of mGFR.